Dual inhibition of cell cycle progression and apoptotic resistance in breast cancer by novel benzimidazole-based therapeutics

Abstract

Breast cancer remains a leading cause of cancer-related mortality among women worldwide, underscoring the urgent need for more effective and targeted therapeutic strategies. Due to their diverse biological activities and structural flexibility, Benzimidazole derivatives have emerged as promising anticancer candidates. This study focuses on the development and chemical preparation of novel benzimidazole-based analogs, followed by an evaluation of their growth-inhibitory effects on MCF-7 and MDA-MB-231 human breast cancer cell lines. Among the synthesized molecules, compound 8a exhibited the most potent and selective anti-proliferative effect, with significantly lower IC50 values in cancer cells compared to normal cells. Flow cytometric analysis revealed that 8a induced apoptosis and caused an arrest in the cell division process during the G2/M transition phase. In silico interaction analysis further indicated a strong binding affinity of compound 8a to key cell cycle and apoptosis-regulating proteins, particularly Cyclin E, CDK2, Bcl-2, and Bcl-xL. These findings indicate that compound 8a exerts a dual mechanism of action by modulating both proliferative and survival pathways, highlighting its potential as a promising lead candidate for anticancer drug development.