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.