Synthesis and biological activity studies of new hydrazone derivatives

In order to develop selective and potent anticancer agents, in this study, 13 new hydrazone derivatives bearing a pyrimidine ring were synthesized. The structures of the obtained compounds were elucidated by IR, 1H NMR, 13C NMR and mass spectroscopy. The cytotoxic effects of all compounds on 5RP7 H-ras oncogene transformed rat embryonic fibroblast and L929 mouse embryonic fibroblast cell lines were investigated using MTT assay. According to in vitro activity tests, N'-benzylidene-2-[(4-(4-chlorophenyl)pyrimidin-2-yl)thio]acetohydrazide (3a), N'-(4-(pyrrolidin-1-yl)benzylidene)-2-[(4-(4-chlorophenyl)pyrimidin-2-yl)thio]acetohydrazide (3d), N'-benzylidene-2-[(4-(4-methoxyphenyl)pyrimidin-2-yl)thio]acetohydrazide (3g), N'-(4-(pyrrolidin-1-yl)benzylidene)-2-[(4-(4-methoxyphenyl)pyrimidin-2-yl)thio]acetohydrazide (3j) were found to be effective on 5RP7 cells (with IC50 values <0.97, <0.97, 1.13±0.06 and <0.97 µg/mL, respectively) when compared with cisplatin (IC50= 1.87±0.15 µg/mL). Besides, the apoptotic effects of these active compounds on 5RP7 cell line were evaluated using flow cytometry. It was determined that these four compounds induced apoptosis in 5RP7 cell line.