Design, Synthesis, and Biological Evaluation of New Benzimidazole‐1,2,4‐Triazole Derivatives as Potential Anticancer Agents

ABSTRACT New series of benzimidazole‐1,2,4‐triazole derivatives were designed, synthesized, and characterized using 1H‐NMR, 13C‐NMR, and HRMS. These compounds were evaluated for anticancer activity toward HTB‐9 bladder and HT‐29 colorectal cancer cell lines. Compounds 7h and 7ı were found to be the most active against HTB‐9 cell line, with IC50 6.27 and 6.44 μM, respectively, comparable to positive control cisplatin (IC50 = 11.40 μM). Additionally, in HT‐29 cell line, compounds 7a and 7ı exhibited the lowest IC50 values (20.37 and 22.71 μM, respectively), which was higher than those of cisplatin (19.79 μM). All active compounds induced apoptosis and caspase 3/7 activity and reduced the migration ability in both cell lines. Particularly, HT‐29 cells treated with compound 7ı exerted a higher apoptotic index than cisplatin‐treated cells. Furthermore, compounds 7h and 7ı led to G1 cell cycle arrest of HTB‐9, and compounds 7a and 7ı against HT‐29 induced S and G1 cell cycle arrest, respectively. In conclusion, the antiproliferative effect of active compounds is associated with the induction of apoptosis through caspase 3/7 activation and cell cycle arrest at different phases in HTB‐9 and HT‐29 cell lines. Compounds 7h and 7ı in HTB‐9 and compounds 7a and 7ı in HT‐29 cell line demonstrated most cytotoxic activity among all compounds. These compounds expectedly increased apoptosis, activated caspase 3/7, and inhibited migration in both cell lines compared to controls. As a remarkable result, a greater apoptotic index was observed in HT‐29 cells treated with compound 7ı than those of cisplatin‐treated cells. Compounds 7h and 7ı inhibited the G1 cell cycle in HTB‐9; however, compounds 7a and 7ı led to cell cycle arrest in different phases (S and G1) in HT‐29.