Design, synthesis of new hydrazone derivatives and studies on their anticancer activity

In this study, ten new hydrazone derivatives (3a-j) were synthesized and their structures were confirmed using spectroscopic methods. The cytotoxic activities of all compounds on A549 human lung adenocarcinoma and L929 mouse embryonic fibroblast cells were determined by MTT assay. N'-(4-Dimethylaminobenzylidene)-2-[(5-chlorobenzoxazol-2-yl)thio]acetohydrazide (3a), N'-[4-(piperidin-1-yl)benzylidene]-2-[(5-chlorobenzoxazol-2-yl)thio]acetohydrazide (3e), N'-[4-(4-methylpiperazin-1-yl)benzylidene]-2-[(5-chlorobenzoxazol-2-yl)thio]acetohydrazide (3g) and N'-[4-(1H-imidazol-1-yl)benzylidene]-2-[(5-chlorobenzoxazol-2-yl)thio]acetohydrazide (3i) showed selective anticancer effect on A549 cell line. The effects of these compounds on apoptosis and Akt were also evaluated. Compounds 3a and 3g caused apoptosis induction in A549 cells stronger than cisplatin. However, these two compounds did not show any significant inhibitory effect on Akt. Compounds 3e and 3i showed Akt inhibitory effects in A549 cells. As a result of in vitro studies, it was determined that compounds 3e and 3i showed their anticancer effects on A549 cell line through Akt inhibition. However, it is understood that compounds 3a and 3g exert their cytotoxic and apoptotic effects on A549 cells via different pathway(s).