Synthesis of chiral thiosemicarbazone derivatives, determination of cytotoxic activities and modeling studies

Analysis of the structure and activity relationship of pharmaceutical active ingredients revealed that single isomers are selective so they are more effective than racemic mixtures. For this reason, in this study; expect to the anticancer activity of both of chiral thiosemicarbazone derivatives were synthesized. In first step, (R)-(+)-α-methylbenzylamine ve (S)-(-)-α-methylbenzylamine were converted to their corresponding isothiocyanates in the presence of thiophosgene in basic environment. In second step, that isothiocyanates were reacted by hydrazine hydrate to obtain thiosemicarbazide derivatives. In final step, the thiosemicarbazide derivatives were treated with appropriate 4-substituebenzaldehydes to gain chiral thiosemicarbazone derivatives. The chemical structures of all new compounds were characterized by elemental analysis (CHNS), UV-Vis, IR, 1H NMR, 13C NMR, HETCOR and mass spectroscopic techniques. The original chiral thiosemicarbazone derivatives were evaluated in vitro cytotoxic activity against sindaxel on A549, MCF-7, HeLa ve HGC-27 cell lines. Especially, compound 17b exhibited the most potent activity (IC50 4.6 μM) against HGC-27 cell lines. Conformational models of the compound 17b was investigated by HipHop method.