Design and Evaluation of Novel Benzimidazolo-Triazole-Tetrazole Derivatives as Anticancer Agents Against MCF-7 Cells

Abstract

In this study, a novel series of benzimidazolo-1,2,4-triazole-tetrazole derivatives were synthesized in moderate to good yields. The structures of the synthesized compounds were confirmed using NMR, FTIR, MS, and elemental analysis. Given that cancer remains a leading cause of mortality worldwide, we utilized an in silico approach to evaluate the anticancer potential of these compounds through molecular docking studies. The results identified three derivatives as the most potent, demonstrating strong interactions with key active site residues of the target protein (–6.48 to –6.86 kcal/mol). Further in silico analyses, including ADMET profiling, revealed that these compounds exhibit favorable pharmacological properties, suggesting their potential as promising lead candidates for anticancer therapy. To validate the in silico findings, the most potent derivatives were tested against breast cancer (MCF-7) cells. Among these, one derivative exhibited the highest cytotoxicity, with an IC50 value of 0.29 µM, followed by others with IC50 values of 0.54 µM and 0.65 µM, compared to the reference drug 5-fluorouracil (IC50 = 0.11 µM). Additionally, one derivative demonstrated a high inhibitory percentage of 85.15%, while the others showed inhibition percentages of 72.57 and 65.38%, respectively. In comparison, 5-fluorouracil achieved an inhibitory percentage of 96.02%. These findings highlight the potential of benzimidazolo-1,2,4-triazole-tetrazole scaffolds as promising candidates for the development of novel anticancer agents.