# Anticancer Efficacy of Antibacterial Quinobenzothiazazines
## 3 Results and Discussion  
All recently described target alkoxyquinolinobenzothiazinium chlorides **4a-1**[53] were evaluated against human glioblastoma SNB-19, lung adenocarcinoma A549 and breast T47D cancer cell lines; i.e., cancer cells representing completely different cancers with different sensitivities were used. The abilities of compounds **4a-1** to inhibit the viability of human cancer cells were compared with those of cisplatin and doxorubicin and expressed as IC\({}_{50}\) values. Normal human dermal fibroblasts (NHDFs) were used as a control for the cytotoxic effect on human noncancer cells. All results are shown in Table 1.  
9-Propoxy derivative **4a** against SNB-19 and A549 cells, 9-allylovary derivative **4d** against A549 and T47D cells and 11-benzyl derivative **4l** against SNB-19 and T47D cells were the most active compounds. On the other hand, 11-propagyloxy (**4i**), 11-allylovy (**4f**) and 11-propoxy (**4c**) derivatives were the least active. These facts show the overall disadvantage of substitution at the C\({}_{(11)}\) position with a nonaromatic substituent. It should be noted that active derivatives did not exhibit cytotoxic effects up to 100 uM on NHDF cells. Only **4j**, **4i** and **4b** demonstrated cytotoxicity, with IC\({}_{50}\) values of 37.7, 47.5 and 65.5 uM, respectively, against NHDF cells. The results in Table 1 show that anticancer activity is influenced by the type/nature of substitution and the position of individual substituents. From the activity against SNB-19 cells, it can be observed that the presence of a multiple bond and the number of unsaturated bonds (up to the formation of an aromatic ring) shift the efficacy within the trio of positional isomers from position C\({}_{(9)}\) (compound **4a**) through C\({}_{(10)}\) (compounds **4e** and **4h**) to C\({}_{(11)}\) (compound **4l**). The initially inactive derivatives **4c,f,i** substituted atC\({}_{(11)}\) with an aliphatic chain turned into one of the most active compounds after benzyloxy substitution (compound **4l**). For activity against A544 cells, substitution at the C\({}_{(9)}\) position with propoxy and allyoxy (compounds **4a**, **4d**) appears to be the most favorable. All three benzyloxy-substituted positional isomers **4j**-**1** showed similar moderate activity. In the case of the T47D cell line, it can only be stated that derivatives substituted with a propoxy chain showed the worst activity; on the contrary, the presence of a chain with a multiple bond (allyoxy and propargyloxy) in position C\({}_{(9)}\)/C\({}_{(10)}\) and/or substitution with a benzyloxy moiety in position C\({}_{(11)}\) is advantageous. Thus, it can be inferred that substitutions of C\({}_{(9)}\) with propoxy or allyoxy and C\({}_{(11)}\) with benzyloxy moieties seem to be the most advantageous for anticancer activity. This finding is consistent with previously published results [52], where the most significant antiproliferative activity was associated with substitution at the C\({}_{(9)}\) position with a simple small substituent, such as -OCH\({}_{3}\), -F, -Cl or -Br. Unfortunately, this activity was against both cancer lines and noncancer NHDF cells [52]. High anticancer activity was also associated with substitution at the C\({}_{(9)}\) position with piperazine or the C\({}_{(10)}\) position with an \(N\)-pyrrolidinliethoxy chain. On the other hand, the substitution at the C\({}_{(9)}\) position of 5-methyl-12(\(H\))-quino[3,4-\(b\)][1,4]benzothizanium chloride with a phenyl ring caused a decrease in activity [51]. The published mechanisms of the antiproliferative effects of both derivatives substituted on the nitrogen atom of thiazine and similar derivatives substituted at the C\({}_{(9)}\) or C\({}_{(10)}\) positions of quino[3,4-\(b\)][1,4]benzothize indicate the binding of these compounds to cellular DNA [50,51].