Azabenzimidazole-piperazine compounds as anticancer agents: Synthesis, biological evaluation, and molecular docking studies

Abstract

The cytotoxic activities of the newly synthesized azabenzimidazole–piperazine hybrid compounds were evaluated against three human cancer cell lines-HCT116 (colon), PC-3 (prostate), and MCF-7 (breast)-as well as the non-cancerous human embryonic kidney cell line HEK-293. Among all tested candidates, compounds 6d, 6k, and 6l demonstrated the most pronounced anticancer activities, exhibiting IC₅₀ values below 25 μM across all three cancer cell lines. Notably, compound 6l inhibited HCT116, PC-3, and MCF-7 cells with IC₅₀ values of 18.4 ± 0.7 μM, 15.2 ± 0.4 μM, and 14.4 ± 0.2 μM, respectively. Compound 6d showed even greater potency against MCF-7 cells (10.7 ± 0.6 μM) and exhibited comparable activity against HCT116 (14.0 ± 0.4 μM) and PC-3 (17.7 ± 1.5 μM) cells. Compound 6k also displayed significant cytotoxicity, with IC₅₀ values of 24.8 ± 1.6 μM for HCT116, 18.7 ± 0.8 μM for PC-3, and 20.2 ± 0.4 μM for MCF-7 cells. The integration of in silico molecular docking results with in vitro cytotoxicity data strongly suggests that the synthesized compounds-particularly 6d, 6k, and 6l-exert their anticancer effects through a multifaceted mechanism of action.