Abstract:
A heteroannelated anthraquinone derivative compound is provided. The heteroannelated anthraquinone derivative compound is represented by a formula (I): 
     
       
                 
         
             
             
         
       
     
     wherein R 1  is a substituent being one selected from a group consisting of i) a first substituent being one selected from a group consisting of a hydryl group, an amino group, a nitro group, a hydroxyl group and a cyan group, ii) a second substituent being one selected from a group consisting of (CH 2 ) n X, a straight (CH 2 ) n  alkyl group, a (CH 2 ) n  alkoxyl group, a branched (CH 2 ) n  alkyl group, a C 3 ˜C 12  nephthenic group, and a C 3 ˜C 12  cyclic alkoxyl group, wherein 1≦n≦12, and X is a halogen, iii) a third substituent being one selected from a group consisting of a straight C 1 ˜C 8  alkyl group with a double-bond, a C 1 ˜C 8  alkoxyl group with a double-bond, a branched C 1 ˜C 8  alkyl group with a double-bond and a C 3 ˜C 8  nephthenic group with a double-bond, and iv) a fourth substituent of a C 5 ˜C 12  heterocyclic group.

Description:
CROSS-REFERENCES TO RELATED APPLICATIONS 
       [0001]    This is a divisional application of U.S. patent application Ser. No. 12/193,564 filed on Aug. 18, 2008, which is incorporated herein by reference as if fully set forth. 
     
    
     FIELD OF THE INVENTION 
       [0002]    The present invention relates to heteroannelated anthraquinone derivatives for inhibiting a proliferation activity of a cancer cell, and more particularly to a series of heteroannelated anthraquinone derivatives and the synthesis method thereof. 
       BACKGROUND OF THE INVENTION 
       [0003]    In normal somatic cells, the telomere, which is located at the end of a chromosome, gets shortened at each time of cell mitosis. When the telomere is shortened to some level, the cell will lose the ability of replication and go into apoptosis stage. Telomerase, which is a ribonucleoprotein, acts on the telomere in a eukaryocyte, so as to prolong or maintain the length of the telomere. A telomerase mainly includes two portions; one is a protein sub-unit with activity of reverse transcription, i.e. the human telomerase reverse transcriptase (hTERT), and the other one is an RNA template for synthesizing repeated sequences of the telomerase, i.e. the human telomerase RNA component (hTR), wherein the RNA template includes the single RNA sequence, -AAUCCC, which is complementary to the telomerase sequence. Telomerase activity is rarely detected in normal human somatic cells, but is usually detected in the cells that keep proliferating, such as hematopoietic cells, embryogenic cells, stem cells, etc. It is estimated that about 85-90% of human tumor cells have telomerase activity, and that is the reason why tumor cells do not go into apoptosis like a normal cell and can keep proliferating (Urquidi et al.,  Annu. Rev. Med.  2000, 51, 65-79). Reductions in hTERT mRNA expression level and telomerase activity are observed during the processes of cell going aged or immortalized (Bestilny et al.,  Cancer Res.  1996, 56, 3796-802). Furthermore, the telomerase activity of a somatic cell that should not express the telomerase activity could be reproduced by introduction of the hTERT cDNA thereinto for a high level expression of telomerase activity (Bodnar et al.,  Science.  1998, 279, 349-52). 
         [0004]    The telomere at chromosome ends of eukaryotic cells is guanine-rich. In normal physiological conditions, the single strand DNA of the telomere spontaneously forms a G-quadruplex structure. The G-quadruplex structure includes two portions, wherein one is a small loop composed of TTA, and the other one is a guanine-tetrad composed of four guanines formed by cyclic hydrogen bonds. In order to inhibit the differentiation of tumor cells, an alternative besides the direct inhibition to telomerase activity is to stabilize the G-quadruplex structure for inhibiting its reaction with the complementary single strand RNA (AAUCCC), so as to prevent the telomerase from extending the telomere. Chromosome replications of tumor cells may be inhibited by the mentioned method, so as to achieve the anti-cancer effect directly or indirectly (Smogorzewska et al.,  Annu. Rev. Biochem.  2004, 73, 177-208). 
         [0005]    It is observed in current studies that anthraquinone can stabilize the G-quadruplex structure for its formula with plane tri-cyclic structure. According to the researches to the quinoline derivatives (10H-indolo[3,2-b]quinoline) with tetra-cyclic structure, berberin with non-plane polycyclic structure and the analogs synthesized therefrom, it is known that the aromatic groups of the mentioned compounds play an important role in the bonding to the G-quardruplex structure. Over-expressions of known oncogenes usually induce cancers and are associated with many cell proliferation disorders, such as chronic lymphocytic leukemia, esophagus cancer, myeloma, etc. In additions, those genes also participate in many pathological and physiological processes. Many experiments have proved that over-expressions of tumor suppressor genes play important role in the prevention and treatment of tumors. Therefore, the research and development of the drugs for curing cell proliferation disorders can be applied in the cure of human cancers, just like the disclosures of Canadian Patent No. 2,428,206. 
         [0006]    Although it has been published that a heteroannelated anthraquinone derivative can be synthesized by an acylation reaction of 1,2-diaminoanthraquinone to obtain a bis-substituent derivative, followed by a consensation reaction. However, this method only discloses the substituent of aromatic groups, and has a poor production rate (Peng et al.,  J. Org. Chem.  2005, 70, 10524-31). 
         [0007]    Based on the above, the present invention provides heteroannelated anthraquinone derivatives and the synthesis method thereof, which is accomplished by preserving the chromophore group with plane tri-cyclic structure and the carbonyl groups at 9 and 10, which have better binding ability, then changing the tri-cyclic structure into tetra-cyclic structure and adding various side chains derived from different modified substituents, so as to synthesize a series of heteroannelated anthraquinone derivatives. 
       SUMMARY OF THE INVENTION 
       [0008]    The present invention provides a series of heteroannelated anthraquinone derivatives for inhibiting the proliferation activity of cancer cells, which facilitate the study and application regarding cancer cells. 
         [0009]    In accordance with the first aspect of the present invention, a heteroannelated anthraquinone derivative compound is provided. The compound is represented by a formula (I): 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1  is a substituent being one selected from a group consisting of i) a first substituent being one selected from a group consisting of a hydryl group, an amino group, a nitro group, a hydroxyl group and a cyan group, ii) a second substituent being one selected from a group consisting of (CH 2 ) n X, a straight (CH 2 ) n  alkyl group, a (CH 2 ) n  alkoxyl group, a branched (CH 2 ) n  alkyl group, a C 3 ˜C 12  nephthenic group, and a C 3 ˜C 12  cyclic alkoxyl group, wherein 1≦n≦12, and X is a halogen, iii) a third substituent being one selected from a group consisting of a straight C 1 ˜C 8  alkyl group with a double-bond, a C 1 ˜C 8  alkoxyl group with a double-bond, a branched C 1 ˜C 8  alkyl group with a double-bond and a C 3 ˜C 8  nephthenic group with a double-bond, and iv) a fourth substituent of a C 5 ˜C 12  heterocyclic group, wherein one of the nephthenic group and the heterocyclic group further has at least one of an ortho-substitution, a meta-substitution and a para-substitution, and comprises at least a fifth substituent for any of the substitutions being one selected from a group consisting of an alkyl group with a C 1 ˜C 3  substituent branch, an amino group, a nitro group, a hydroxyl group and a cyan group, a C 1 ˜C 5  alkyl group, a halogen substituted C 1 ˜C 5  alkyl group, a C 1 ˜C 5  alkoxyl group, a halogen substituted C 1 ˜C 5  alkoxyl group, a C 1 ˜C 5  cyclic alkoxyl group, and a halogen substituted C 1 ˜C 5  cyclic alkoxyl group. 
         [0010]    Preferably, the halogen is one selected from a group consisting of a fluorine, a chlorine, a bromine and an iodine. 
         [0011]    Preferably, the second substituent is one selected from a group consisting of a methyl group, an ethyl group, a propyl group, a butyl group, an isobutyl group, a pentyl group, an isopentyl group, a cyclopentyl group, a heptyl group, an isoheptyl group, a cycloheptyl group, an octyl group, an isooctyl group, a cyclooctyl group, a straight alkyl group with a branch substituted by a straight C 1 ˜C 5  alkyl group, a nephthenic group with a branch substituted by a straight C 1 ˜C 5  alkyl group, alkoxyl derivatives of the mentioned alkyl groups, and halogenated derivatives of the mentioned alkyl groups. 
         [0012]    Preferably, the third substituent is one selected from a group consisting of a vinyl group, a propenyl group, a butenyl group, an isobutenyl group, a pentenyl group, an isopentenyl group, a cyclopentenyl group, a hexenyl group, a cyclohexenyl group, a heptenyl group, an cycloheptenyl group, a straight alkyl group with a branch substituted by a straight C 1 ˜C 3  alkyl group, a nephthenic group with a branch substituted by a straight C 1 ˜C 3  alkyl group, alkoxyl derivatives of the mentioned groups, and halogenated derivatives of the mentioned groups. 
         [0013]    Preferably, the heteroannelated anthraquinone derivative compound is used as an effective component together with an excipient to provide a pharmaceutic composition for inhibiting one selected from a group consisting of a growth of a cancer cell, a disease of cell proliferation, and a growth of cell telomere. 
         [0014]    In accordance with the second aspect of the present invention, a heteroannelated anthraquinone derivative compound is provided. The compound is represented by a formula (II): 
         [0000]    
       
                 
         
             
             
         
       
     
         [0015]    Preferably, the heteroannelated anthraquinone derivative compound is used as an effective component together with an excipient to provide a pharmaceutic composition for inhibiting one selected from a group consisting of a growth of a cancer cell, a disease of cell proliferation, and a growth of cell telomere. 
         [0016]    In accordance with the third aspect of the present invention, a heteroannelated anthraquinone derivative compound is provided. The compound is represented by a formula (III): 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein either one of R 2  and R 3  is one of i) a first substituent being one of a hydryl group and a sulfuryl-group, and ii) a second substituent being one selected from a group consisting of a C 1 ˜C 8  alkyl group, a C 1 ˜C 8  alkoxyl group, a C 3 ˜C 8  nephthenic group, and a C 3 ˜C 8  cyclic alkoxyl group, a straight alkyl group with a branch substitutent, a nephthenic group with a branch substitutent by a straight C 1 ˜C 5  alkyl group and halogenated derivatives of the mentioned substituent groups. 
         [0017]    Preferably, the second substituent is one selected from a group consisting of a methyl group, an ethyl group, a propyl group, a butyl group, an isobutyl group, a pentyl group, an isopentyl group, a cyclopentyl group, a heptyl group, an isoheptyl group, a cycloheptyl group, an octyl group, an isooctyl group, a cyclooctyl group, a phenyl group, a benzyl group, a phenethyl group, a straight alkyl group with a branch substituted by a straight C 1 ˜C 3  alkyl group, a nephthenic group with a branch substituted by a straight C 1 ˜C 3  alkyl group, alkoxyl derivatives of the mentioned substituent groups, and halogenated derivatives of the mentioned substituent groups. 
         [0018]    Preferably, the heteroannelated anthraquinone derivative is used as an effective component together with an excipient to provide a pharmaceutic composition for inhibiting one selected from a group consisting of a growth of a cancer cell, a disease of cell proliferation, and a growth of cell telomere. 
         [0019]    In accordance with the fourth aspect of the present invention, a heteroannelated anthraquinone derivative compound is provided. The compound is represented by a formula (IV): 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 4  is one selected from a group consisting of a hydryl group, a C 1 ˜C 4  alkyl group, a C 1 ˜C 4  alkoxyl group, a C 1 ˜C 4  ketone group, a straight alkyl group with a branch substituted by a straight C 1 ˜C 3  alkyl group, a halogen substituted C 1 ˜C 4  alkyl group, and a C 1 ˜C 4  alkoxyl group.
 
Preferably, A compound as claimed in claim  12 , being used as an effective component together with an excipient to provide a pharmaceutic composition for inhibiting one selected from a group consisting of a growth of a cancer cell, a disease of cell proliferation, and a growth of cell telomere.
 
         [0020]    In accordance with the fifth aspect of the present invention, a method for manufacturing a compound having the formula (I) is provided. The method includes steps of a) dissolving a diaminoanthraquinone in a dimethylformamide solution for forming a solution A, b) adding and dissolving a chloroacetyl chloride in the solution A for forming a solution B, c) mixing and reacting the solution B by a reverse flow method, and then transferring the solution B into an icy water for forming a solution C, d) filtering the solution C for obtaining a precipitate, and e) washing the precipitate by using an ethanol for obtaining the compound of the formula (I). 
         [0021]    In accordance with the sixth aspect of the present invention, a method for manufacturing a compound having the formula (I) is provided. The method includes steps of a) dissolving a diaminoanthraquinone in a dimethylformamide solution for forming a solution A, b) adding and dissolving a reagent in the solution A for forming a solution B, wherein the reagent is one of a benzaldehyde and a carbon disulfide, c) catalyzing a reaction of the solution B by adding a concentrated sulfuric acid thereinto, and then transferring the solution B into an ice water for forming a solution C, d) filtering the solution C for obtaining a precipitate, and e) washing the precipitate by using an ethanol for obtaining the compound of the formula (I), wherein when the reagent is the carbon disulfide, a triethylamine is further added into the solution B before the step c). 
         [0022]    In accordance with the seventh aspect of the present invention, a method for manufacturing a compound having the formula (III) is provided. The method includes steps of a) dissolving a diaminoanthraquinone in an acetone for forming a solution A, b) adding a concentrated sulfuric acid into the solution A for forming a solution B, c) transferring the solution B into a potassium carbonate column for obtaining a solution C, and d) using a methanol to crystallize the compound of the formula (III) in the solution C. 
         [0023]    Preferably, the step b) is performed in a room temperature. 
         [0024]    In accordance with the eighth aspect of the present invention, a method for manufacturing a compound having the formula (IV) is provided. The method includes steps of a) dissolving a diaminoanthraquinone in a dimethylformamide solution for forming a solution A, b) adding a glyoxal ethanol solution into the solution A for forming a solution B, c) reacting the solution B by a reverse flow reaction, d) filtering the solution B for obtaining a precipitate, and e) washing the precipitate by using a hot alcohol and a dichloromethane for separating out the compound of the formula (IV). 
         [0025]    Alternatively, in some steps of the above-mentioned methods, the production rate will increase if the solvents used for dissolving the diaminoanthraquinone contain less water. In the purification steps for the products, alcohol could be used for crystallization; alternatively, hot alcohol could be used for washing the products. The products with high solubility could be dissolved in alcohol before crystallization. The products with low solubility need to be washed by hot alcohol to wash out initial material or impurities and by-products generated in the reaction. Compared with recrystallization, although parts of products would be lost in the washing steps, it would be easier to obtain the purified products. 
         [0026]    The compound provided in the present invention could be supplied with excipients, carriers or diluent, such starch or binder like carboxymethyl cellulose (CMC), so as to prepare granulated pill, tablet, or capsule. Alternatively, the compound could be dissolved in phosphate buffer for adjusting the pH thereof, so as to prepare injection. The compound could be supplied with penetration enhancer, so as to prepare absorbate by skin. 
         [0027]    Additional objects and advantages of the invention will be set forth in the following descriptions. 
     
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT 
       [0028]    The present invention will now be described more specifically with the experiment results of the following embodiments. It is to be noted that the following descriptions of preferred embodiments of this invention are presented herein for the purposes of illustration and description only; it is not intended to be exhaustive or to be limited to the precise form disclosed. 
         [0029]    Concretely speaking, the method for manufacturing the heteroannelated anthraquinone derivative includes cyclization and condensation reactions. 
       Embodiment 1 
     2-Methyl-1(3)H-anthra[1,2-d]imidazole-6,11-dione, No. 2 
       [0030]    1,2-Diaminoanthraquinone (1.19 g, 5 mmol) is dissolved in 30 mL of N,N-dimethylformamide, and chloroacetyl chloride (0.5 mL, 6 mmol) is added thereinto. After ten hours of mixing and reacting by a reverse flow, the mixture is transferred into 200 mL of icy water. After filtering, the precipitate is collected and washed by hot alcohol, so as to obtain the black compound No. 2. 
         [0031]    The compound No. 2 has the following characterstics: MW 262.0724 (C 16 H 9 N 2 O 2 ); R f : 0.79 (ethyl acetate:dichloromethane=1:4); IR (KBr) cm −1 : 1667 (CO); EI-MS m/z: 262 (M + , 100%);  1 H-NMR (300 MHz, DMSO-d 6 ) δ (ppm): 2.72 (3H, s, —CH 3 ), 7.75-7.82 (2H, m, Ar—H 7,10 ), 7.93 (1H, d, J=8.4 Hz, Ar—H 5 ), 8.13 (1H, d, J=8.4 Hz, Ar—H 4 ), 8.19-8.23 (1H, m, Ar—H 8,9 ), 11.01 (1H, br, —NH); and  13 C-NMR (75 MHz, DMSO-d 6 ) δ (ppm): 23.89, 120.23, 121.22, 125.29, 126.19, 126.75, 127.19, 128.17, 128.87, 132.98, 134.18, 134.42, 148.22, 158.09, 182.43 ( C O), 185.13 ( C O). 
       Embodiment 2 
     2-Chloroacetyl-1(3)H-anthra[1,2-c]imidazole-6,11-dione, No. 3 
       [0032]    
       
                 
         
             
             
         
       
     
         [0033]    Except controlling the reacting temperature in 50-60° C., all steps are identical with the steps for manufacturing the compound No. 2, and the yellowish brown compound No. 3 can be obtained. 
         [0034]    The compound No. 3 has the following characterstics: MW 296.0353 (C 16 H 9 N 2 O 2 Cl); R f : 0.5 (ethyl acetate:dichloromethane=1:4); IR (KBr) cm −1 : 3359 (NH), 1660 (CO); HRMS (ESI-TOF) m/z: calcd for C 16 H 10 N 2 O 2 Cl +  [M+H] + : 297.0425, found: 297.0426;  1 H-NMR (300 MHz, CDCl 3 ) δ (ppm): 4.92 (2H, s, —CH 2 Cl), 7.80-7.83 (2H, m, Ar—H 7,10 ), 8.08 (1H, d, J=8.4 Hz, Ar—H 5 ), 8.24 (1H, d, J=8.4 Hz, Ar—H 4 ), δ8.26-8.35 (2H, m, Ar—H 8,9 ), δ11.21 (1H, br, —NH); and  13 C-NMR (75 MHz, DMSO) δ (ppm): 37.80, 119.35, 121.27, 125.95, 126.83, 127.40, 129.06, 132.35, 133.47, 133.64, 134.88, 135.10, 148.89, 156.93, 183.04 (CO), 183.83 (CO). 
       Embodiment 3 
     2-Ethyl-1(3)H-anthra[1,2-d]imidazole-6,11-dione, No. 4 
       [0035]    
       
                 
         
             
             
         
       
     
         [0036]    1,2-Diaminoanthraquinone (1.19 g, 5 mmol) was dissolved in dimethylformamide (30 mL), and propionaldehyde (0.29 g, 5 mmol) is added thereinto. Concentrated sulfuric acid (0.1 mL) is added thereinto for catalyzation. After mixing and reacting at room temperature for one hour, the reacted mixture is transferred into 200 mL of icy water and is extracted by using dichloromethane. The extract is dried, and crystallized by using alcohol, so as to obtain the brown compound No. 4. 
         [0037]    The compound No. 4 has the following characterstics: MW 276.0899 (C 17 H 12 N 2 O 2 ); R f : 0.75 (ethyl acetate:dichloromethane=1:4); IR (KBr) cm −1 : 1669 (CO); HRMS (ESI-TOF) m/z: calcd for C 17 H 13 N 2 O 2   +  [M+H] + : 277.0971, found: 277.0975 calcd for C 17 H 12 N 2 O 2 Na +  [M+Na] + : 299.0971, found: 299.0794;  1 H-NMR (300 MHz, CDCl 3 ) δ (ppm): 1.51 (3H, t, J=7.5 Hz, —CH 3 ), 3.05 (2H, q, J=7.5 Hz, —CH 2 —), 7.73-7.81 (2H, m, Ar—H 7,10 ), 7.99 (1H, d, J=8.4 Hz, Ar—H 5 ), δ8.16 (1H, d, J=8.4 Hz, Ar—H 4 ), δ8.21-8.23 (1H, m, Ar—H 9 ), δ8.27-8.31 (1H, m, Ar—H 8 ), δ10.85 (1H, br, —NH); and  13 C-NMR (75 MHz, CDCl 3 ) δ (ppm): 11.87, 22.89, 117.74, 121.50, 125.21, 126.47, 127.55, 128.21, 132.72, 133.24, 133.72, 133.99, 134.37, 148.90, 161.64, 182.81 ( C O), 185.15 ( C O). 
       Embodiment 4 
     2-Isopropyl-1(3)H-anthra[1,2-c]imidazole-6,11-dione, No. 5 
       [0038]    
       
                 
         
             
             
         
       
     
         [0039]    All steps for manufacturing the yellow compound No. 5 are identical with the steps of Embodiment 3, except that propionaldehyde is substituted by isobutyraldehyde (0.41 g, 5 mmol). 
         [0040]    The compound No. 5 has the following characterstics: MW 290.1055 (C 18 H 14 N 2 O 2 ); R f : 0.7 (ethyl acetate:dichloromethane=1:4); IR (KBr) cm −1 : 3445 (NH), 1662 (CO); HRMS (ESI-TOF) m/z: calcd for C 18 H 15 N 2 O 2   +  [M+H] + : 291.1120, found: 291.1123;  1 H-NMR (300 MHz, CDCl 3 ) δ (ppm): δ1.56 (6H, d, J=6.6 Hz, —CH 3 ), δ3.40 (1H, sp, J=6.6 Hz, —CH—), δ7.78-7.85 (2H, m, Ar—H 7,10 ), δ8.11 (1H, d, J=8.4 Hz, Ar—H 5 ), δ8.23 (1H, d, J=8.4 Hz, Ar—H 4 ), δ8.25-8.36 (2H, m, Ar—H 8,9 ), δ10.88 (1H, s, —NH); and  13 C-NMR (75 MHz, CDCl 3 ) δ (ppm): 21.15, 29.21, 117.66, 121.36, 125.21, 126.32, 127.42, 128.05, 132.49, 133.10, 133.61, 133.86, 134.24, 148.71, 165.35, 181.05 (C O ), 182.73 (C O ). 
       Embodiment 5 
     2-Butyl-1(3)H-anthra[1,2-d]imidazole-6,11-dione, No. 6 
       [0041]    
       
                 
         
             
             
         
       
     
         [0042]    All steps for manufacturing the brown compound No. 6 are identical with the steps of Embodiment 3, except that propionaldehyde is substituted by pentanal (0.45 g, 5 mmol). 
         [0043]    The compound No. 6 has the following characterstics: MW 304.1212 (C 19 H 16 N 2 O 2 ); R f : 0.65 (ethyl acetate:dichloromethane=1:4); IR (KBr) cm −1 : 1669 (CO); HRMS (ESI-TOF) m/z: calcd for C 19 H 17 N 2 O 2   +  [M+H] + : 305.1276, found: 305.1282 calcd for C 19 H 15 N 2 O 2   − [M−H]   − : 303.1131, found: 303.1135;  1 H-NMR (300 MHz, CDCl 3 ) δ (ppm): δ1.00 (3H, t, J=7.2 Hz, —CH 3 ), δ1.50 (2H, sx, J=7.5 Hz, —CH 2 —), δ1.93 (2H, qt, J=7.8 Hz, —CH 2 —), δ3.04 (2H, t, J=7.5 Hz, —CH 2 —), δ7.62-7.83 (2H, m, Ar—H 7,10 ), δ8.03 (1H, d, J=8.4 Hz, Ar—H 5 ), δ8.20, 1H, d, J=8.1 Hz, Ar—H 4 ), δ8.24-8.35 (2H, m, Ar—H 8,9 ), δ10.83 (1H, s, —NH); and  13 C-NMR (75 MHz, CDCl 3 ) δ (ppm): 12.98, 21.78, 28.60, 29.27, 117.32, 121.07, 124.64, 125.98, 127.08, 127.83, 132.17, 132.84, 133.20, 133.61, 133.86, 148.25, 160.29, 182.31 (C O ), 184.78 (C O ). 
       Embodiment 6 
     2-sec-Butyl-1(3)H-anthra[1,2-d]imidazole-6,11-dione, No. 7 
       [0044]    
       
                 
         
             
             
         
       
     
         [0045]    All steps for manufacturing the yellow compound No. 7 are identical with the steps of Embodiment 3, except that propionaldehyde is substituted by methylbutyraldehyde (0.46 g, 5 mmol). 
         [0046]    The compound No. 7 has the following characterstics: MW 304.1212 (C 19 H 16 N 2 O 2 ); R f : 0.57 (ethyl acetate:dichloromethane=1:4); IR (KBr) cm −1 : 1665 (CO); HRMS (ESI-TOF) m/z: calcd for C 19 H 17 N 2 O 2   +  [M+H] + : 305.1276, found: 305.1280 calcd for C 19 H 15 N 2 O 2   −  [M−H]: 303.1131, found: 303.1137;  1 H-NMR (300 MHz, CDCl 3 ) δ (ppm): δ1.00 (3H, t, J=7.2 Hz, —CH 3 ), δ1.52 (3H, d, J=6.9 Hz, —CH 3 ), δ1.82-2.02 (2H, m, —CH 2 —), δ3.04 (1H, sx, J=7.2 Hz, —CH—), δ7.62-7.83 (2H, m, Ar—H 7,10 ), δ8.03 (1H, d, J=8.4 Hz, Ar—H 5 ), δ8.20 (1H, d, J=8.1 Hz, Ar—H 4 ), δ8.24-8.35 (2H, m, Ar—H 8,9 ), δ10.83 (1H, s, —NH); and  13 C-NMR (75 MHz, CDCl 3 ) δ (ppm): 11.09, 18.09, 28.40, 35.71, 117.39, 121.07, 124.75, 125.95, 127.09, 127.84, 131.92, 132.83, 133.22, 133.59, 133.87, 148.06, 164.30, 182.31 (C O ), 184.82 (C O ). 
       Embodiment 7 
     2-tert-Butyl-1(3)H-anthra[1,2-c]imidazole-6,11-dione, No. 8 
       [0047]    
       
                 
         
             
             
         
       
     
         [0048]    All steps for manufacturing the yellow compound No. 8 are identical with the steps of Embodiment 3, except that propionaldehyde is substituted by trimethylacetaldehyde (0.46 g, 5 mmol). 
         [0049]    The compound No. 8 has the following characterstics: MW 304.1212 (C 19 H 16 N 2 O 2 ); R f : 0.8 (ethyl acetate:dichloromethane=1:4); IR (KBr) 3568 (NH), 1664 (CO); HRMS (ESI-TOF) m/z: calcd for C 19 H 17 N 2 O 2   +  [M+H] + : 305.1276, found: 305.1283 calcd for C 19 H 15 N 2 O 2   −  [M−H] − : 303.1131, found: 303.1136;  1 H-NMR (300 MHz, CDCl 3 ) δ (ppm): δ1.58 (9H, s, —C(CH 3 ) 3 ), δ7.77-7.84 (2H, m, Ar—H 7,10 ), δ8.08 (1H, d, J=8.4 Hz, Ar—H 5 ), δ8.21 (1H, d, J=8.4 Hz, Ar—H 4 ), δ8.25-8.28 (1H, m, Ar—H 8 ), δ8.33-8.36 (1H, m, Ar—H 9 ), δ10.83 (1H, s, —NH); and  13 C-NMR (75 MHz, CDCl 3 ) δ (ppm): 29.24, 117.79, 121.47, 125.41, 126.39, 127.56, 128.17, 132.70, 133.23, 133.74, 133.96, 134.37, 148.73, 168.00, 182.77 (C O ), 185.26 (C O ). 
       Embodiment 8 
     2-Heptyl-1(3)H-anthra[1,2-c]imidazole-6,11-dione, No. 9 
       [0050]    
       
                 
         
             
             
         
       
     
         [0051]    All steps for manufacturing the brown compound No. 9 are identical with the steps of Embodiment 3, except that propionaldehyde is substituted by octanal (0.29 g, 5 mmol). 
         [0052]    The compound No. 9 has the following characterstics: MW 346.1681 (C 22 H 22 N 2 O 2 ); R f : 0.85 (ethyl acetate:dichloromethane=1:4); IR (KBr) 3447 (NH), 1664 (CO); HRMS (ESI-TOF) m/z: calcd for C 22 H 23 N 2 O 2   +  [M+H] + : 347.1754, found: 347.1752;  1 H-NMR (300 MHz, CDCl 3 ) δ(ppm): δ0.87-0.91 (3H, m, —CH 3 ), δ1.26-1.35 (6H, m, δ1.56 (2H, sx, J=7.0 Hz, —CH 2 —), δ2.36 (2H, q, J=7.0 Hz, —CH 2 —), δ2.71 (2H, t, J=7.0 Hz, —CH 2 —), δ7.75-7.81 (2H, m, Ar—H 7,10 ), δ8.04 (1H, d, J=8.0 Hz, Ar—H 5 ), δ8.17 (1H, d, J=8.0 Hz, Ar—H 4 ), δ8.23-8.25 (1H, m, Ar—H 8 ), δ8.31-8.33 (1H, m, Ar—H 9 ), δ10.93 (1H, s, —NH); and  13 C-NMR (75 MHz, CDCl 3 ) δ (ppm): 14.08, 22.63, 27.99, 28.79, 29.24, 29.46, 31.79, 117.49, 121.66, 125.28, 126.37, 127.54, 130.56, 133.27, 133.67, 134.06, 134.31, 137.37, 149.40, 158.89, 182.69 (C O ), 185.25 (C O ). 
       Embodiment 9 
     (E)-2-(But-1-enyl)-1(3)H-anthra[1,2-c]imidazole-6,11-dione, No. 10 
       [0053]    
       
                 
         
             
             
         
       
     
         [0054]    All steps for manufacturing the brown compound No. 10 are identical with the steps of Embodiment 3, except that propionaldehyde is substituted by trans-2-pentenal (0.46 g, 5 mmol). 
         [0055]    The compound No. 10 has the following characterstics: MW 302.1055 (C 19 H 15 N 2 O 2 ); R f : 0.57 (ethyl acetate:dichloromethane=1:4); IR (KBr) cm −1 : 1664 (CO); EI-MS m/z: 302 (M + , 100%);  1 H-NMR (300 MHz, CDCl 3 ) δ (ppm): δ0.98 (3H, t, J=6.9 Hz, —CH 3 ), δ1.94-1.98 (2H, m δ6.16-6.29 (1H, m, —CH—), δ6.51 (1H, d, J=18 Hz, —CH—), δ7.68 (1H, d, J=8.4 Hz, Ar—H 5 ), δ7.82-7.89 (2H, m, Ar—H 7,10 ), δ8.14 (1H, d, J=8.1 Hz, Ar—H 4 ), δ8.27-8.35 (2H, m, Ar—H 8,9 ), δ10.74 (1H, s, —NH); and  13 C-NMR (75 MHz, CDCl 3 ) δ (ppm): 14.39, 27.40, 117.37, 120.03, 121.07, 124.75, 125.95, 127.09, 127.84, 131.92, 132.83, 133.22, 133.59, 133.87, 134.90, 135.37, 149.06, 182.73 (C O ), 185.18 (C O ). 
       Embodiment 10 
     2-Mercapto-1(3)H-anthra[1,2-d]imidazole-6,11-dione, No. 23 
       [0056]    
       
                 
         
             
             
         
       
     
         [0057]    1,2-Diaminoanthraquinone (1.19 g, 5 mmol) is dissolved in N,N-dimethylformamide (30 mL), and triethylamine (3 mL) is further added thereinto after carbon disulfide (0.4 g, 5 mmol) is added thereinto. After mixing in room temperature and performing reverse flow for ten hours, the reacted mixture is transferred into 200 mL of icy water. After filtering, the precipitate is collected and washed by hot alcohol, so as to obtain reddle compound No. 23 with melting point of 407-409° C., and the production rate is 80%. 
         [0058]    The compound No. 23 has the following characterstics: MW 280.0306 (C 15 H 8 N 2 O 2 S); R f : 0.80 (ethyl acetate:dichloromethane=1:4); IR (KBr) 3221 (NH), 3192 (NH), 1665 (CO); HRMS (ESI-TOF) m/z: calcd for C 15 H 9 N 2 O 2 S +  [M+H] + : 281.0379, found: 281.0389;  1 H-NMR (300 MHz, DMSO-d 6 ) δ (ppm): δ7.54 (1H, d, J=8.1 Hz, Ar—H 5 ), δ8.02 (1H, d, J=8.1 Hz, Ar—H 4 ), δ7.91-7.94 (2H, m, Ar—H 7,10 ), δ8.18-8.22 (2H, m, Ar—H 8,9 ), δ12.73 (1H, s, —NH), δ13.29 (1H, s, —NH); and  13 C-NMR (75 MHz, DMSO-d 6 ) δ (ppm): 113.89, 115.27, 122.41, 126.26, 126.76, 126.88, 130.95, 132.89, 133.06, 134.25, 134.47, 138.19, 172.89, 181.79 (C O ), 182.46 (C O ). 
       Embodiment 11 
     2-Phenyl-1(3)H-anthra[1,2-d]imidazole-6,11-dione, No. 11 
       [0059]    
       
                 
         
             
             
         
       
     
         [0060]    1,2-Diaminoanthraquinone (1.19 g, 5 mmol) is dissolved in dimethylformamide (30 mL), and concentrated sulfuric acid (0.1 mL) is further added thereinto for catalyzation after benzaldehyde (0.6 mL, 5 mmol) is added thereinto. After mixing and reacting in room temperature for one hour, the reacted mixture is transferred into 200 mL of icy water. After filtering, the precipitate is collected and washed by hot alcohol, so as to obtain yellowish brown compound No. 11. 
         [0061]    The compound No. 11 has the following characterstics: MW 324.0899 (C 21 H 12 N 2 O 2 ); R f : 0.55 (ethyl acetate:dichloromethane=1:4); IR (KBr) cm −1 : 3296 (NH), 1660 (CO); EI-MS m/z: 324 (M + , 100.00%), 325 (19%); HRMS (ESI-TOF) m/z: calcd for C 21 H 13 N 2 O 2   +  [M+H] + : 325.0971, found: 325.0973;  1 H-NMR (300 MHz, DMSO-d 6 ) δ (ppm): δ 7.57 (3H, t, J=3 Hz, Ar′—H 3,4,5 ), δ7.89 (2H, m, Ar—H 7,10 ), δ8.03 (1H, d, J=8.4 Hz, Ar—H 5 ), δ8.08 (1H, d, J=8.4 Hz, Ar—H 4 ), δ8.16 (2H, m, Ar—H 8,9 ), δ8.40 (2H, dd, J=6.3 Hz, Ar′—H 2,6 ); and  13 C-NMR (75 MHz, DMSO-d 6 ) δ (ppm): 119.62, 121.72, 125.06, 126.85, 127.42, 128.79, 128.86, 129.41, 129.50, 131.72, 133.72, 133.77, 134.92, 135.07, 149.26, 158.25, 183.06 (C O ), 183.79 (C O ). 
       Embodiment 12 
     2-(4-N,N-Dimethylamino)phenyl-1(3)H-anthra[1,2-d]imidazole-6,11-dione, No. 12 
       [0062]    
       
                 
         
             
             
         
       
     
         [0063]    All steps for manufacturing the deep brown compound No. 12 are identical with the steps of Embodiment 11, except that benzaldehyde is substituted by 4-dimethylaminobenzaldehyde (0.77 g, 5 mmol). 
         [0064]    The compound No. 12 has the following characterstics: MW 367.1321 (C 23 H 17 N 3 O 2 ); R f : 0.6 (ethyl acetate:dichloromethane=1:4); IR (KBr) cm −1 : 3404 (NH), 1659 (CO); EI-MS m/z: 366 (27%), 367 (M + , 100.00%), 368 (20%); HRMS (ESI-TOF) m/z: calcd for C 23 H 18 N 3 O 2   +  [M+H] + : 368.1393, found: 368.1393;  1 H-NMR (300 MHz, CDCl 3 ) δ (ppm): δ3.09 (6H, s, —N(CH 3 ) 2 ), δ6.81 (2H, d, Ar—H), δ7.79-7.82 (3H, m, Ar—H), δ8.03-8.22 (3H, m, Ar—H), δ8.27-8.36 (2H, m, Ar—H), δ11.10 (1H, br, —NH); and  13 C-NMR (75 MHz, CDCl 3 ) δ (ppm): 39.95, 111.65, 115.23, 117.13, 121.83, 124.24, 126.33, 127.37, 127.44, 128.27, 133.27, 133.45, 133.54, 134.12, 150.11, 152.10, 157.59, 182.47 (C O ), 185.09 (C O ). 
       Embodiment 13 
     2-(4-Nitrophenyl)-1(3)H-anthra[1,2-d]imidazole-6,11-dione, No. 13 
       [0065]    
       
                 
         
             
             
         
       
     
         [0066]    All steps for manufacturing the deep brown compound No. 13 are identical with the steps of Embodiment 11, except that benzaldehyde is substituted by 4-nitrobenzaldehyde (0.78 g, 5 mmol). 
         [0067]    The compound No. 13 has the following characterstics: MW 369.0750 (C 21 H 11 N 3 O 4 ); R f : 0.6 (ethyl acetate:dichloromethane=1:4); IR (KBr) 3460 (NH), 1657 (CO), 1517, 1345 (NO 2 ); EI-MS m/z: 249 (100%), 369 (M + , 35%); HRMS (ESI-TOF) m/z: calcd for C 21 H 12 N 3 O 4   +  [M+H] + : 370.0822, found: 370.0823;  1 H-NMR (300 MHz, DMSO-d 6 ) δ (ppm): δ7.79-7.82 (3H, m, Ar—H 7,10 ), δ7.14 (1H, d, J=8.1 Hz, Ar—H 4 ), δ8.23 (1H, d, J=8.1 Hz, Ar—H 5 ), δ8.23-8.32 (2H, m, Ar—H 8,9 ), δ8.39 (2H, d, J=8.1 Hz, Ar′—H 2,6 ), δ8.58 (2H, d, J=8.1 Hz, Ar′—H 3,5 ), δ10.15 (1H, br, —NH); and  13 C-NMR (75 MHz, DMSO-d 6 ) δ (ppm): 117.81, 122.43, 123.62, 125.24, 125.88, 126.10, 127.92, 133.22, 133.36, 134.53, 143.08, 146.39, 146.77, 155.89, 172.18, 178.35, 179.40, 183.20 (C O ), 185.56 (C O ). 
       Embodiment 14 
     2-(4-Hydroxy-3-methoxyphenyl)-1H-anthra[1,2-d]imidazole-6,11-dione, No. 14 
       [0068]    
       
                 
         
             
             
         
       
     
         [0069]    1,2-Diaminoanthraquinone (1.19 g, 5 mmol) is dissolved in dimethylformamide (30 mL), and concentrated sulfuric acid (0.1 mL) is further added thereinto for catalyzation after vanillin (0.77 g, 5 mmol) is added thereinto. After mixing and reacting in room temperature for one hour, the reacted mixture is transferred into 200 mL of icy water. After filtering, the precipitate is collected and washed by hot alcohol, so as to obtain brown compound No. 14. 
         [0070]    The compound No. 14 has the following characterstics: MW 370.0954 (C 22 H 14 N 2 O 4 ); R f : 0.2 (ethyl acetate:dichloromethane=1:4); IR (KBr) 3411 (OH), 3411 (NH), 1664 (CO); EI-MS m/z: 369 (57%), 370 (M + , 100%) HRMS (ESI-TOF) m/z: calcd for C 22 H 15 N 2 O 4   +  [M+H] + : 370.1026, found: 370.1025;  1 H-NMR (300 MHz, DMSO-d 6 ) δ (ppm): δ3.91 (3H, s, —OCH 3 ), δ6.90 (1H, d, J=8.4 Hz, Ar′—H 5 ), δ7.81-7.88 (3H, m, Ar—H 7,10 , Ar′—H 2 ), δ7.92-7.96 (3H, m, Ar—H 4,5 , Ar′—H 6 ), δ7.99 (1H, s, —NH), δ8.11 (2H, td, J=Hz, Ar—H 8,9 ), δ9.78 (1H, br, —OH); and  13 C-NMR (75 MHz, DMSO-d 6 ) δ (ppm): 56.57, 112.72, 116.37, 119.21, 119.65, 122.05, 122.95, 123.88, 126.81, 127.41, 128.42, 133.50, 133.64, 134.87, 135.09, 148.48, 150.87, 158.33, 182.85 (C O ), 183.79 (CO). 
       Embodiment 15 
     2-p-Tolyl-1H-anthra[1,2-d]imidazole-6,11-dione, No. 15 
       [0071]    
       
                 
         
             
             
         
       
     
         [0072]    All steps for manufacturing the twany compound No. 15 are identical with the steps of Embodiment 14, except that vanillin is substituted by p-tolualdehyde (0.7 ml, 5 mmol). 
         [0073]    The compound No. 15 has the following characterstics: MW 338.1055 (C 22 H 14 N 2 O 4 ); R f : 0.65 (ethyl acetate:dichloromethane=1:4); IR (KBr) cm −1 : 3397 (NH), 1659 (CO); EI-MS m/z: 338 (M + , 100%), 339 (24%) HRMS (ESI-TOF) m/z: calcd for C 22 H 15 N 2 O 4   +  [M+H] + : 339.1128, found: 339.1128;  1 H-NMR (300 MHz, CDCl 3 ) δ (ppm): δ2.46 (3H, s, Ar′−CH 3 ), δ7.37 (2H, d, J=8.1 Hz, Ar′—H 3,5 ), δ7.79 (2H, t, J=3.6 Hz, Ar—H 7,10 ), δ8.03 (2H, d, J=7.8 Hz, Ar′—H 2,6 ), δ8.08 (1H, d, J=8.4 Hz, Ar—H 5 ), δ8.21 (1H, d, J=8.4 Hz, Ar—H 4 ), δ8.24-8.34 (2H, m, Ar—H 8,9 ), δ11.21 (1H, s, —NH); and  13 C-NMR (75 MHz, CDCl 3 ) δ (ppm): 21.58, 117.89, 121.96, 125.44, 125.75, 126.46, 127.00, 127.58, 128.43, 130.00, 133.20, 133.26, 133.72, 133.99, 134.38, 142.05, 149.50, 156.86, 182.60 (C O ), 185.16 (C O ). 
       Embodiment 16 
     2-(4-Bromophenyl)-1H-anthra[1,2-d]imidazole-6,11-dione, No. 16 
       [0074]    
       
                 
         
             
             
         
       
     
         [0075]    All steps for manufacturing the red brown compound No. 16 are identical with the steps of Embodiment 14, except that vanillin is substituted by 4-bromobenzaldehyde (0.93 g, 5 mmol). 
         [0076]    The compound No. 16 has the following characterstics: MW 402.0004 (C 21 H 11 N 2 O 2 Br); R f : 0.4 (ethyl acetate:dichloromethane=1:4); IR (KBr) cm −1 : 3391 (NH), 1658 (CO); EI-MS m/z 402 (M + , 100%), 404 (97%), HRMS (ESI-TOF) m/z: calcd for C 21 H 12 N 2 O 2 Br +  [M+H] + : 403.0085, found: 403.0073 calcd for C 21 H 10 N 2 O 2 Br −  [M−H] − : 400.9939, found: 400.9923;  1 H-NMR (300 MHz, CDCl 3 ) δ (ppm): δ7.72 (2H, d, J=8.7 Hz, Ar′—H 3,5 ), δ7.80-7.83 (2H, m, Ar—H 7,10 ), δ8.06 (2H, d, J=8.7 Hz, Ar′—H 2,6 ), δ8.13 (1H, d, J=8.4 Hz, Ar—H 4 ), δ8.25 (1H, d, J=8.4 Hz, Ar—H 5 ), δ8.27-8.36 (2H, m, δ11.29 (1H, s, —NH); and  13 C-NMR (75 MHz, CDCl 3 ) δ (ppm): 122.18, 125.86, 126.11, 126.57, 127.64, 127.69, 128.50, 128.89, 132.61, 133.20, 133.35, 133.87, 134.01, 134.57, 149.40, 155.62, 182.63 (C O ), 185.25 (C O ). 
       Embodiment 17 
     2-(4-Cyanophenyl)-1H-anthra[1,2-d]imidazole-6,11-dione, No. 17 
       [0077]    
       
                 
         
             
             
         
       
     
         [0078]    All steps for manufacturing the yellowish brown compound No. 17 are identical with the steps of Embodiment 14, except that vanillin is substituted by 4-cyanobenzaldehyde (0.67 g, 5 mmol). 
         [0079]    The compound No. 17 has the following characterstics: MW 349.0851 (C 22 H 11 N 3 O 2 ); R f : 0.65 (ethyl acetate:dichloromethane=1:4); IR (KBr) cm −1 : 3341 (NH), 2229 (CN), 1667 (CO); HRMS (ESI-TOF) m/z: calcd for C 22 H 12 N 3 O 2 +[M+H] + : 350.0924, found: 350.0925;  1 H-NMR (300 MHz, CDCl 3 ) δ (ppm): δ7.80-7.85 (2H, m, Ar—H 7,10 ), δ8.06 (2H, d, J=8.1 Hz, Ar—H 3′,5′ ), δ8.18 (1H, d, J=8.4 Hz, Ar—H 5 ), δ8.27-8.32 (4H, m, Ar—H 4,8,2′,6′ ) δ8.35-8.38 (1H, m, Ar—H 9 ), δ11.46 (1H, s, —NH); and  13 C-NMR (75 MHz, DMSO-d 6 ) δ (ppm): 114.71, 118.04, 118.52, 122.39, 126.39, 126.63, 127.57, 127.75, 129.45, 132.76, 133.04, 133.11, 133.34, 133.93, 133.99, 134.70, 149.17, 154.25, 182.56 ( C O), 185.21 ( C O). 
       Embodiment 18 
     2-(2,5-Dimethoxyphenyl)-1H-anthra[1,2-d]imidazole-6,11-dione, No. 18 
       [0080]    
       
                 
         
             
             
         
       
     
         [0081]    All steps for manufacturing the red brown compound No. 18 are identical with the steps of Embodiment 14, except that vanillin is substituted by 2,5-dimethoxybenzaldehyde (0.89 g, 5 mmol). 
         [0082]    The compound No. 18 has the following characterstics: MW 384.1110 (C 23 H 16 N 2 O 4 ); R f : 0.4 (ethyl acetate:dichloromethane=1:4); IR (KBr) cm −1 : 3417 (NH), 1660 (C═O), 1226 (C—O); HRMS (ESI-TOF) m/z: calcd for C 23 H 17 N 2 O 4   +  [M+H] + : 385.1183, found: 385.1181;  1 H-NMR (300 MHz, CDCl 3 ) δ (ppm): δ3.93 (3H, s, Ar 2′ —OCH 3 ), δ4.21 (H, s, Ar 2 —OCH 3 ), δ7.09 (2H, d, J=1.2 Hz, Ar—H 3′,4′ ), δ7.79-7.82 (2H, m, Ar 7,10 ), δ8.13 (1H, d, J=8.1 Hz, Ar—H 5 ), δ8.13 (1H, s, Ar—H 6′ ), δ8.25 (1H, d, J=8.1 Hz, Ar—H 4 ), δ8.29-8.36 (2H, m, Ar—H 8,9 ), δ12.37 (1H, s, —NH); and  13 C-NMR (75 MHz, CDCl 3 ) δ (ppm): 56.08, 56.69, 113.13, 113.36, 116.86, 118.14, 119.98, 121.92, 124.92, 126.46, 127.54, 129.92, 132.57, 133.43, 133.70, 134.06, 134.24, 135.39, 152.20, 154.23, 155.18, 182.82 ( C O), 184.88 ( C O). 
       Embodiment 19 
     2-(Benzo[d][1,3]dioxol-5-yl)-1H-anthra[1, 2-d]imidazole-6,11-dione, No. 19 
       [0083]    
       
                 
         
             
             
         
       
     
         [0084]    All steps for manufacturing the red brown compound No. 19 are identical with the steps of Embodiment 14, except that vanillin is substituted by piperonal (0.77 g, 5 mmol). 
         [0085]    The compound No. 19 has the following characterstics: MW 368.0797 (C 22 H 12 N 2 O 4 ); R f : 0.45 (ethyl acetate:dichloromethane=1:4); IR (KBr) 3444 (NH), 1670 (C═O), 1257 (C—O), 1210 (C—O); HRMS (ESI-TOF) m/z: calcd for C 22 H 13 N 2 O 4   +  [M+H] + : 369.0867, found: 369.0887;  1 H-NMR (300 MHz, CDCl 3 ) δ (ppm) δ6.11 (2H, s, —OCH 2 O—), δ7.00 (1H, d, J=7.8 Hz, Ar—H 5′ —), δ7.67 (1H, s, Ar—H 2′ ), δ7.79-7.82 (2H, m, Ar—H 7,10 ), δ8.13 (1H, d, J=8.1 Hz, Ar—H 5 ), δ8.24 (1H, d, J=7.8 Hz, Ar—H 6′ ), δ8.25 (1H, d, J=8.1 Hz, Ar—H 4 ), δ8.29-8.36 (2H, m, Ar—H 8,9 ), δ11.18 (1H, s, —NH); and  13 C-NMR (75 MHz, CDCl 3 ) δ (ppm): 101.93, 107.37, 108.96, 117.86, 121.83, 122.05, 122.78, 125.35, 126.52, 127.62, 128.40, 133.27, 133.43, 133.76, 134.08, 134.44, 148.71, 149.62, 150.56, 156.55, 182.66 (ĈO), 185.27 ( C O). 
       Embodiment 20 
     Anthra[2,1-c][1,2,5]thiadiazole-6,11-dione, No. 22 
       [0086]    
       
                 
         
             
             
         
       
     
         [0087]    1,2-Diaminoanthraquinone (1.19 g, 5 mmol) is dissolved in THF (30 mL), and triethylamine (3 mL) is further added thereinto for catalyzation after thionyl chloride (0.15 g, 20 mmol) is dripped thereinto. After mixing and reacting in room temperature for one hour, the reacted mixture is transferred into 200 mL of icy water. After filtering, the precipitate is collected and recrystallized by hot alcohol, so as to obtain yellow compound No. 22 with melting point of 227-228° C., and the production rate is 74%. 
         [0088]    The compound No. 22 has the following characterstics: MW 266.0150 (C 14 H 6 N 2 O 2 S); R f : 0.8 (ethyl acetate:dichloromethane=1:4); IR (KBr) 1671 (CO); EI-MS m/z: 210 (57%), 238 (64%), 266 (M + , 100%), HRMS (ESI-TOF) m/z: calcd for C 14 H 7 N 2 O 2 S +  [M+H] + : 267.0223, found: 267.0226;  1 H-NMR (300 MHz, CDCl 3 ) δ (ppm): δ7.84 (1H, dd, J=12.15, 6.9 Hz, Ar—H 7 ), δ7.85 (1H, dd, J=13.2, 7.5 Hz, Ar—H 10 ), δ8.33 (1H, dd, J=22.5, 7.2 Hz, Ar—H 8 ), δ8.33 (1H, dd, J=22.5, 7.2 Hz, Ar—H 9 ), δ8.41 (1H, d, J=9.3 Hz, Ar—H 5 ), δ8.56 (1H, d, J=9.3 Hz, Ar—H 4 ); and  13 C-NMR (75 MHz, CDCl 3 )           (ppm): 125.07, 126.35, 126.99, 127.34, 127.61, 132.08, 133.47, 134.15, 134.75, 135.16, 150.93, 157.99, 181.97 ( C O), 183.31 ( C O). 
       Embodiment 21 
     2,2-Dimethyl-2,3-dihydro-1H-anthra[1,2-d]imidazole-6,11-dione, No. 20 
       [0089]    
       
                 
         
             
             
         
       
     
         [0090]    1,2-Diaminoanthraquinone (1.19 g, 5 mmol) is dissolved in dry acetone (100 mL), and concentrated sulfuric acid (0.1 mL) is further added thereinto. After mixing and reacting in room temperature for 48 hours, the reacted mixture is transferred into a potassium carbonate column. The product is collected and recrystallized by methanol, so as to obtain the purple compound 20, and the production rate is 31%. In the purification steps of the Embodiment 21, regular extraction method will reduce the production rate, and thus the basic column is used to remove the acid in the rough extract, so as to increase the production rate. 
         [0091]    The compound No. 20 has the following characterstics: Melting point: 235-237°, MW 278.1055 (C 17 H 14 N 2 O 2 ); R f : 0.5 (ethyl acetate:dichloromethane=1:4); IR (KBr) cm −1 : 3419 (NH), 3239 (NH), 1639 (CO); EI-MS m/z: 263 (100%), 278 (M + , 8.6%), HRMS (ESI-TOF) m/z: calcd for C 17 H 15 N 2 O 2   +  [M+H] + : 279.1128, found: 279.1133;  1 H-NMR (300 MHz, DMSO-d 6 ) δ (ppm): δ1.48 (6H, s, —CH 3 ), δ6.26 (1H, d, J=7.8 Hz, Ar—H 4 ), δ7.37 (1H, d, J=7.8 Hz, Ar—H 5 ), δ7.73-7.76 (m, 2H, Ar—H 7,10 ), δ8.05 (s, 1H, —NHC—), δ8.08-8.12 (m, 2H, Ar—H 8,9 ), δ8.79 (s, 1H, —CNH—); and  13 C-NMR (75 MHz, DMSO-d 6 ) δ (ppm): 30.18, 81.70, 104.02, 108.04, 120.99, 123.54, 126.32, 127.07, 133.41, 133.54, 134.79, 135.46, 143.05, 148.12, 179.89 ( C O), 182.47 ( C O). 
       Embodiment 22 
     2-Methyl-2-phenyl-2,3-dihydro-1H-anthra[1,2-d]imidazole-6,11-dione, No. 21 
       [0092]    
       
                 
         
             
             
         
       
     
         [0093]    1,2-Diaminoanthraquinone (1.19 g, 5 mmol) is dissolved in N,N-dimethylformamide (30 mL), and concentrated sulfuric acid (0.1 mL) is further added thereinto after acetophenone (0.5 ml, 6 mmol) is added thereinto. After mixing and reacting in room temperature for 72 hours, the reacted mixture is transferred into icy water (200 mL) for precipitation. The precipitate is collected and recrystallized by hot alcohol, so as to obtain the black compound 21, and the production rate is 28%. 
         [0094]    The compound No. 21 has the following characterstics: Melting point: 368-371°, MW 340.1212 (C 22 H 16 N 2 O 2 ); R f : 0.8 (ethyl acetate:dichloromethane=1:4); IR (KBr) 3348 (NH), 1671 (CO); HRMS (ESI-TOF) m/z: calcd for C 22 H 17 N 2 O 2   +  [M+H] + : 341.1284, found: 341.1033;  1 H-NMR (300 MHz, DMSO-d 6 ) δ (ppm): δ1.22 (3H, s, —CH 3 ), δ7.56-7.62 (3H, m, δ7.90-7.94 (2H, m, Ar—H 7,10 ), δ8.08 (1H, d, J=8.1 Hz, Ar—H 5 ), δ8.22 (1H, d, J=8.1 Hz, Ar—H 4 ), δ8.18-8.22 (2H, m, Ar′—H 3,5 ), δ8.40-8.42 (2H, m, Ar—H 8,9 ); and  13 C-NMR (75 MHz, DMSO) δ (ppm): 28.79, 83.56, 103.62, 109.74, 119.13, 121.35, 124.03, 126.20, 1267.76, 128.32, 128.77, 131.31, 132.99, 134.30, 134.45, 143.05, 157.25, 182.60 ( C O), 182.89 ( C O). 
       Embodiment 23 
     2,3-dimethylnaphtho[2,3-f]quinoxaline-7,12-dione, No. 24 
       [0095]    
       
                 
         
             
             
         
       
     
         [0096]    1,2-Diaminoanthraquinone (1.19 g, 5 mmol) is dissolved in N,N-dimethylformamide (30 mL), and concentrated sulfuric acid (0.1 mL) is further added thereinto after methyl vinyl ketone (0.36 g, 5 mmol) is added thereinto. After mixing and reacting in room temperature for 72 hours, the reacted mixture is transferred into icy water (200 mL) for precipitation. The precipitate is collected and recrystallized by hot alcohol, so as to obtain the black compound 24, and the production rate is 25%. 
         [0097]    The compound No. 24 has the following characterstics: Melting point&gt;400°, MW 288.0899 (C 18 H 12 N 2 O 2 ); R f : 0.6 (ethyl acetate:dichloromethane=1:4); IR (KBr) cm −1 : 1671 (CO); HRMS (ESI-TOF) m/z: calcd for C 18 H 13 N 2 O 2   +  [M+H] + : 289.0988, found: 289.0970;  1 H-NMR (300 MHz, DMSO-d 6 ) δ (ppm): δ2.72 (3H, s, —CH 3 ), δ2.88 (3H, s, —CH 3 ), δ7.91-7.94 (2H, m, Ar—H 8,11 ), δ8.07 (1H, d, J=8.4 Hz, Ar—H 5 ), δ8.16 (1H, d, J=8.4 Hz, Ar—H 4 ), δ8.19-8.21 (2H, m, Ar—H 9,10 ); and  13 C-NMR (75 MHz, DMSO-d 6 ) δ (ppm): 14.91, 30.74, 120.19, 125.46, 126.21, 126.26, 127.16, 128.18, 128.87, 133.01, 133.10, 134.19, 134.27, 134.42, 158.87, 162.28, 182.49 ( C O), 183.37 ( C O). 
       Embodiment 24 
     Naphthol-[2,3-f]quinoxaline-7,12-dione, No. 25 
       [0098]    
       
                 
         
             
             
         
       
     
         [0099]    1,2-Diaminoanthraquinone (1.19 g, 5 mmol) is dissolved in N,N-dimethylformamide (30 mL), and 40% glyoxal (0.8 g, 5 mml) in EtOH (50 mL) is added thereinto. After reverse flow for 16 hours, the water is evaporated out, and the reacted mixture is transferred into icy water (200 mL) for precipitation. The precipitate is collected and washed by hot alcohol and dichloromethane repeatedly, so as to obtain the black compound 25, and the production rate is 23%. 
         [0100]    The compound No. 25 has the following characterstics: Melting point: 270-272°, MW 260.0586 (C 16 H 8 N 2 O 2 ); R f : 0.45 (ethyl acetate:dichloromethane=1:4); IR (KBr) 3413 (NH), 3365 (NH), 1626 (CO); EI-MS m/z: 150 (54%), 238 (73%), 260 (M + , 100%); HRMS (ESI-TOF) m/z: calcd for C 16 H 9 N 2 O 2   +  [M+H] + : 261.0659, found: 261.0663;  1 H-NMR (300 MHz, CDCl 3 ) δ (ppm): δ7.82-7.87 (2H, m, Ar—H 8,11 ), δ8.29-8.36 (2H, m, Ar—H 9,10 ), δ8.48 (1H, d, J=8.7 Hz, Ar—H 5 ), δ8.72 (1H, d, J=8.7 Hz, Ar—H 6 ), δ8.99 (1H, d, J=1.5 Hz, —N═CH—), δ9.25 (1H, d, J=1.5 Hz, —CH═N—); and  13 C-NMR (75 MHz, CDCl 3 ) δ (ppm): 126.72, 127.05, 127.46, 130.05, 131.98, 133.77, 134.76, 135.18, 135.88, 135.93, 136.03, 145.42, 146.40, 147.77, 183.21 ( C O), 183.61 ( C O). 
       Embodiment 25 
     Naphtho[2,3-f]quinoxaline-2,3,7,12 (1H,4H)-tetraone, No. 26 
       [0101]    
       
                 
         
             
             
         
       
     
         [0102]    1,2-Diaminoanthraquinone (1.19 g, 5 mmol) is dissolved in N,N-dimethylformamide (30 mL), and oxalic acid (0.46 g, 5 mmol) and concentrated sulfuric acid (0.1 mL) is added thereinto. After reverse flow for 16 hours, the reacted mixture is transferred into icy water (200 mL) for precipitation. The precipitate is collected and washed by hot alcohol and, so as to obtain the black compound 26, and the production rate is 30%. 
         [0103]    The compound No. 25 has the following characterstics: Melting point: 245-246°, MW 292.0484 (C 16 H 8 N 2 O 4 ); R f : 0.25 (ethyl acetate:dichloromethane=1:4); IR (KBr) cm −1 : 1710 (CO), 1671 (CONH); EI-MS m/z: 248 (100%), 292 (M + ) HRMS (ESI-TOF) m/z: calcd for C 16 H 9 N 2 O 4   +  [M+H] + : 293.0557, found: 293.0568;  1 H-NMR (300 MHz, DMSO-d 6 ) δ (ppm): δ7.71 (1H, d, J=8.0 Hz, Ar—H 5 ), δ7.93-7.98 (2H, m, Ar—H 8,11 ), δ8.04 (1H, d, J=8.0 Hz, Ar—H 6 ), δ8.17-8.24 (2H, m, Ar—H 9,10 ), δ8.99 (1H, d, J=1.5 Hz, —NH—), δ9.25 (1H, d, J=1.5 Hz, —NH—); and  13 C-NMR (75 MHz, DMSO-d 6 ) δ (ppm); 118.08, 120.52, 122.87, 126.26, 126.34, 126.78, 127.71, 128.17, 129.58, 134.48, 134.55, 135.07, 154.64 (NHCO), 154.73 (NHCO), 180.08 ( C O), 181.07 ( C O). 
         [0104]    The chemical formula, production rates and melting points of the above-mentioned heteroannelated anthraquinone derivatives of series A are illustrated in Table 1, and the chemical formula, production rates and melting points of the above-mentioned heteroannelated anthraquinone derivatives of series B, C and D are described in the embodiments, respectively. 
         [0000]    
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 1 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Compound  
                   
                 Melting point 
                 Production 
               
               
                 No. 
                 R 1   
                 (°) 
                 Rate (%) 
               
               
                   
               
             
          
           
               
                 2 
                 —CH 3   
                 &gt;400 
                 67 
               
               
                 3 
                 —CH 2 Cl 
                 272-273 
                 86 
               
               
                 4 
                 —CH 2 CH 3   
                 193-194 
                 39 
               
               
                 5 
                 —CH(CH 3 ) 2   
                 199-200 
                 41 
               
               
                 6 
                 —(CH 2 ) 3 CH 3   
                 192-193 
                 36 
               
               
                 7 
                 —CH(CH 3 )CH 2 CH 3   
                 118-119 
                 40 
               
               
                 8 
                 —CH(CH 3 ) 3   
                 209-210 
                 37 
               
               
                 9 
                 —(CH 2 ) 6 CH 3   
                 85-87 
                 38 
               
               
                 10 
                 —CH═CHCH 2 CH 3   
                 117-119 
                 33 
               
               
                 11 
                 —C 6 H 5   
                 232-233 
                 74 
               
               
                 12 
                 —C 6 H 4 -p-N (CH 3 ) 2   
                 239-241 
                 79 
               
               
                 13 
                 —C 6 H 4 -p-NO 2   
                 342-343 
                 89 
               
               
                 14 
                 —C 6 H 3 -p-OH-m-OCH 3   
                 230-231 
                 47 
               
               
                 15 
                 —C 6 H 4 -p-CH 3   
                 256-257 
                 76 
               
               
                 16 
                 —C 6 H 4 -p-Br 
                 302-303 
                 75 
               
               
                 17 
                 —C 6 H 4 -p-CN 
                 353-354 
                 77 
               
               
                 18 
                 —C 6 H 3 -o,m-(OCH 3 ) 2   
                 251-252 
                 74 
               
               
                 19 
                 3,4-benzdioxole 
                 300-301 
                 81 
               
               
                   
               
             
          
         
       
     
         [0105]    Telomeric repeat amplification protocol (TRAP) is employed to detect the effect of the heteroannelated anthraquinone derivatives synthesized in the present invention for inhibiting the telomerase activity. In the first stage of this method, the telemerase is used to prolong the oligonucleotide with telomere sequence in the conditions of 90° C. for 10 minutes, 72° C. for 3 minutes, 50° C. for 60 seconds and 94° C. for 30 seconds (TSG4 primer: 5′-GGG ATT GGG ATT GGG ATT GGG TT-3′) In the second stage, different compounds are added into the telomerase reacted product to further replicate the telomere product by PCR (CX primer: 5′-CCCTTA CCCTTA CCCTTA CCCTAA-3′). When the compound inhibits the telomerase activity, the replication reaction can not be resumed. The PCR conditions includes 39 cycles of PCR reaction in 50° C. for 30 seconds, 72° C. for 60 seconds for 39 PCR cycles, followed by one cycle of reaction in 94° C. for 30 seconds, 50° C. for 30 seconds, 72° C. for 30 seconds and 72° C. for 1 minute, and the reaction is ended in 4° C. The PCR product is analyzed by electrophoresis using 10% acrylamide gel. In the electrophoresis results, the positive control (P) is sterile water (dddH 2 O), and the negative control (N) is 5 μl 0.1 mg/mL RNase A (CLONTECH). The positive control (P) produces lots of telomere fragment, while the negative control (N) does not. The compounds provided by the present invention inhibit the telomerase activity by stabilizing G-quadruplex structures and blocking the interaction between telomerase and telomere, or directly inhibit the telomerase activity, so as to inhibit the prolongation of telomere. It is found in the present experiments that the Embodiments A4 and A5 have better inhibition effects. 
         [0106]    In addition, it is found in the in vitro experiments performed by the development therapeutics program of US cancer research center that the heteroannelated anthraquinone derivatives synthesized in the present invention have various inhibition effects on different cancer cell lines at 1.0×10 −5  molal concentration (M) as shown in Table 2. For example, the Embodiment A2 of the present invention inhibits the growth of breast cancer cell HS578T, and the Embodiment B1 has overall and the most obvious inhibition on different cancer cells. Therefore, the heteroannelated anthraquinone derivatives synthesized in the present invention are potential drugs for inhibiting cancer cells. 
         [0000]    
       
         
               
               
               
               
               
               
             
               
               
               
               
               
               
             
           
               
                   
                 TABLE 2 
               
               
                   
                   
               
               
                   
                 No. 22 
                 No. 4 
                 No. 20 
                 No. 25 
                 No. 26 
               
               
                   
                   
               
             
             
               
                   
               
             
          
           
               
                 Non-small cell lung 
                   
                   
                   
                   
                   
               
               
                 cancer cell 
               
               
                 HOP-62 
                 −100.00 
                 97.73 
                 XXX 
                 XXX 
                 XXX 
               
               
                 HOP-92 
                 XXX 
                 41.43 
                 5.10 
                 XXX 
                 −15.08 
               
               
                 Colorectal cancer cell 
               
               
                 HCC-2998 
                 −50.00 
                 67.67 
                 136.96 
                 −7.15 
                 77.59 
               
               
                 Breast cancer cell 
               
               
                 HS 578T 
                 −7.40 
                 −18.58 
                 XXX 
                 XXX 
                 XXX 
               
               
                 MCF7 
                 −50.74 
                 69.82 
                 83.58 
                 39.68 
                 85.17 
               
               
                 MDA-MB-435 
                 −87.88 
                 84.39 
                 124.56 
                 102.03 
                 144.42 
               
               
                 MDA-MB-468 
                 −73.17 
                 XXX 
                 77.25 
                 75.28 
                 38.35 
               
               
                 T-47D 
                 −45.52 
                 63.05 
                 82.96 
                 85.19 
                 87.10 
               
               
                 Ovary cancer cell 
               
               
                 IGROV1 
                 −88.34 
                 XXX 
                 −2.80 
                 3.44 
                 13.36 
               
               
                 OVCAR-4 
                 −94.43 
                 48.81 
                 80.14 
                 94.22 
                 103.31 
               
               
                 Blood cancer cell 
               
               
                 MOLT-4 
                 −40.09 
                 64.17 
                 116.41 
                 22.91 
                 121.52 
               
               
                 Kidney cancer cell 
               
               
                 ACHN 
                 −94.31 
                 24.97 
                 50.17 
                 46.52 
                 81.33 
               
               
                 SN12C 
                 −73.27 
                 68.53 
                 91.98 
                 64.65 
                 94.07 
               
               
                 UO-31 
                 −79.30 
                 23.94 
                 30.65 
                 51.45 
                 61.43 
               
               
                 Skin cancer cell 
               
               
                 LOX IMV1 
                 −50.6 
                 39.98 
                 61.88 
                 44.18 
                 96.94 
               
               
                 MALME-3M 
                 −71.54 
                 56.94 
                 155.47 
                 180.88 
                 149.83 
               
               
                 SK-MEL-2 
                 −73.16 
                 40.07 
                 8.04 
                 6.66 
                 21.96 
               
               
                 UACC-257 
                 −83.07 
                 39.69 
                 118.22 
                 91.06 
                 118.21 
               
               
                 UACC-62 
                 −82.32 
                 51.35 
                 67.58 
                 90.47 
                 95.25 
               
               
                 CNS cancer cell 
               
               
                 SF-539 
                 −47.11 
                 83.16 
                 93.56 
                 40.72 
                 101.16 
               
               
                 U251 
                 −89.26 
                 60.13 
                 87.84 
                 63.47 
                 95.92 
               
               
                 Mean 
                 2.68 
                 58.42 
                 80.41 
                 69.36 
                 100.83 
               
               
                 Delta 
                 102.68 
                 77.00 
                 83.21 
                 76.51 
                 115.91 
               
               
                 Range 
                 230.09 
                 120.88 
                 158.27 
                 188.03 
                 289.23 
               
               
                   
               
               
                 XXX: not detected 
               
             
          
         
       
     
         [0107]    The detailed in-vitro testing results of dose response of the Compound No. 22 obtained from National Cancer Institute Developmental Therapeutics Program are shown in Tables 3-1 to 3-9. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0108]    The detailed in-vitro testing results of dose response of the Compound No. 4 obtained from National Cancer Institute Developmental Therapeutics Program are shown in Tables 4-1 to 4-9. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0109]    The detailed in-vitro testing results of dose response of the Compound No. 25 obtained from National Cancer Institute Developmental Therapeutics Program are shown in Tables 5-1 to 5-9. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    
       
         
               
               
               
             
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
           
               
                   
                 TABLE 3-1 
               
             
             
               
                   
                   
               
               
                   
                 Log10 Concentration 
                   
               
             
          
           
               
                   
                 Time 
                 Mean Optical Densities 
                 Percent Growth 
                   
               
             
          
           
               
                 Panel/Cell Line 
                 Zero 
                 Ctrl 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 GI50 
                 TGI 
                 LC50 
               
               
                   
               
             
          
           
               
                 Leukemia 
               
             
          
           
               
                 CCRF-CEM 
                 0.445 
                 1.624 
                 1.589 
                 1.503 
                 1.323 
                 0.472 
                 0.470 
                 97 
                 90 
                 74 
                 2 
                 2 
                 2.18E−6 
                 &gt;1.00E−4  
                 &gt;1.00E−4 
               
               
                 HL-60(TB) 
                 0.744 
                 2.175 
                 2.214 
                 2.209 
                 2.079 
                 0.461 
                 0.421 
                 103 
                 102 
                 93 
                 −38 
                 −43 
                 2.14E−6 
                 5.13E−6 
                 &gt;1.00E−4 
               
               
                 K-562 
                 0.180 
                 1.220 
                 1.232 
                 1.174 
                 1.038 
                 0.375 
                 0.165 
                 101 
                 96 
                 83 
                 19 
                 −8 
                 3.23E−6 
                 4.92E−5 
                 &gt;1.00E−4 
               
               
                 MOLT-4 
                 0.455 
                 1.447 
                 1.444 
                 1.462 
                 1.199 
                 0.274 
                 0.280 
                 97 
                 99 
                 73 
                 −40 
                 −38 
                 1.59E−6 
                 4.43E−6 
                 &gt;1.00E−4 
               
               
                 RPMI-S226 
                 0.654 
                 1.899 
                 1.899 
                 1.820 
                 1.418 
                 0.653 
                 0.523 
                 100 
                 94 
                 61 
                 . 
                 −20 
                 1.53E−6 
                 9.91E−6 
                 &gt;1.00E−4 
               
               
                 SR 
                 0.167 
                 0.676 
                 0.718 
                 0.738 
                 0.669 
                 0.374 
                 0.278 
                 108 
                 112 
                 99 
                 41 
                 −22 
                 6.89E−6 
                 &gt;1.00E−4  
                 &gt;1.00E−4 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
               
               
             
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
           
               
                   
                 TABLE 3-2 
               
             
             
               
                   
                   
               
               
                   
                 Log10 Concentration 
                   
               
             
          
           
               
                   
                 Time 
                 Mean Optical Densities 
                 Percent Growth 
                   
               
             
          
           
               
                 Panel/Cell Line 
                 Zero 
                 Ctrl 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 GI50 
                 TGI 
                 LC50 
               
               
                   
               
             
          
           
               
                 Non-Small Cell Lung Cancer 
               
             
          
           
               
                 A549/ATCC 
                 0.110 
                 0.550 
                 0.566 
                 0.518 
                 0.513 
                 0.081 
                 0.091 
                 104 
                 93 
                 92 
                 −27 
                 −18 
                 2.25E−6 
                 5.94E−6 
                 &gt;1.00E−4 
               
               
                 EKVX 
                 0.652 
                 1.960 
                 1.914 
                 1.813 
                 1.745 
                 0.554 
                 0.251 
                 96 
                 89 
                 84 
                 −15 
                 −62 
                 2.19E−6 
                 7.03E−6 
                  5.65E−5 
               
               
                 HOP-62 
                 0.342 
                 1.187 
                 1.242 
                 1.242 
                 1.243 
                 0.380 
                 0.175 
                 107 
                 107 
                 107 
                 4 
                 −49 
                 3.59E−6 
                 1.21E−5 
                 &gt;1.00E−4 
               
               
                 HOP-92 
                 0.770 
                 1.201 
                 1.179 
                 1.150 
                 1.174 
                 0.765 
                 0.560 
                 95 
                 88 
                 94 
                 −1 
                 −27 
                 2.91E−6 
                 9.84E−6 
                 &gt;1.00E−4 
               
               
                 NCI-H226 
                 1.003 
                 1.740 
                 1.718 
                 1.701 
                 1.556 
                 1.467 
                 0.956 
                 97 
                 95 
                 75 
                 63 
                 −5 
                 1.56E−5 
                 8.53E−5 
                 &gt;1.00E−4 
               
               
                 NCI-H23 
                 0.418 
                 1.199 
                 1.209 
                 1.125 
                 0.775 
                 0.265 
                 0.271 
                 101 
                 91 
                 46 
                 −37 
                 −35 
                 8.02E−7 
                 3.59E−6 
                 &gt;1.00E−4 
               
               
                 NCI-H322M 
                 0.347 
                 0.840 
                 0.856 
                 0.922 
                 0.940 
                 0.890 
                 0.555 
                 103 
                 116 
                 120 
                 110 
                 42 
                 7.64E−5 
                 &gt;1.00E−4  
                 &gt;1.00E−4 
               
               
                 NCI-H460 
                 0.245 
                 1.818 
                 1.818 
                 1.767 
                 1.614 
                 0.116 
                 0.104 
                 100 
                 97 
                 87 
                 −53 
                 −58 
                 1.84E−6 
                 4.19E−6 
                  9.54E−6 
               
               
                 NCI-H522 
                 0.541 
                 2.032 
                 2.079 
                 2.073 
                 1.887 
                 0.634 
                 0.441 
                 103 
                 103 
                 90 
                 6 
                 −18 
                 3.01E−6 
                 1.78E−5 
                 &gt;1.00E−4 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
               
               
             
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
           
               
                   
                 TABLE 3-3 
               
             
             
               
                   
                   
               
               
                   
                 Log10 Concentration 
                   
               
             
          
           
               
                   
                 Time 
                 Mean Optical Densities 
                 Percent Growth 
                   
               
             
          
           
               
                 Panel/Cell Line 
                 Zero 
                 Ctrl 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 GI50 
                 TGI 
                 LC50 
               
               
                   
               
             
          
           
               
                 Colon Cancer 
               
             
          
           
               
                 COLO 205 
                 0.199 
                 0.969 
                 0.927 
                 0.872 
                 0.957 
                 0.069 
                 0.057 
                 95 
                 87 
                 98 
                 −66 
                 −71 
                 1.97E−6 
                 3.98E−6 
                 8.04E−6 
               
               
                 HCC-2998 
                 0.268 
                 0.572 
                 0.599 
                 0.581 
                 0.588 
                 0.098 
                 0.081 
                 109 
                 103 
                 105 
                 −63 
                 −70 
                 2.12E−6 
                 4.20E−6 
                 8.32E−6 
               
               
                 HCT-116 
                 0.138 
                 0.938 
                 0.927 
                 0.912 
                 0.863 
                 0.145 
                 0.095 
                 99 
                 97 
                 91 
                 1 
                 −31 
                 2.84E−6 
                 1.06E−5 
                 &gt;1.00E−4  
               
               
                 HCT-15 
                 0.285 
                 1.440 
                 1.554 
                 1.485 
                 1.323 
                 0.254 
                 0.138 
                 110 
                 104 
                 90 
                 −11 
                 −52 
                 2.49E−6 
                 7.80E−6 
                 9.06E−5 
               
               
                 HT29 
                 0.231 
                 1.387 
                 1.432 
                 1.444 
                 1.403 
                 0.195 
                 0.108 
                 104 
                 105 
                 101 
                 −16 
                 −53 
                 2.75E−6 
                 7.36E−6 
                 8.10E−5 
               
               
                 KM12 
                 0.217 
                 0.841 
                 0.884 
                 0.889 
                 0.861 
                 0.567 
                 0.103 
                 107 
                 108 
                 103 
                 56 
                 −53 
                 1.14E−5 
                 3.28E−5 
                 9.48E−5 
               
               
                 SW-620 
                 0.175 
                 1.174 
                 1.231 
                 1.201 
                 1.240 
                 0.633 
                 0.056 
                 106 
                 103 
                 107 
                 46 
                 −68 
                 8.55E−6 
                 2.52E−5 
                 6.92E−5 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
               
               
             
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
           
               
                   
                 TABLE 3-4 
               
             
             
               
                   
                   
               
               
                   
                 Log10 Concentration 
                   
               
             
          
           
               
                   
                 Time 
                 Mean Optical Densities 
                 Percent Growth 
                   
               
             
          
           
               
                 Panel/Cell Line 
                 Zero 
                 Ctrl 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 GI50 
                 TGI 
                 LC50 
               
               
                   
               
             
          
           
               
                 CNS Cancer 
               
             
          
           
               
                 SF-268 
                 0.357 
                 0.951 
                 0.959 
                 0.938 
                 0.893 
                 0.459 
                 0.193 
                 101 
                 98 
                 90 
                 17 
                 −46 
                 3.55E−6 
                 1.87E−5 
                 &gt;1.00E−4  
               
               
                 SF-295 
                 0.415 
                 1.524 
                 1.550 
                 1.579 
                 1.527 
                 0.404 
                 0.202 
                 102 
                 105 
                 100 
                 −3 
                 −51 
                 3.08E−6 
                 9.40E−6 
                 9.39E−5 
               
               
                 SF-539 
                 0.574 
                 1.690 
                 1.578 
                 1.517 
                 1.499 
                 0.006 
                 0.012 
                 90 
                 84 
                 83 
                 −99 
                 −98 
                 1.52E−6 
                 2.86E−6 
                 5.38E−6 
               
               
                 SNB-19 
                 0.464 
                 1.328 
                 1.349 
                 1.339 
                 1.330 
                 0.067 
                 0.008 
                 102 
                 101 
                 100 
                 −86 
                 −98 
                 1.86E−6 
                 3.46E−6 
                 6.43E−6 
               
               
                 SNB-75 
                 0.640 
                 1.050 
                 0.950 
                 0.911 
                 0.957 
                 −0.004 
                 −0.009 
                 76 
                 66 
                 77 
                 −100 
                 −100 
                 1.42E−6 
                 2.73E−6 
                 5.22E−6 
               
               
                 U251 
                 0.220 
                 1.137 
                 1.194 
                 1.177 
                 0.939 
                 0.086 
                 0.082 
                 106 
                 104 
                 78 
                 −61 
                 −63 
                 1.60E−6 
                 3.65E−6 
                 8.32E−6 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
               
               
             
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
           
               
                   
                 TABLE 3-5 
               
             
             
               
                   
                   
               
               
                   
                 Log10 Concentration 
                   
               
             
          
           
               
                   
                 Time 
                 Mean Optical Densities 
                 Percent Growth 
                   
               
             
          
           
               
                 Panel/Cell Line 
                 Zero 
                 Ctrl 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 GI50 
                 TGI 
                 LC50 
               
               
                   
               
             
          
           
               
                 Melanoma 
               
             
          
           
               
                 LOX IMVI 
                 0.363 
                 2.033 
                 2.046 
                 2.006 
                 1.219 
                 0.212 
                 0.244 
                 101 
                 98 
                 51 
                 −42 
                 −33 
                 1.03E−6 
                 3.56E−6 
                 &gt;1.00E−4  
               
               
                 MALME-3M 
                 0.229 
                 0.481 
                 0.487 
                 0.520 
                 0.512 
                 0.107 
                 0.065 
                 102 
                 115 
                 112 
                 −53 
                 −72 
                 2.37E−6 
                 4.76E−6 
                 9.55E−6 
               
               
                 M14 
                 0.339 
                 1.395 
                 1.398 
                 1.394 
                 1.411 
                 0.232 
                 0.199 
                 100 
                 100 
                 102 
                 −32 
                 −41 
                 2.44E−6 
                 5.78E−6 
                 &gt;1.00E−4  
               
               
                 SK-MEL-2 
                 0.284 
                 0.761 
                 0.810 
                 0.806 
                 0.731 
                 0.221 
                 0.194 
                 110 
                 109 
                 94 
                 −22 
                 −32 
                 2.38E−6 
                 6.42E−6 
                 &gt;1.00E−4  
               
               
                 SK-MEL-28 
                 0.300 
                 1.110 
                 1.135 
                 1.161 
                 1.165 
                 0.703 
                 0.023 
                 103 
                 106 
                 107 
                 50 
                 −93 
                 9.88E−6 
                 2.24E−5 
                 5.03E−5 
               
               
                 SK-MEL-5 
                 0.540 
                 2.145 
                 2.107 
                 1.896 
                 1.477 
                 −0.009 
                 −0.002 
                 98 
                 85 
                 58 
                 −100 
                 −100 
                 1.13E−6 
                 2.34E−6 
                 4.83E−6 
               
               
                 UACC-257 
                 0.493 
                 0.980 
                 0.962 
                 0.986 
                 0.870 
                 0.083 
                 0.047 
                 96 
                 101 
                 77 
                 −83 
                 −91 
                 1.48E−6 
                 3.03E−6 
                 6.21E−6 
               
               
                 UACC-62 
                 0.431 
                 1.918 
                 1.751 
                 1.787 
                 1.798 
                 0.331 
                 0.214 
                 89 
                 91 
                 92 
                 −23 
                 −50 
                 2.31E−6 
                 6.29E−6 
                 9.62E−6 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
               
               
             
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
           
               
                   
                 TABLE 3-6 
               
             
             
               
                   
                   
               
               
                   
                 Log10 Concentration 
                   
               
             
          
           
               
                   
                 Time 
                 Mean Optical Densities 
                 Percent Growth 
                   
               
             
          
           
               
                 Panel/Cell Line 
                 Zero 
                 Ctrl 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 GI50 
                 TGI 
                 LC50 
               
               
                   
               
             
          
           
               
                 Ovarian Cancer 
               
             
          
           
               
                 OVCAR-3 
                 0.305 
                 0.775 
                 0.852 
                 0.821 
                 0.710 
                 0.216 
                 0.075 
                 116 
                 110 
                 86 
                 −29 
                 −75 
                 2.06E−6 
                 5.59E−6 
                 2.82E−5 
               
               
                 OVCAR-4 
                 0.363 
                 0.880 
                 0.916 
                 0.850 
                 0.531 
                 −0.015 
                 −0.014 
                 107 
                 94 
                 32 
                 −100 
                 −100 
                 5.20E−7 
                 1.76E−6 
                 4.19E−6 
               
               
                 OVCAR-5 
                 0.446 
                 0.930 
                 0.924 
                 0.903 
                 0.953 
                 0.192 
                 0.187 
                 99 
                 94 
                 105 
                 −57 
                 −58 
                 2.18E−6 
                 4.44E−6 
                 9.06E−6 
               
               
                 OVCAR-8 
                 0.299 
                 1.154 
                 1.200 
                 1.171 
                 0.695 
                 0.169 
                 0.185 
                 105 
                 102 
                 46 
                 −43 
                 −38 
                 8.59E−7 
                 3.28E−6 
                 &gt;1.00E−4  
               
               
                 SK-OV-3 
                 0.530 
                 1.224 
                 1.239 
                 1.154 
                 1.150 
                 0.414 
                 0.015 
                 102 
                 90 
                 89 
                 −22 
                 −97 
                 2.26E−6 
                 6.35E−6 
                 2.36E−5 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
               
               
             
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
           
               
                   
                 TABLE 3-7 
               
             
             
               
                   
                   
               
               
                   
                 Log10 Concentration 
                   
               
             
          
           
               
                   
                 Time 
                 Mean Optical Densities 
                 Percent Growth 
                   
               
             
          
           
               
                 Panel/Cell Line 
                 Zero 
                 Ctrl 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 GI50 
                 TGI 
                 LC50 
               
               
                   
               
             
          
           
               
                 Renal Cancer 
               
             
          
           
               
                 786-0 
                 0.450 
                 1.828 
                 1.894 
                 1.916 
                 2.049 
                 0.517 
                 0.130 
                 105 
                 106 
                 116 
                 5 
                 −71 
                 3.93E−6 
                 1.16E−5 
                  5.27E−5 
               
               
                 A498 
                 0.605 
                 1.481 
                 1.527 
                 1.518 
                 1.449 
                 1.479 
                 1.340 
                 105 
                 104 
                 96 
                 100 
                 84 
                 &gt;1.00E−4  
                 &gt;1.00E−4  
                 &gt;1.00E−4 
               
               
                 ACHN 
                 0.355 
                 1.317 
                 1.389 
                 1.452 
                 1.220 
                 0.063 
                 0.218 
                 107 
                 114 
                 90 
                 −82 
                 −39 
                 1.71E−6 
                 3.33E−6 
                 . 
               
               
                 CAKI-1 
                 0.294 
                 0.870 
                 0.813 
                 0.844 
                 0.798 
                 0.226 
                 0.099 
                 90 
                 95 
                 88 
                 −23 
                 −66 
                 2.18E−6 
                 6.16E−6 
                  4.15E−5 
               
               
                 SN12C 
                 0.304 
                 1.076 
                 1.007 
                 1.097 
                 0.948 
                 0.284 
                 0.199 
                 91 
                 103 
                 83 
                 −7 
                 −35 
                 2.35E−6 
                 8.42E−6 
                 &gt;1.00E−4 
               
               
                 TK-10 
                 0.362 
                 0.792 
                 0.865 
                 0.935 
                 0.983 
                 0.868 
                 0.337 
                 117 
                 133 
                 144 
                 118 
                 −7 
                 3.49E−5 
                 8.80E−5 
                 &gt;1.00E−4 
               
               
                 UO-31 
                 0.147 
                 0.498 
                 0.539 
                 0.562 
                 0.499 
                 0.041 
                 0.050 
                 111 
                 118 
                 100 
                 −72 
                 −66 
                 1.95E−6 
                 3.81E−6 
                  7.41E−6 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
               
               
             
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
           
               
                   
                 TABLE 3-8 
               
             
             
               
                   
                   
               
               
                   
                 Log10 Concentration 
                   
               
             
          
           
               
                   
                 Time 
                 Mean Optical Densities 
                 Percent Growth 
                   
               
             
          
           
               
                 Panel/Cell Line 
                 Zero 
                 Ctrl 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 GI50 
                 TGI 
                 LC50 
               
               
                   
               
             
          
           
               
                 Prostate Cancer 
               
             
          
           
               
                 PC-3 
                 0.372 
                 1.158 
                 1.128 
                 1.096 
                 1.050 
                 0.459 
                 0.402 
                 96 
                 92 
                 86 
                 11 
                 4 
                 3.03E−6 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 DU-145 
                 0.230 
                 0.704 
                 0.750 
                 0.772 
                 0.752 
                 0.425 
                 −0.002 
                 110 
                 114 
                 110 
                 41 
                 −100 
                 7.41E−6 
                  1.95E−5 
                  4.42E−5 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
               
               
             
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
           
               
                   
                 TABLE 3-9 
               
             
             
               
                   
                   
               
               
                   
                 Log10 Concentration 
                   
               
             
          
           
               
                   
                 Time 
                 Mean Optical Densities 
                 Percent Growth 
                   
               
             
          
           
               
                 Panel/Cell Line 
                 Zero 
                 Ctrl 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 GI50 
                 TGI 
                 LC50 
               
               
                   
               
             
          
           
               
                 Breast Cancer 
               
             
          
           
               
                 MCF7 
                 0.282 
                 1.325 
                 1.202 
                 1.081 
                 0.929 
                 0.101 
                 0.104 
                 88 
                 77 
                 62 
                 −64 
                 −63 
                 1.24E−6 
                 3.10E−6 
                 7.72E−6 
               
               
                 NCI/ADR-RES 
                 0.436 
                 1.282 
                 1.343 
                 1.296 
                 0.608 
                 0.395 
                 0.363 
                 107 
                 102 
                 20 
                 −10 
                 −17 
                 4.32E−7 
                 4.80E−6 
                 &gt;1.00E−4  
               
               
                 MDA-MB-231/ATCC 
                 0.478 
                 1.197 
                 1.226 
                 1.100 
                 1.063 
                 0.510 
                 0.525 
                 104 
                 87 
                 81 
                 4 
                 6 
                 2.56E−6 
                 &gt;1.00E−4  
                 &gt;1.00E−4  
               
               
                 HS 578T 
                 0.413 
                 1.287 
                 1.362 
                 1.410 
                 1.289 
                 0.663 
                 0.595 
                 109 
                 114 
                 100 
                 29 
                 21 
                 5.03E−6 
                 &gt;1.00E−4  
                 &gt;1.00E−4  
               
               
                 MDA-MB-435 
                 0.280 
                 1.351 
                 1.350 
                 1.373 
                 1.160 
                 0.190 
                 0.137 
                 100 
                 102 
                 82 
                 −32 
                 −51 
                 1.91E−6 
                 5.23E−6 
                 8.78E−5 
               
               
                 BT-549 
                 0.254 
                 0.524 
                 0.503 
                 0.529 
                 0.594 
                 0.426 
                 0.122 
                 92 
                 102 
                 126 
                 64 
                 −52 
                 1.31E−5 
                 3.55E−5 
                 9.62E−5 
               
               
                 T-47D 
                 0.377 
                 0.816 
                 0.775 
                 0.763 
                 0.473 
                 0.156 
                 0.150 
                 91 
                 88 
                 22 
                 −59 
                 −60 
                 3.75E−7 
                 1.87E−6 
                 7.79E−6 
               
               
                 MDA-MB-468 
                 2.275 
                 3.124 
                 3.096 
                 3.134 
                 3.152 
                 0.022 
                 0.031 
                 97 
                 101 
                 103 
                 −99 
                 −99 
                 1.83E−6 
                 3.24E−6 
                 5.72E−6 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
               
               
             
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
           
               
                   
                 TABLE 4-1 
               
             
             
               
                   
                   
               
               
                   
                 Log10 Concentration 
                   
               
             
          
           
               
                   
                 Time 
                 Mean Optical Densities 
                 Percent Growth 
                   
               
             
          
           
               
                 Panel/Cell Line 
                 Zero 
                 Ctrl 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 GI50 
                 TGI 
                 LC50 
               
               
                   
               
             
          
           
               
                 Leukemia 
               
             
          
           
               
                 CCRF-CEM 
                 0.321 
                 1.468 
                 1.505 
                 1.400 
                 1.407 
                 0.910 
                 0.488 
                 103 
                 94 
                 95 
                 51 
                 15 
                 1.09E−5 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 HL-60(TB) 
                 0.691 
                 1.628 
                 1.626 
                 1.630 
                 1.639 
                 1.092 
                 0.873 
                 100 
                 100 
                 101 
                 43 
                 19 
                 7.53E−6 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 K-562 
                 0.269 
                 1.578 
                 1.498 
                 1.469 
                 1.412 
                 1.097 
                 0.903 
                 94 
                 92 
                 87 
                 63 
                 48 
                 7.83E−5 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 MOLT-4 
                 0.734 
                 2.108 
                 2.076 
                 2.057 
                 2.015 
                 1.402 
                 0.726 
                 98 
                 96 
                 93 
                 49 
                 −1 
                 9.31E−6 
                  9.51E−5 
                 &gt;1.00E−4 
               
               
                 RPMI-8226 
                 0.443 
                 1.284 
                 1.259 
                 1.121 
                 1.060 
                 0.547 
                 0.390 
                 97 
                 81 
                 73 
                 12 
                 −12 
                 2.42E−6 
                  3.21E−5 
                 &gt;1.00E−4 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
               
               
             
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
           
               
                   
                 TABLE 4-2 
               
             
             
               
                   
                   
               
               
                   
                 Log10 Concentration 
                   
               
             
          
           
               
                   
                 Time 
                 Mean Optical Densities 
                 Percent Growth 
                   
               
             
          
           
               
                 Panel/Cell Line 
                 Zero 
                 Ctrl 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 GI50 
                 TGI 
                 LC50 
               
               
                   
               
             
          
           
               
                 Non-Small Cell Lung Cancer 
               
             
          
           
               
                 A549/ATCC 
                 0.193 
                 0.895 
                 0.832 
                 0.892 
                 0.876 
                 0.614 
                 0.315 
                 91 
                 100 
                 97 
                 60 
                 17 
                 1.71E−5 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 EKVX 
                 0.897 
                 1.986 
                 1.856 
                 1.792 
                 1.540 
                 1.059 
                 0.894 
                 88 
                 82 
                 59 
                 15 
                 . 
                 1.60E−6 
                  9.43E−5 
                 &gt;1.00E−4 
               
               
                 HOP-62 
                 0.474 
                 1.375 
                 1.283 
                 1.318 
                 1.254 
                 1.127 
                 0.814 
                 90 
                 94 
                 87 
                 72 
                 38 
                 4.42E−5 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 HOP-92 
                 0.892 
                 1.397 
                 1.360 
                 1.297 
                 1.214 
                 1.134 
                 1.010 
                 93 
                 80 
                 64 
                 48 
                 23 
                 7.38E−6 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 NCI-H226 
                 0.817 
                 1.747 
                 1.612 
                 1.642 
                 1.608 
                 1.404 
                 1.022 
                 85 
                 89 
                 85 
                 63 
                 22 
                 2.08E−5 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 NCI-H23 
                 0.485 
                 1.638 
                 1.547 
                 1.500 
                 1.333 
                 1.051 
                 0.732 
                 92 
                 88 
                 74 
                 49 
                 21 
                 9.17E−6 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 NCI-H322M 
                 0.721 
                 1.844 
                 1.757 
                 1.746 
                 1.643 
                 1.177 
                 0.976 
                 92 
                 91 
                 82 
                 41 
                 23 
                 5.94E−6 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 NCI-H460 
                 0.233 
                 1.933 
                 1.666 
                 1.630 
                 1.494 
                 0.651 
                 0.266 
                 84 
                 82 
                 74 
                 25 
                 2 
                 3.07E−6 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 NCI-H522 
                 0.713 
                 2.605 
                 2.403 
                 2.370 
                 2.360 
                 1.735 
                 1.328 
                 89 
                 88 
                 87 
                 54 
                 32 
                 1.54E−5 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
               
               
             
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
           
               
                   
                 TABLE 4-3 
               
             
             
               
                   
                   
               
               
                   
                 Log10 Concentration 
                   
               
             
          
           
               
                   
                 Time 
                 Mean Optical Densities 
                 Percent Growth 
                   
               
             
          
           
               
                 Panel/Cell Line 
                 Zero 
                 Ctrl 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 GI50 
                 TGI 
                 LC50 
               
               
                   
               
             
          
           
               
                 Colon Cancer 
               
             
          
           
               
                 COLO 205 
                 0.213 
                 1.012 
                 0.960 
                 0.958 
                 0.891 
                 0.544 
                 0.284 
                 93 
                 93 
                 85 
                 41 
                 9 
                 6.36E−6 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 HCC-2998 
                 0.660 
                 2.134 
                 1.963 
                 2.044 
                 1.983 
                 1.527 
                 0.988 
                 88 
                 94 
                 90 
                 59 
                 22 
                 1.74E−5 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 HCT-116 
                 0.248 
                 2.129 
                 1.969 
                 2.043 
                 1.716 
                 1.044 
                 0.450 
                 92 
                 95 
                 78 
                 42 
                 11 
                 6.10E−6 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 HCT-15 
                 0.248 
                 1.514 
                 1.391 
                 1.422 
                 1.121 
                 0.588 
                 0.348 
                 90 
                 93 
                 69 
                 27 
                 8 
                 2.82E−6 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 HT29 
                 0.151 
                 0.999 
                 0.951 
                 0.998 
                 0.893 
                 0.557 
                 0.241 
                 94 
                 100 
                 88 
                 48 
                 11 
                 8.84E−6 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 KM12 
                 0.268 
                 1.092 
                 1.072 
                 1.040 
                 1.003 
                 0.625 
                 0.373 
                 98 
                 94 
                 89 
                 43 
                 13 
                 7.15E−6 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 SW-620 
                 0.150 
                 0.998 
                 0.991 
                 0.968 
                 0.902 
                 0.480 
                 0.202 
                 99 
                 96 
                 89 
                 39 
                 6 
                 5.97E−6 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
               
               
             
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
           
               
                   
                 TABLE 4-4 
               
             
             
               
                   
                   
               
               
                   
                 Log10 Concentration 
                   
               
             
          
           
               
                   
                 Time 
                 Mean Optical Densities 
                 Percent Growth 
                   
               
             
          
           
               
                 Panel/Cell Line 
                 Zero 
                 Ctrl 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 GI50 
                 TGI 
                 LC50 
               
               
                   
               
             
          
           
               
                 CNS Cancer 
               
             
          
           
               
                 SF-268 
                 0.319 
                 1.084 
                 0.986 
                 1.053 
                 0.990 
                 0.758 
                 0.530 
                 87 
                 96 
                 88 
                 57 
                 28 
                 1.77E−5 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 SF-295 
                 0.695 
                 1.929 
                 1.785 
                 1.806 
                 1.549 
                 1.127 
                 0.812 
                 88 
                 90 
                 69 
                 35 
                 9 
                 3.65E−6 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 SF-539 
                 0.639 
                 1.878 
                 1.642 
                 1.666 
                 1.631 
                 1.204 
                 0.798 
                 81 
                 83 
                 80 
                 46 
                 13 
                 7.46E−6 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 SNB-19 
                 0.656 
                 1.341 
                 1.229 
                 1.299 
                 1.289 
                 1.073 
                 0.921 
                 84 
                 94 
                 92 
                 61 
                 39 
                 3.09E−5 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 SNB-75 
                 0.661 
                 1.282 
                 1.068 
                 1.070 
                 0.965 
                 0.916 
                 0.770 
                 66 
                 66 
                 49 
                 41 
                 17 
                 8.72E−7 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 U251 
                 0.280 
                 1.443 
                 1.369 
                 1.393 
                 1.260 
                 0.854 
                 0.597 
                 94 
                 96 
                 84 
                 49 
                 27 
                 9.58E−6 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
               
               
             
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
           
               
                   
                 TABLE 4-5 
               
             
             
               
                   
                   
               
               
                   
                 Log10 Concentration 
                   
               
             
          
           
               
                   
                 Time 
                 Mean Optical Densities 
                 Percent Growth 
                   
               
             
          
           
               
                 Panel/Cell Line 
                 Zero 
                 Ctrl 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 GI50 
                 TGI 
                 LC50 
               
               
                   
               
             
          
           
               
                 Melanoma 
               
             
          
           
               
                 LOX IMVI 
                 0.316 
                 2.231 
                 2.245 
                 2.058 
                 1.903 
                 0.956 
                 0.508 
                 101 
                 91 
                 83 
                 33 
                 10 
                 4.61E−6 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 MALME-3M 
                 0.694 
                 1.247 
                 1.174 
                 1.161 
                 1.153 
                 0.835 
                 0.683 
                 87 
                 84 
                 83 
                 26 
                 −2 
                 3.75E−6 
                  8.69E−5 
                 &gt;1.00E−4 
               
               
                 M14 
                 0.435 
                 1.796 
                 1.627 
                 1.731 
                 1.500 
                 1.119 
                 0.776 
                 88 
                 95 
                 78 
                 50 
                 25 
                 1.02E−5 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 SK-MEL-28 
                 0.239 
                 0.861 
                 0.794 
                 0.762 
                 0.730 
                 0.537 
                 0.211 
                 89 
                 84 
                 79 
                 48 
                 −12 
                 8.58E−6 
                  6.36E−5 
                 &gt;1.00E−4 
               
               
                 SK-MEL-5 
                 0.639 
                 2.089 
                 1.284 
                 1.249 
                 1.501 
                 0.607 
                 0.515 
                 44 
                 42 
                 59 
                 −5 
                 −19 
                 . 
                  8.36E−6 
                 &gt;1.00E−4 
               
               
                 UACC-257 
                 0.437 
                 0.825 
                 0.763 
                 0.761 
                 0.808 
                 0.694 
                 0.506 
                 84 
                 84 
                 96 
                 66 
                 18 
                 2.16E−5 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 UACC-62 
                 0.639 
                 2.092 
                 1.844 
                 1.978 
                 1.874 
                 1.231 
                 1.015 
                 83 
                 92 
                 85 
                 41 
                 26 
                 6.18E−6 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
               
               
             
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
           
               
                   
                 TABLE 4-6 
               
             
             
               
                   
                   
               
               
                   
                 Log10 Concentration 
                   
               
             
          
           
               
                   
                 Time 
                 Mean Optical Densities 
                 Percent Growth 
                   
               
             
          
           
               
                 Panel/Cell Line 
                 Zero 
                 Ctrl 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 GI50 
                 TGI 
                 LC50 
               
               
                   
               
             
          
           
               
                 Ovarian Cancer 
               
             
          
           
               
                 IGROV1 
                 0.518 
                 1.681 
                 1.555 
                 1.537 
                 1.174 
                 0.583 
                 0.421 
                 89 
                 88 
                 56 
                 6 
                 −19 
                 1.34E−6 
                  1.69E−5 
                 &gt;1.00E−4 
               
               
                 OVCAR-3 
                 0.283 
                 0.746 
                 0.745 
                 0.773 
                 0.713 
                 0.549 
                 0.319 
                 100 
                 106 
                 93 
                 57 
                 8 
                 1.41E−5 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 OVCAR-4 
                 0.565 
                 1.740 
                 1.719 
                 1.694 
                 1.535 
                 0.999 
                 0.745 
                 98 
                 96 
                 83 
                 37 
                 15 
                 5.18E−6 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 OVCAR-5 
                 0.395 
                 0.931 
                 0.865 
                 0.884 
                 0.900 
                 0.852 
                 0.637 
                 88 
                 91 
                 94 
                 85 
                 45 
                 7.57E−5 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 OVCAR-8 
                 0.228 
                 0.904 
                 0.881 
                 0.841 
                 0.847 
                 0.623 
                 0.393 
                 96 
                 91 
                 92 
                 58 
                 24 
                 1.77E−5 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 SK-OV-3 
                 0.566 
                 1.432 
                 1.392 
                 1.359 
                 1.223 
                 0.673 
                 0.687 
                 95 
                 92 
                 76 
                 12 
                 14 
                 2.55E−6 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
               
               
             
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
           
               
                   
                 TABLE 4-7 
               
             
             
               
                   
                   
               
               
                   
                 Log10 Concentration 
                   
               
             
          
           
               
                   
                 Time 
                 Mean Optical Densities 
                 Percent Growth 
                   
               
             
          
           
               
                 Panel/Cell Line 
                 Zero 
                 Ctrl 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 GI50 
                 TGI 
                 LC50 
               
               
                   
               
             
          
           
               
                 Renal Cancer 
               
             
          
           
               
                 786-0 
                 0.664 
                 2.228 
                 2.288 
                 2.259 
                 2.143 
                 1.725 
                 1.264 
                 104 
                 102 
                 95 
                 68 
                 38 
                 4.02E−5 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 A498 
                 0.564 
                 1.224 
                 1.202 
                 1.221 
                 1.065 
                 0.793 
                 0.453 
                 94 
                 97 
                 74 
                 34 
                 −20 
                 3.89E−6 
                  4.27E−5 
                 &gt;1.00E−4 
               
               
                 ACHN 
                 0.385 
                 1.455 
                 1.393 
                 1.299 
                 1.047 
                 0.537 
                 0.366 
                 94 
                 85 
                 62 
                 14 
                 −5 
                 1.77E−6 
                  5.46E−5 
                 &gt;1.00E−4 
               
               
                 CAKI-1 
                 0.547 
                 1.711 
                 1.680 
                 1.610 
                 1.430 
                 0.780 
                 0.654 
                 97 
                 91 
                 76 
                 20 
                 9 
                 2.90E−6 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 SN12C 
                 0.617 
                 1.996 
                 1.639 
                 1.719 
                 1.640 
                 1.247 
                 0.872 
                 74 
                 80 
                 74 
                 46 
                 18 
                 7.05E−6 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 TK-10 
                 0.612 
                 1.245 
                 1.212 
                 1.327 
                 1.088 
                 0.856 
                 0.633 
                 95 
                 113 
                 75 
                 39 
                 3 
                 4.88E−6 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 UO-31 
                 0.517 
                 1.634 
                 1.496 
                 1.444 
                 1.268 
                 0.680 
                 0.518 
                 88 
                 83 
                 67 
                 15 
                 . 
                 2.12E−6 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
               
               
             
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
           
               
                   
                 TABLE 4-8 
               
             
             
               
                   
                   
               
               
                   
                 Log10 Concentration 
                   
               
             
          
           
               
                   
                 Time 
                 Mean Optical Densities 
                 Percent Growth 
                   
               
             
          
           
               
                 Panel/Cell Line 
                 Zero 
                 Ctrl 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 GI50 
                 TGI 
                 LC50 
               
               
                   
               
             
          
           
               
                 Prostate Cancer 
               
             
          
           
               
                 PC-3 
                 0.306 
                 1.233 
                 1.197 
                 1.233 
                 1.170 
                 0.807 
                 0.572 
                 96 
                 100 
                 93 
                 54 
                 29 
                 1.44E−5 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 DU-145 
                 0.226 
                 0.724 
                 0.713 
                 0.713 
                 0.666 
                 0.411 
                 0.344 
                 98 
                 98 
                 88 
                 37 
                 24 
                 5.62E−6 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
               
               
             
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
           
               
                   
                 TABLE 4-9 
               
             
             
               
                   
                   
               
               
                   
                 Log10 Concentration 
                   
               
             
          
           
               
                   
                 Time 
                 Mean Optical Densities 
                 Percent Growth 
                   
               
             
          
           
               
                 Panel/Cell Line 
                 Zero 
                 Ctrl 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 GI50 
                 TGI 
                 LC50 
               
               
                   
               
             
          
           
               
                 Breast Cancer 
               
             
          
           
               
                 MCF7 
                 0.249 
                 1.082 
                 0.960 
                 0.880 
                 0.697 
                 0.556 
                 0.240 
                 85 
                 76 
                 54 
                 37 
                 −4 
                 1.68E−6 
                  8.14E−5 
                 &gt;1.00E−4 
               
               
                 NCI/ADR-RES 
                 0.461 
                 1.540 
                 1.483 
                 1.524 
                 1.421 
                 1.010 
                 0.530 
                 95 
                 99 
                 89 
                 51 
                 6 
                 1.05E−5 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 MDA-MB-231/ATCC 
                 0.453 
                 1.133 
                 1.121 
                 1.097 
                 1.063 
                 0.820 
                 0.700 
                 98 
                 95 
                 90 
                 54 
                 36 
                 1.66E−5 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 HS 578T 
                 0.296 
                 0.704 
                 0.734 
                 0.736 
                 0.526 
                 0.393 
                 0.202 
                 107 
                 108 
                 56 
                 24 
                 −32 
                 1.56E−6 
                  2.67E−5 
                 &gt;1.00E−4 
               
               
                 MDA-MB-435 
                 0.515 
                 1.859 
                 1.815 
                 1.744 
                 1.748 
                 1.404 
                 1.019 
                 97 
                 91 
                 92 
                 66 
                 37 
                 3.65E−5 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 BT-549 
                 1.015 
                 2.001 
                 2.009 
                 2.006 
                 1.951 
                 1.606 
                 1.166 
                 101 
                 100 
                 95 
                 60 
                 15 
                 1.67E−5 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 T-47D 
                 0.415 
                 0.852 
                 0.876 
                 0.824 
                 0.755 
                 0.554 
                 0.459 
                 105 
                 94 
                 78 
                 32 
                 10 
                 4.00E−6 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 MDA-MB-468 
                 0.494 
                 1.038 
                 0.944 
                 0.977 
                 0.923 
                 0.654 
                 0.458 
                 83 
                 89 
                 79 
                 29 
                 −7 
                 3.83E−6 
                  6.33E−5 
                 &gt;1.00E−4 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
               
               
             
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
           
               
                   
                 TABLE 5-1 
               
             
             
               
                   
                   
               
               
                   
                 Log10 Concentration 
                   
               
             
          
           
               
                   
                 Time 
                 Mean Optical Densities 
                 Percent Growth 
                   
               
             
          
           
               
                 Panel/Cell Line 
                 Zero 
                 Ctrl 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 GI50 
                 TGI 
                 LC50 
               
               
                   
               
             
          
           
               
                 Leukemia 
               
             
          
           
               
                 CCRF-CEM 
                 0.230 
                 0.806 
                 0.751 
                 0.755 
                 0.622 
                 0.358 
                 0.344 
                 90 
                 91 
                 68 
                 22 
                 20 
                 2.46E−6 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 HL-60(TB) 
                 0.336 
                 0.640 
                 0.587 
                 0.540 
                 0.478 
                 0.347 
                 0.153 
                 83 
                 67 
                 47 
                 3 
                 −54 
                 6.77E−7 
                  1.15E−5 
                  8.37E−5 
               
               
                 K-562 
                 0.086 
                 0.900 
                 0.851 
                 0.422 
                 0.332 
                 0.225 
                 0.166 
                 94 
                 41 
                 30 
                 17 
                 10 
                 6.83E−8 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 MOLT-4 
                 0.273 
                 1.048 
                 0.959 
                 0.900 
                 0.830 
                 0.529 
                 0.302 
                 89 
                 81 
                 72 
                 33 
                 4 
                 3.65E−6 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 RPMI-8226 
                 0.429 
                 1.331 
                 1.245 
                 1.161 
                 0.926 
                 0.702 
                 0.535 
                 90 
                 81 
                 55 
                 30 
                 12 
                 1.61E−6 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
               
               
             
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
           
               
                   
                 TABLE 5-2 
               
             
             
               
                   
                   
               
               
                   
                 Log10 Concentration 
                   
               
             
          
           
               
                   
                 Time 
                 Mean Optical Densities 
                 Percent Growth 
                   
               
             
          
           
               
                 Panel/Cell Line 
                 Zero 
                 Ctrl 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 GI50 
                 TGI 
                 LC50 
               
               
                   
               
             
          
           
               
                 Non-Small Cell Lung Cancer 
               
             
          
           
               
                 A549/ATCC 
                 0.551 
                 1.857 
                 1.771 
                 1.792 
                 1.552 
                 1.022 
                 0.594 
                 93 
                 95 
                 77 
                 36 
                 3 
                 4.53E−6 
                 &gt;1.00E−4  
                 &gt;1.00E−4 
               
               
                 EKVX 
                 0.439 
                 1.025 
                 1.032 
                 0.960 
                 0.904 
                 0.584 
                 0.421 
                 101 
                 89 
                 79 
                 25 
                 −4 
                 3.45E−6 
                 7.21E−5 
                 &gt;1.00E−4 
               
               
                 HOP-62 
                 0.233 
                 0.934 
                 0.879 
                 0.811 
                 0.799 
                 0.512 
                 0.255 
                 92 
                 82 
                 81 
                 40 
                 3 
                 5.64E−6 
                 &gt;1.00E−4  
                 &gt;1.00E−4 
               
               
                 HOP-92 
                 0.785 
                 1.360 
                 1.334 
                 1.260 
                 1.231 
                 1.206 
                 0.829 
                 95 
                 83 
                 78 
                 73 
                 8 
                 2.25E−5 
                 &gt;1.00E−4  
                 &gt;1.00E−4 
               
               
                 NCI-H226 
                 0.780 
                 1.765 
                 1.631 
                 1.577 
                 1.497 
                 1.415 
                 0.769 
                 86 
                 81 
                 73 
                 64 
                 −1 
                 1.66E−5 
                 9.52E−5 
                 &gt;1.00E−4 
               
               
                 NCI-H23 
                 0.452 
                 1.356 
                 1.281 
                 1.242 
                 1.213 
                 0.950 
                 0.407 
                 92 
                 87 
                 84 
                 55 
                 −10 
                 1.20E−5 
                 7.03E−5 
                 &gt;1.00E−4 
               
               
                 NCI-H322M 
                 0.310 
                 0.751 
                 0.736 
                 0.709 
                 0.722 
                 0.592 
                 0.307 
                 96 
                 90 
                 93 
                 64 
                 −1 
                 1.63E−5 
                 9.61E−5 
                 &gt;1.00E−4 
               
               
                 NCI-H460 
                 0.229 
                 1.901 
                 1.869 
                 1.815 
                 1.309 
                 0.507 
                 0.179 
                 98 
                 95 
                 65 
                 17 
                 −22 
                 2.01E−6 
                 2.69E−5 
                 &gt;1.00E−4 
               
               
                 NCI-H522 
                 0.336 
                 1.040 
                 0.966 
                 0.942 
                 0.906 
                 0.579 
                 0.226 
                 89 
                 86 
                 81 
                 35 
                 −33 
                 4.64E−6 
                 3.25E−5 
                 &gt;1.00E−4 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
               
               
             
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
           
               
                   
                 TABLE 5-3 
               
             
             
               
                   
                   
               
               
                   
                 Log10 Concentration 
                   
               
             
          
           
               
                   
                 Time 
                 Mean Optical Densities 
                 Percent Growth 
                   
               
             
          
           
               
                 Panel/Cell Line 
                 Zero 
                 Ctrl 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 GI50 
                 TGI 
                 LC50 
               
               
                   
               
             
          
           
               
                 Colon Cancer 
               
             
          
           
               
                 COLO 205 
                 0.211 
                 0.782 
                 0.739 
                 0.704 
                 0.634 
                 0.376 
                 0.138 
                 92 
                 86 
                 74 
                 29 
                 −35 
                 3.40E−6 
                 2.84E−5 
                 &gt;1.00E−4 
               
               
                 HCC-2998 
                 0.326 
                 1.161 
                 1.135 
                 1.113 
                 0.759 
                 0.658 
                 0.315 
                 97 
                 94 
                 52 
                 40 
                 −3 
                 1.40E−6 
                 8.35E−5 
                 &gt;1.00E−4 
               
               
                 HCT-116 
                 0.142 
                 1.101 
                 1.060 
                 1.089 
                 1.018 
                 0.666 
                 0.175 
                 96 
                 99 
                 91 
                 55 
                 3 
                 1.23E−5 
                 &gt;1.00E−4  
                 &gt;1.00E−4 
               
               
                 HCT-15 
                 0.274 
                 1.667 
                 1.502 
                 1.449 
                 1.343 
                 0.784 
                 0.266 
                 88 
                 84 
                 77 
                 37 
                 −3 
                 4.63E−6 
                 8.43E−5 
                 &gt;1.00E−4 
               
               
                 HT29 
                 0.174 
                 1.186 
                 1.176 
                 1.131 
                 0.925 
                 0.636 
                 0.184 
                 99 
                 95 
                 74 
                 46 
                 1 
                 7.01E−6 
                 &gt;1.00E−4  
                 &gt;1.00E−4 
               
               
                 KM12 
                 0.224 
                 0.967 
                 0.884 
                 0.896 
                 0.786 
                 0.522 
                 0.185 
                 89 
                 90 
                 76 
                 40 
                 −18 
                 5.26E−6 
                 4.95E−5 
                 &gt;1.00E−4 
               
               
                 SW-620 
                 0.159 
                 1.008 
                 0.960 
                 0.901 
                 0.649 
                 0.369 
                 0.118 
                 94 
                 87 
                 58 
                 25 
                 −26 
                 1.71E−6 
                 3.08E−5 
                 &gt;1.00E−4 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
               
               
             
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
           
               
                   
                 TABLE 5-4 
               
             
             
               
                   
                   
               
               
                   
                 Log10 Concentration 
                   
               
             
          
           
               
                   
                 Time 
                 Mean Optical Densities 
                 Percent Growth 
                   
               
             
          
           
               
                 Panel/Cell Line 
                 Zero 
                 Ctrl 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 GI50 
                 TGI 
                 LC50 
               
               
                   
               
             
          
           
               
                 CNS Cancer 
               
             
          
           
               
                 SF-268 
                 0.347 
                 1.080 
                 1.051 
                 1.020 
                 0.981 
                 0.598 
                 0.357 
                 96 
                 92 
                 86 
                 34 
                 1 
                 4.98E−6 
                 &gt;1.00E−4  
                 &gt;1.00E−4 
               
               
                 SF-295 
                 0.598 
                 1.530 
                 1.440 
                 1.375 
                 1.481 
                 0.828 
                 0.456 
                 90 
                 83 
                 95 
                 25 
                 −24 
                 4.35E−6 
                 3.23E−5 
                 &gt;1.00E−4 
               
               
                 SF-539 
                 0.657 
                 1.869 
                 1.748 
                 1.719 
                 1.430 
                 0.937 
                 0.601 
                 90 
                 88 
                 64 
                 23 
                 −9 
                 2.18E−6 
                 5.37E−5 
                 &gt;1.00E−4 
               
               
                 SNB-19 
                 0.279 
                 0.934 
                 0.892 
                 0.887 
                 0.867 
                 0.650 
                 0.307 
                 94 
                 93 
                 90 
                 57 
                 4 
                 1.34E−5 
                 &gt;1.00E−4  
                 &gt;1.00E−4 
               
               
                 SNB-75 
                 0.649 
                 1.457 
                 1.324 
                 1.350 
                 1.264 
                 1.079 
                 0.740 
                 83 
                 87 
                 76 
                 53 
                 11 
                 1.19E−5 
                 &gt;1.00E−4  
                 &gt;1.00E−4 
               
               
                 U251 
                 0.231 
                 1.283 
                 1.242 
                 1.205 
                 1.172 
                 0.604 
                 0.184 
                 96 
                 93 
                 89 
                 35 
                 −21 
                 5.38E−6 
                 4.29E−5 
                 &gt;1.00E−4 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
               
               
             
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
           
               
                   
                 TABLE 5-5 
               
             
             
               
                   
                   
               
               
                   
                 Log10 Concentration 
                   
               
             
          
           
               
                   
                 Time 
                 Mean Optical Densities 
                 Percent Growth 
                   
               
             
          
           
               
                 Panel/Cell Line 
                 Zero 
                 Ctrl 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 GI50 
                 TGI 
                 LC50 
               
               
                   
               
             
          
           
               
                 Melanoma 
               
             
          
           
               
                 LOX IMVT 
                 0.311 
                 2.100 
                 1.927 
                 1.830 
                 1.766 
                 0.867 
                 0.244 
                 90 
                 85 
                 81 
                 31 
                 −22 
                 4.20E−6 
                 3.89E−5 
                 &gt;1.00E−4 
               
               
                 MALME-3M 
                 0.403 
                 0.725 
                 0.715 
                 0.696 
                 0.687 
                 0.498 
                 0.145 
                 97 
                 91 
                 88 
                 30 
                 −64 
                 4.48E−6 
                 2.07E−5 
                  7.08E−5 
               
               
                 M14 
                 0.352 
                 1.249 
                 1.202 
                 1.164 
                 1.149 
                 0.659 
                 0.356 
                 95 
                 91 
                 89 
                 34 
                 . 
                 5.14E−6 
                 &gt;1.00E−4  
                 &gt;1.00E−4 
               
               
                 SK-MEL-2 
                 0.212 
                 0.515 
                 0.505 
                 0.471 
                 0.521 
                 0.388 
                 0.171 
                 97 
                 85 
                 102 
                 58 
                 −20 
                 1.27E−5 
                 5.59E−5 
                 &gt;1.00E−4 
               
               
                 SK-MEL-28 
                 0.363 
                 1.041 
                 1.041 
                 1.050 
                 1.070 
                 0.873 
                 0.352 
                 100 
                 101 
                 104 
                 75 
                 −3 
                 2.10E−5 
                 9.11E−5 
                 &gt;1.00E−4 
               
               
                 SK-MEL-5 
                 0.644 
                 2.455 
                 2.270 
                 2.280 
                 2.136 
                 1.150 
                 0.049 
                 90 
                 90 
                 82 
                 28 
                 −92 
                 3.93E−6 
                 1.71E−5 
                  4.44E−5 
               
               
                 UACC-257 
                 0.466 
                 1.070 
                 1.040 
                 0.996 
                 1.063 
                 0.815 
                 0.413 
                 95 
                 88 
                 99 
                 58 
                 −11 
                 1.30E−5 
                 6.83E−5 
                 &gt;1.00E−4 
               
               
                 UACC-62 
                 0.828 
                 2.206 
                 2.103 
                 1.986 
                 2.030 
                 1.655 
                 0.662 
                 92 
                 84 
                 87 
                 60 
                 −20 
                 1.33E−5 
                 5.61E−5 
                 &gt;1.00E−4 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
               
               
             
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
           
               
                   
                 TABLE 5-6 
               
             
             
               
                   
                   
               
               
                   
                 Log10 Concentration 
                   
               
             
          
           
               
                   
                 Time 
                 Mean Optical Densities 
                 Percent Growth 
                   
               
             
          
           
               
                 Panel/Cell Line 
                 Zero 
                 Ctrl 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 GI50 
                 TGI 
                 LC50 
               
               
                   
               
             
          
           
               
                 Ovarian Cancer 
               
             
          
           
               
                 IGROV1 
                 0.313 
                 1.001 
                 0.932 
                 0.824 
                 0.735 
                 0.543 
                 0.229 
                 90 
                 74 
                 61 
                 33 
                 −27 
                 2.55E−6 
                  3.59E−5 
                 &gt;1.00E−4 
               
               
                 OVCAR-3 
                 0.237 
                 0.743 
                 0.766 
                 0.717 
                 0.626 
                 0.260 
                 0.137 
                 104 
                 95 
                 77 
                 4 
                 −42 
                 2.34E−6 
                  1.25E−5 
                 &gt;1.00E−4 
               
               
                 OVCAR-4 
                 0.449 
                 1.297 
                 1.311 
                 1.220 
                 1.075 
                 0.883 
                 0.472 
                 102 
                 91 
                 74 
                 51 
                 3 
                 1.05E−5 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 OVCAR-5 
                 0.372 
                 1.072 
                 1.054 
                 0.999 
                 1.056 
                 0.912 
                 0.506 
                 97 
                 90 
                 98 
                 77 
                 19 
                 5.93E−5 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 OVCAR-8 
                 0.271 
                 1.191 
                 1.163 
                 1.091 
                 1.031 
                 0.606 
                 0.390 
                 97 
                 89 
                 83 
                 36 
                 13 
                 5.07E−6 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 SK-OV-3 
                 0.521 
                 1.313 
                 1.243 
                 1.228 
                 1.150 
                 0.874 
                 0.586 
                 91 
                 89 
                 79 
                 44 
                 8 
                 6.95E−6 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
               
               
             
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
           
               
                   
                 TABLE 5-7 
               
             
             
               
                   
                   
               
               
                   
                 Log10 Concentration 
                   
               
             
          
           
               
                   
                 Time 
                 Mean Optical Densities 
                 Percent Growth 
                   
               
             
          
           
               
                 Panel/Cell Line 
                 Zero 
                 Ctrl 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 GI50 
                 TGI 
                 LC50 
               
               
                   
               
             
          
           
               
                 Renal Cancer 
               
             
          
           
               
                 786-0 
                 0.611 
                 2.118 
                 2.089 
                 2.131 
                 2.186 
                 1.320 
                 0.835 
                 98 
                 101 
                 104 
                 47 
                 15 
                 8.87E−6 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 A498 
                 0.575 
                 1.116 
                 1.079 
                 1.034 
                 1.058 
                 0.839 
                 0.456 
                 93 
                 85 
                 89 
                 49 
                 −21 
                 9.31E−6 
                  5.03E−5 
                 &gt;1.00E−4 
               
               
                 ACHN 
                 0.370 
                 1.672 
                 1.642 
                 1.508 
                 1.367 
                 0.776 
                 0.397 
                 98 
                 87 
                 77 
                 31 
                 2 
                 3.85E−6 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 CAKI-1 
                 0.369 
                 1.388 
                 1.325 
                 1.271 
                 1.260 
                 0.762 
                 0.409 
                 94 
                 89 
                 87 
                 39 
                 4 
                 5.83E−6 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 RXF 393 
                 0.826 
                 2.065 
                 2.024 
                 1.973 
                 1.829 
                 1.355 
                 0.919 
                 97 
                 93 
                 81 
                 43 
                 7 
                 6.43E−6 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 SN12C 
                 0.518 
                 1.551 
                 1.421 
                 1.257 
                 1.326 
                 1.108 
                 0.508 
                 87 
                 71 
                 78 
                 57 
                 −2 
                 1.32E−5 
                  9.27E−5 
                 &gt;1.00E−4 
               
               
                 TK-10 
                 0.190 
                 0.513 
                 0.518 
                 0.464 
                 0.457 
                 0.306 
                 0.196 
                 102 
                 85 
                 83 
                 36 
                 2 
                 5.00E−6 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 UO-31 
                 0.483 
                 1.268 
                 1.113 
                 1.058 
                 1.059 
                 0.678 
                 0.475 
                 80 
                 73 
                 73 
                 25 
                 −2 
                 3.02E−6 
                  8.59E−5 
                 &gt;1.00E−4 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
               
               
             
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
           
               
                   
                 TABLE 5-8 
               
             
             
               
                   
                   
               
               
                   
                 Log10 Concentration 
                   
               
             
          
           
               
                   
                 Time 
                 Mean Optical Densities 
                 Percent Growth 
                   
               
             
          
           
               
                 Panel/Cell Line 
                 Zero 
                 Ctrl 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 GI50 
                 TGI 
                 LC50 
               
               
                   
               
             
          
           
               
                 Prostate Cancer 
               
             
          
           
               
                 PC-3 
                 0.138 
                 0.476 
                 0.479 
                 0.449 
                 0.373 
                 0.306 
                 0.308 
                 101 
                 92 
                 69 
                 50 
                 50 
                 . 
                 &gt;1.00E−4 
                 &gt;1.00E−4 
               
               
                 DU-145 
                 0.200 
                 0.762 
                 0.775 
                 0.735 
                 0.739 
                 0.515 
                 0.103 
                 102 
                 95 
                 96 
                 56 
                 −49 
                 1.14E−5 
                  3.43E−5 
                 &gt;1.00E−4 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
               
               
             
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
           
               
                   
                 TABLE 5-9 
               
             
             
               
                   
                   
               
               
                   
                 Log10 Concentration 
                   
               
             
          
           
               
                   
                 Time 
                 Mean Optical Densities 
                 Percent Growth 
                   
               
             
          
           
               
                 Panel/Cell Line 
                 Zero 
                 Ctrl 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 −8.0 
                 −7.0 
                 −6.0 
                 −5.0 
                 −4.0 
                 GI50 
                 TGI 
                 LC50 
               
               
                   
               
             
          
           
               
                 Breast Cancer 
               
             
          
           
               
                 MCF7 
                 0.451 
                 2.118 
                 1.797 
                 1.793 
                 1.201 
                 0.894 
                 0.318 
                 81 
                 80 
                 45 
                 27 
                 −29 
                 7.22E−7 
                 2.98E−5 
                 &gt;1.00E−4 
               
               
                 NCI/ADR-RES 
                 0.476 
                 1.685 
                 1.621 
                 1.586 
                 1.530 
                 0.934 
                 0.567 
                 95 
                 92 
                 87 
                 38 
                 8 
                 5.68E−6 
                 &gt;1.00E−4  
                 &gt;1.00E−4 
               
               
                 MDA-MB-231/ATCC 
                 0.444 
                 1.084 
                 1.085 
                 1.008 
                 0.987 
                 0.854 
                 0.535 
                 100 
                 88 
                 85 
                 64 
                 14 
                 1.91E−5 
                 &gt;1.00E−4  
                 &gt;1.00E−4 
               
               
                 HS 578T 
                 0.415 
                 0.913 
                 0.854 
                 0.861 
                 0.819 
                 0.710 
                 0.405 
                 88 
                 90 
                 81 
                 59 
                 −2 
                 1.41E−5 
                 9.14E−5 
                 &gt;1.00E−4 
               
               
                 MDA-MB-435 
                 0.426 
                 1.511 
                 1.527 
                 1.479 
                 1.525 
                 1.043 
                 0.021 
                 101 
                 97 
                 101 
                 57 
                 −95 
                 1.11E−5 
                 2.37E−5 
                  5.04E−5 
               
               
                 BT-549 
                 0.571 
                 1.144 
                 1.114 
                 1.057 
                 1.044 
                 0.886 
                 0.562 
                 95 
                 85 
                 83 
                 55 
                 −2 
                 1.22E−5 
                 9.35E−5 
                 &gt;1.00E−4 
               
               
                 T-47D 
                 0.393 
                 0.891 
                 0.819 
                 0.794 
                 0.747 
                 0.674 
                 0.362 
                 85 
                 80 
                 71 
                 56 
                 −8 
                 1.26E−5 
                 7.51E−5 
                 &gt;1.00E−4 
               
               
                   
               
             
          
         
       
     
         [0110]    While the invention has been described in terms of what is presently considered to be the most practical and preferred embodiments, it is to be understood that the invention needs not be limited to the disclosed embodiments. On the contrary, it is intended to cover various modifications and similar arrangements included within the spirit and scope of the appended claims which are to be accorded with the broadest interpretation so as to encompass all such modifications and similar structures. 
       CITATIONS 
       [0000]    
       
         1. Bestilny, L. J.; Brown, C. B.; Miura, Y.; Robertson, L. D.; Riabowol, K. T. Selective inhibition of telomerase activity during terminal differentiation of immortal cell lines.  Cancer Res.  1996, 56, 3796-802. 
         2. Bodnar, A. G.; Ouellette, M.; Frolkis, M.; Holt, S. E.; Chiu, C. P.; Morin, G. B.; Harley, C. B.; Shay, J. W.; Lichtsteiner, S.; Wright, W. E. Extension of life-span by introduction of telomerase into normal human cells.  Science.  1998, 279, 349-52. 
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