Cytotoxic effects of Mannich bases via induction of caspase-3 pathway on human oral squamous cell carcinoma

Abstract

In the anticancer drug research, there is a need for the synthesis of compounds with selectivecytotoxicity compared to the anticancer drugs in the market. The current study aimed to determine thecytotoxicities of the bis Mannich bases 1-9 towards human oral squamous cell carcinoma (OSCC).Mannich bases showed promising cytotoxicity in low micromolar in the range of 1.7-27 µM against OSCCcell lines. The compounds 5 with the highest potency selectivity expression (PSE) value (318.1) and 7with the highest tumor selectivity (TS) values (TS1:11.2, TS2:15.8) showed promising selectivecytotoxicity towards cancer cell lines. Furthemore, Western blot analysis showed that the representativecompound 7 induced the activation of caspase-3 in HSC-2 cells. These results may suggest that theapoptotic pathway may be one of the possible mechanisms of the action and the lead compound 7 can besubjected to the further bioassays and molecular design.