pinecone/core-2020-05-10-deduplication huggingface dataset:
Reversal of P-Glycoprotein-Mediated Multidrug Resistance by Terpenoids from Maytenus Species

Preprint. Versión definitiva publicada con el título "Terpenoids from Maytenus Species and Assessment of Their Reversal Activity against a Multidrug-Resistant Leishmania tropica Line" DOI: 10.1002/cbdv.201000356The phytochemical analysis of the root bark extracts of the Chilean Maytenus, M. chubutensis, and M. magellanica (Celastraceae), led to the isolation of one phenolic nortriterpene, 1, and one diterpene with a nor-ent-kaurene skeleton, 2. In addition, four known compounds were isolated, among which compound 3 has been isolated for the first time from a natural source. Their structures were elucidated by spectroscopic methods, including 1D- and 2D-NMR (COSY, ROESY, HSQC, and HMBC) experiments, comparison with data reported in the literature, and chemical correlations. The isolated compounds were assayed for their reversal activity against a multidrug-resistant Leishmania tropica line, overexpressing a P-glycoprotein related transporter. Compound 1 showed moderate multidrug-resistance reversal activity. Copyright © 2011 Verlag Helvetica Chimica Acta AG, Zürich
Secondary metabolite profile in induced tetraploids of wild Solanum commersonii Dun.

The main aim of this work was to study the leaf secondary metabolite profiles of artificially induced tetraploids (2n1⁄44x1⁄448) of Solanum commersonii, a diploid (2n1⁄42x1⁄424) wild potato species. The tetraploid genotypes of S. commersonii were produced by oryzalin treatment. Both HPLC-UV and LC/ MS analyses revealed that there were no qualitative differences in the metabolite profiles between the diploid S. commersonii and its tetraploids. By contrast, the results showed that the phenylpropanoid content was generally significantly higher in the tetraploids than in the diploid S. commersonii. Concerning the glycoalkaloids (GAs), the results provided evidence that the content of minor GAs (solanidenediol triose, solanidadienol lycotetraose, and solanidenol lycotetraose) was higher in tetraploids than in the diploid progenitor, while the content of major GAs (dehydrodemissine and dehydrocommersonine) was significantly higher in diploid S. commersonii than in its tetraploid genotypes. The results are discussed from the practical perspective of potato biodiversity enhancement
Synthesis and acid-Base properties of an imidazole-containing nucleotide analog, 1-(2'-Deoxy-B-D-ribofuranosyl)imidazole 5'-monophosphate (dImMP2-)

Deletion of the substituted pyrimidine ring in purine-2'-deoxynucleoside 5'-monophosphates leads to the artificial nucleotide analog dImMP(2-). This analog can be incorporated into DNA to yield, upon addition of Ag+ ions, a molecular wire. Here, we measured the acidity constants of H-2(dImMP)(+/-) having one proton at N(3) and one at the PO32- group by potentiometric pH titrations in aqueous solution. The micro acidity constants show that N(3) is somewhat more basic than PO32- and, consequently, the (H center dot dImMP)(-) tautomer with the proton at N(3) dominates to ca. 75%. The calculated micro acidity constants are confirmed by P-31- and H-1-NMR chemical shifts. The assembled data allow many quantitative comparisons, e.g., the N(3)-protonated and thus positively charged imidazole residue facilitates deprotonation of the P(O)(2)(OH)- group by 0.3 pK units. Information on the intrinsic site basicities also allows predictions about metal-ion binding; e.g., Mg2+ and Mn2+ will primarily coordinate to the phosphate group, whereas Ni2+ and Cu2+ will preferably bind to N(3). Macrochelate formation for these metal ions is also predicted. The micro acidity constant for N(3)H+ deprotonation in the (H center dot dImMP center dot H)(+/-) species (pk(a) 6.46) and the Mn+-binding properties are of relevance for understanding the behavior of dImMP units present in DNA hairpins and metalated duplexes
Unusually high-affinity Mg2+ binding at the AU-rich sequence within the antiterminator hairpin of a Mg2+ riboswitch

Mg2+-Responsive riboswitches represent a fascinating example of bifunctional RNAs that sense Mg2+ ions with high selectivity and autonomously regulate the expression of Mg2+-transporter proteins. The mechanism of the mgtA riboswitch is scarcely understood, and a detailed structural analysis is called for to study how this RNA can selectively recognize Mg2+ and respond by switching between two alternative stem loop structures. In this work, we investigated the structure and Mg2+-binding properties of the lower part of the antiterminator loop C from the mgtA riboswitch of Yersinia enterocolitica by solution NMR and report a discrete Mg2+-binding site embedded in the AU-rich sequence. At the position of Mg2+ binding, the helical axis exhibits a distinct kink accompanied by a widening of the major groove, which accommodates the Mg2+-binding pocket. An unusually large overlap between two adenine residues on the opposite strands suggests that the bending may be sequence-induced by strong stacking interactions, enabling Mg2+ to bind at this so-far not described metal-ion binding site
Front-Loading Natural-Product-Screening Libraries for log P: Background, Development, and Implementation

In the period from January 1981 to December 2010, 1068 small-molecule new chemical entities (NCEs) were introduced, of which ca. 34% are either a natural product or a close analogue. While this metric reflects the impact natural products have played in delivering new chemical starting points (leads) for the pharmaceutical industry, it does not capture the decline this approach has suffered over the last 20 years as the high-throughput screening (HTS) of pure compound libraries has become more popular. An impediment to natural-product drug discovery in the HTS paradigm is the lack of a clear strategy that enables front-loading of an extract or fraction's chemical constituents so that they are compliant with lead- and drug-like chemical space. To address this imbalance, an approach based on lipophilicity, as measured by clog P has been developed that, together with advances being made in isolation and structural elucidation, can afford natural product leads in timelines compatible with pure compound screening.Full Tex
Contribution to a Taxonomic Revision of the Sicilian Helichrysum Taxa by PCA Analysis of Their Essential-Oil Compositions

The chemical profile of the essential oils in ten populations of the genus Helichrysum Mill. (Asteraceae), collected in the loci classici of the nomenclatural types of the taxa endemic to Sicily, were analyzed. Our results confirm that the analysis of secondary metabolites can be used to fingerprint wild populations of Helichrysum, the chemical profiles being coherent with the systematic arrangement of the investigated populations in three main clusters, referring to the aggregates of H. stoechas, H. rupestre, and H. italicum, all belonging to the section Stoechadina. The correct nomenclatural designation of the investigated populations is discussed and the following two new combinations are proposed: Helichrysum preslianum subsp. compactum (Guss.) Maggio, Bruno, Guarino, Senatore & Ilardi and Helichrysum panormitanum subsp. latifolium Maggio, Bruno, Guarino, Senatore & Ilardi
Lasiolactols A and B Produced by the Grapevine Fungal Pathogen Lasiodiplodia mediterranea

A strain of Lasiodiplodia mediterranea, a fungus associated with grapevine decline in Sicily, produced several metabolites in liquid medium. Two new dimeric c-lactols, lasiolactols A and B (1and 2), were characterized as (2S*,3S*,4R*,5R*,20S*,30S*,40R*,50R*)-  and  (2R*,3S*,4R,5R*,20R*,30S*,40R*,50R*)-5-(4-hydroxymethyl-3,5-dimethyl-tetrahydro-furan-2-yloxy)-2,4-dimethyl-tetrahydro-furan-3-yl]-methanols by IR, 1D- and 2D-NMR, and HR-ESI-MS. Other fourmetabolites were identified as botryosphaeriodiplodin, (5R\ud
)-5-hydroxylasiodiplodin, (–)-(1R,2R)-jasmonic acid, and (–)-(3S,4R,5R)-4-hydroxymethyl-3,5-dimethyldihydro-2-furanone (3-6, resp.). The absolute configuration (R) at hydroxylatedsecondary C-atom C(7) was also established for compound 3. The compounds 1–3,5,and 6, tested for their phytotoxic activities to grapevine cv. Inzolia leaves at different concentrations (0.125, 0.25, 0.5, and 1 mg/ml) were phytotoxic and compound 5\ud
showed the highest toxicity. All metabolites did not show in vitro antifungal activity against four plant pathogens
Bioactive secondary metabolites from Schizogyne sericea (Asteraceae) endemic to Canary Islands

Schizogyne sericea (Asteraceae) is a species endemic to the Canary Islands and traditionally employed as analgesic, astringent, anti-inflammatory and vulnerary. A comprehensive phytochemical investigation was conducted on the flowering aerial parts by analyzing both essential oil constituents and polar compounds. The essential oil was dominated by p-cymene, with the noteworthy occurrence of β-pinene and thymol esters. From the ethanolic extract eight compounds were isolated and structurally elucidated. Essential oil, polar fractions and isolates (2), (4) and (5) were separately in vitro assayed for antiproliferative activity on human tumor cell lines (A375, MDA-MB 231, HCT 116) by MTT assay, for antioxidant potential by DPPH, ABTS and FRAP assays, and for antimicrobial activity by the agar disc diffusion method. Results revealed that essential oil and compounds 1 and 2 exert a strong inhibition on tumor cells, in some cases higher than that of cisplatin. Fractions containing thymol derivatives (1 and 2) and compounds 4 and 5 displayed antioxidant activity comparable to that of Trolox, making S. sericea extract an interesting natural product with potential applications as preservative or in the treatment of diseases in which oxidative stress plays an important role
Detection and toxicity evaluation of pyrrolizidine alkaloids in medicinal plants Gynura bicolor and Gynura divaricata collected from different Chinese locations

Two edible plants in Southeast Asia, Gynura bicolor and G.divaricata, are not only known to be nutritive but also useful as medicinal herbs. Previous phytochemical investigation of Gynura species showed the presence of hepatotoxic pyrrolizidine alkaloids (PAs), indicating the toxic risk of using these two plants. The present study was designed to analyze the distribution of PA components and tried to evaluate the preliminary toxicity of these two Gynura species. Eight samples of G.bicolor and G.divaricata from five different Chinese locations were collected and their specific PAs were qualitatively characterized by applying an UPLC/MS/MS spectrometry method. Using a pre-column derivatization HPLC method, the total retronecine ester-type PAs in their alkaloids extracts were quantitatively estimated as well. Finally, their genotoxicity was investigated with an effective high-throughput screening method referred to as Vitotox test and their potential cytotoxicity was tested on HepG2 cells. It was found that different types of PAs were widely present in Gynura species collected from south of China. Among them, no significant genotoxic effects were detected with serial concentrations through the present invitro assay. However, the cytotoxicity assay of Gynura plants collected from Jiangsu displayed weak activity at the concentration of 100mg/ml. It is important to note that this research validates in part the indication that the use of Gynura species requires caution
Terpenes as Useful Markers in Differentiation of Natural Populations of Relict Pines Pinus heldreichii , P . nigra , and P . peuce

Comparative analysis of terpene diversity and differentiation of relict pines Pinus heldreichii, P. nigra, and P. peuce from the central Balkans was performed at the population level. Multivariate statistical analyses showed that the composition of needle terpenes reflects clear divergence among the pine species from different subgenera: P. peuce (subgenus Strobus) vs. P. nigra and P. heldreichii (subgenus Pinus). In addition, despite the described morphological similarities and the fact that P. nigra and P. heldreichii may spontaneously hybridize, our results indicated differentiation of their populations naturally growing in the same area. In accordance with recently proposed concept of 'flavonic evolution' in the genus Pinus, we assumed that the terpene profile of soft pine P. peuce, defined by high amounts of six monoterpenes, is more basal than those of hard pines P. nigra and P. heldreichii, which were characterized by high content levels of mainly sesquiterpenes. In order to establish precise positions of P. heldreichii, P. nigra and P. peuce within the taxonomic and phylogenetic tree, as well as develop suitable conservation strategies and future breeding efforts, it is necessary to perform additional morphological, biochemical, and genetic studies
Chemical Profiling and Assessment of Antineurodegenerative and Antioxidant Properties of Veronica teucrium L. and Veronica jacquinii Baumg.

Neuroprotective potential of V. teucrium and V. jacquinii methanol extracts was analyzed. Chemical analysis of investigated extracts showed the presence of phenolic acid derivatives, flavonoids and one secoiridoid. The detected flavonoids derived from flavones (luteolin and isoscutellarein in V. jacquinii; apigenin, isoscutellarein and luteolin in V. teucrium) and flavonol (quercetin in V. jacquinii). Acteoside was the dominant compound in V. jacquinii, while plantamajoside and isoscutellarein 7-O-(6â€´-O-acetyl)-ß-allosyl (1â€´?2â€´)-ß-glucoside were the major phenolics in V. teucrium. Additionally, the antineurodegenerative activity was tested at concentrations of 25, 50, and 100 µg/ml using acetylcholinesterase (AChE) and tyrosinase (TYR) assays. The inhibition of both enzymes was achieved with the investigated extracts, ranging from 22.78 to 35.40% for AChE and from 9.57 to 16.38% for TYR. There was no statistical difference between the activities of the analyzed extracts. Our data indicate that V. teucrium and V. jacquinii may have beneficial effects against Alzheimer's and Parkinson's disease.The authors are grateful to Fundac ~ao para a Ci^encia e
a Tecnologia (FCT, Portugal) for financial support to
CIMO (strategic project PEst-OE/AGR/UI0690/2011). J.
C. M. Barreira and M. I. Dias thank FCT, POPH-QREN,
and FSE for their grants (SFRH/BPD/72802/2010 and
SFRH/BD/84485/2012, respectively). The GIP-USAL is
financially supported by the Spanish Government
through the project AGL2015-64522-C2-2-R. The
authors are also grateful to the Serbian Ministry of Education,
Science and Technological Development for
financial support (Grant Numbers 173032, 173029, and
46013).info:eu-repo/semantics/publishedVersio
[2.2](4,7)Isobenzofuranophanes - Synthesis, Characterisation and Reactivity

The isomeric Diels-Alder adducts 3, obtained by cycloaddition of tetraphenylcyclopentadienone to the 4,5:12,13-bis-(oxanorbornadieno)[2.2]paracyclophanes syn,syn- and anti,-syn-2[Note ][The stereochemical descriptors syn and anti refer to the orientation of the oxygen bridge in the oxabicyclo[2.2.1]heptadiene subunits with respect to the [2.2]paracyclophaneskeleton.], yield the unstable isobenzofuranophane 4 by consecutive extrusion of carbon monoxide and tetraphenylbenzene when heated to 180°C. The molecular ion of 4 was observed in the EI mass spectrum. The stable tetraphenyl-substituted analogue 10 was synthesized independently from the previously unknown 4,5,12,13-tetrabenzoyl[2.2]paracyclophane (9). UV/Vis as well as fluorescence spectra and an X-ray crystal structure analysis of 9 are reported
Highly alkylated cyclohexanes. X-Ray crystal structures, force-field calculations, and conformations of cis/trans-1,4-disubstituted cyclohexane isomers

The structures of mesylated cis- and trans-tetramethylshisool cis- 2 and trans-2 have been elucidated by single-crystal X-ray techniques. In cis-2 the isopropenyl group adopts an axial position in the crystal, and the structural data obtained are in good agreement with those from force-field calculations. In trans-2 the two rotamers arising from rotation of the isopropenyl group were assigned by NOE measurements. Comparison of the spectroscopic data with those of other tetramethyllimonene derivatives showed that these can be classified into compounds with preferred equatorial and preferred axial position of the isopropenyl group.
Koordinationschemie -gebundener Cyclopentadienyl-Chalkogeno-Ether

Coordination Chemistry of rr-Bonded Cyclopentadienyl Chalcogeno Ethers, I. - Chelate Complexes of Pentakis(methylthio)cymantrene with Metal Carbonyls 
[C5(SMe)5]Mn(CO)3 (1) reacts with W(CO)5(THF), Mo(CO)4(C7H8), Cr(CO)3(NCMe)3, and Re(CO)4(-C3H5)/HBF4 to yield the monochelate complexes [[C5(SMe)5]Mn(C0)3][M(CO)4] (M = W: 2; M = Mo: 3) and the dichelate complexes [[C5(SMe)5]Mn(CO)3][M(C0)4]2 (M = W: 4; M = Cr: 5; M = Re BFF4 : 6). The reaction with Mo(CO)3(p-xylene) in THF leads via unstable intermediates, which contain coordinated THF, to a mixture of 3 and [[C5(SMe)5]Mn(CO)3][Mo(CO)4]2 (7). The structures of 3 and 4 in the crystal have been determined by X-ray diffraction methods.
Kohlenwasserstoffverbrückte Komplexe, XXV

Hydrocarbon-Bridged Complexes, XXV. - C-C Coupling of Anionic Tricarbonyl Manganese Complexes of Cyclic Polyenes with Cationic Tropylium Metal Compounds; Preparation and Structure of (OC)3Mn(-5:6-C7H8-C7H7)M(CO)3, (OC)3Mn(-5:6-C8H10-C7H7)M(CO)3, and (OC)3Mn(-5:5-C8H8-C7H7)M(CO)3 (M = Cr, Mo, W)[Note ] 
The addition of the anionic complexes [(4-C7H8)Mn(CO)3]-, [(4-C8H10)Mn(CO)3]- and [(4-C8H8)Mn(CO)3]- to the cations [(7-C7H7)M(CO)3]+ (M = Cr, Mo, W) gives the hydrocarbon-bridged complexes (OC)3Mn(-5:6-C7H8-C7H7)M(CO)3, (OC)3Mn(-5:6-C8H10-C7H7)M(CO)3, and (OC)3Mn(-5:6-C8H8-C7H7)M(CO)3 (M = Cr, Mo, W). The structures of 4b and 6a have been determined by X-ray diffraction.
Koordinationschemie perhalogenierter Cyclopentadiene und Alkine, X

Coordination Chemistry of Perhalogenated Cyclopentadienes and Alkynes, X[1]. - Synthesis and Molecular Structure of a Cyclopentadienyl-1,3-dithiol  Complex, [C5Cl3(SH)2]Mn(CO)3 
The reaction of [C5Cl4Li]Mn(CO)3 with elemental sulfur leads to [C5Cl4SLi]Mn(CO)3 (1), which is easily oxidized by air to the disulfide (OC)3Mn[C5Cl4S-SCl4C5]Mn(CO)3 (2). Addition of one equivalent of BuLi, followed by an excess of S8 produces the dithiolate [C5Cl3(SLi)2]Mn(CO)3 (3), which yields the dithiol [C5Cl3(SH)2]Mn(CO)3 (5) upon hydrolysis. The molecular structures of 2 and 5 have been determined by X-ray diffraction.
Synthesis and Diels-Alder Reactions of 1,2-Dimethylene- and 1,2,9,10-Tetramethylene-[2.2]paracyclophane: New Routes to Bridge-Anellated[2.2]Paracyclophanedienes

The title compounds 8 and 1 have been synthesized in three steps each from 1,2-dibromo[2.2]paracyclophan-1-ene (2) and 1,2,9,10-tetrabromo[2.2]paracyclophane-1,9-diene (4), respectively. Copper-mediated coupling of vinyl bromides 2 and 4 with methyl- and phenylmagnesium bromide gives substituted [2.2]paracyclophanes 3-CH3, 3-Ph, 5-CH3, and 5-Ph in good yields. The high reactivity of the [2.2]paracyclophane-1,2-dimethylene moieties in 8 and 1 in Diels-Alder reactions has been verified in cycloadditions with p-benzoquinone to give 10 and 13 and with naphthalene 1,4-endoxide to yield 12
Double-Layered 1,4-Distyrylbenzene Chromophores - Synthesis, UV and Fluorescence Spectra

The reaction of [2.2]paracyclophane (1) with liquid bromine affords a 1:1 mixture of only two isomeric products, the pseudo-para 2 and pseudo-ortho tetrabromide 3. The structure of the pseudo-para isomer 2 has been determined by X-ray structure analysis. Fourfold palladium-catalyzed coupling with styrenes and with methyl acrylate converts 2 and 3 into double-layered derivatives as e.g. 6a, 7a, and 7b, respectively. The molecular structure of 7a has been established by X-ray structure analysis. The UV and fluorescence spectra of a variety of substituted products are reported and compared with those of the parent chromophors 2,5-dimethyl-1,4-distyrylbenzene (16) and 2,5-diethyl-1,4-bis(phenylethynyl)benzene (17), respectively
Koordinationschemie Perhalogenierter Cyclopentadine und Alkine, XV

Coordination Chemistry of Perhalogenated Cyclopentadienes and Alkynes, XV[1]. - Systematic Generation of Fivefold Ring-Silylated Cyclopentadienyl Manganese Complexes from [C5Br5]Mn(CO)3. Molecular Structure of [C5Br3(SiMe3)2]Mn(CO)3 
[C5Br5]Mn(CO)3 reacts in a sequence of alternate bromine-lithium exchange reactions and electrophilic silylations by SiMe3Cl or SiMe3OSO2CF3 to give [C5Br5-n(SiMe3)n]Mn(CO)3, where n = 1 (1), 2 (2), or 3 (3). A crystal structure determination of 2 shows the two silyl substituents in the relative 1,3-orientation. Addition of one or two equivalents of BuLi and SiMe2HCl to a solution of 3 yields [C5Br2-n(SiMe3)3-(SiMe2H)n]Mn(CO)3 with n = 1 (4) and 2 (5), respectively. If 1 is treated twice with 2 eq. of BuLi and then 2 eq. of SiMe2HCl, a further pentasilylated compound, [C5(SiMe3)(SiMe2H)4]-Mn(CO)3 (6), is obtained. In situ chlorination of [C5(SiMe2H)5]Mn(CO)3 or 6 with PdCl2, followed by addition of MeMgCl, yields after chromatography an inseparable mixture of [C5(SiMe3)4X]Mn(CO)3 compounds, where X = H (7a), SiMe2H (7b), and SiMe3 (7c).
A Stepwise [4 + 3] Cycloaddition Reaction of the 1,3-Diphenyl-2-azaallyl Anion

The 1,3-diphenyl-2-azaallyl anion (1) undergoes [3 + 2] cycloaddition reactions with the s-cis-fixed 1,3-dienes 8-11. In contrast, 1,1,2,2,3,3-hexamethyl-4,5-bis(methylene)cyclopentane (7) reacts with 1 to give the [4 + 3] cycloadduct 13 and the linear 1,4-addition product 14. This reaction is four orders of magnitude slower than the corresponding reaction of 1 with 1,2-bis(methylene)cyclopentane (8), which exclusively yields [3 + 2] cycloadducts. A change of mechanism - concerted cycloaddition of 8 and stepwise cycloaddition of 7 - is suggested, but not unequivocally proven. It is concluded that reactions of 1 with ordinary dienes cannot profit from concertedness by more than 5 kcal · mol-1.
Metallkomplexe mit biologisch wichtigen Liganden, LXVIII

The trischelate complexes of the dianion of aspartic acid and -methylaspartic acid (5-C5Me5)
(R = H, Me) form adducts with alkali iodides MI (M = Li, Na, K). The polymeric structure of (5-C5Me5)Co(L-asp.-2H+)KI (1c) was determined by X-ray diffraction. In the crystal of 1c the potassium ions are surrounded by five oxygen atoms of the carboxylate groups whereby two oxygen atoms form bridges between two K+ ions. Similarly, trischelate complexes 4 and 5 have been obtained from (5-C5Me5)Co(CO)I2 and 2,3-diaminopropionic, 2,4-diaminobutyric acid, and asparagine, respectively.
Comparison of the Nucleophilicities of Alkynes and Alkenes. Quantitative Determination of the Nucleophilicities of Alkynes toward Carbenium Ions

Relative reactivities of alkenes and alkynes toward diarylmethyl cations have been determined by direct rate measurements and by competition experiments in dichloromethane. At -70°C alkynes are found to be one to two orders of magnitude less reactive than analogously substituted alkenes (e.g. phenylacetylene/styrene), but the reactivity difference reduces strongly as the temperature is raised. The stereochemistry of the vinyl chlorides produced by addition of benzhydryl chlorides to alkynes is characterized.
Fully Chlorinated N-Silyl Amides of Titanium and Tungsten

The reaction of hexachlorodisilazanyllithium (Cl3Si)2NLi (1), with TiCl4 leads selectively to the novel fully chlorinated amides (Cl3Si)2NTiCl3 (2) or [(Cl3Si)2N]2 TiCl2 (3), respectively, depending on the molar ratio of the starting materials. The analogous reaction of 1 with WCl6 yielded the amide imide Cl3SiNW(Cl3)N(SiCl3)2 (5) by elimination of SiCl4. The relative amounts of the starting materials had no effect on the formation of 5. 14/15N- and 29Si-NMR data on the starting materials and products show significantly different effects, when compared with those of analogous N-trimethylsilyl derivatives, due to the lower energy of the electrons in the NSi and NM ß bonds. The crystal structure of 5 (triclinic, space group P1) was determined by X-ray structure analysis.