Novel bis-benzimidazole-triazole hybrids: anticancer study, in silico approaches, and mechanistic investigation

Aim Benzimidazole-triazole conjugates are very active hotspot for design and synthesis of promising anticancer agents. The target analogs showed potent and selective cytotoxicity over different cancer cell lines for breast and lung ones.Materials HepG-2, MCF-7, HCT-116, and A-549. Computational experiments were introduced for understanding their structure–activity relationships.Results 4–13 µg/mL compared to the reference drugs. Moreover, detailed mechanistic analyses showed potent Aurora-A Kinase expression for the most active analogs 7a and 7d exhibiting IC50; 3.5 and 5.3 over the control cells 8 ng/mL respectively. Additionally, based on their Aurora-A Kinase inhibitory activity, compound 7a was promising in apoptosis induction and cell cycle arrest. Molecular docking studies with Aurora-A Kinase revealed binding behaviors similar to the co-crystallized ligand sunitinib. Finally, this scaffold exhibits cytotoxic activity via apoptosis, enzyme downregulation, and suppression of cell division.