Synthesis, in silico study and cytotoxic evaluation of new benzimidazole derivatives as potential aromatase inhibitors.

AIMS: A new series of benzimidazole derivatives (4a-4p) was designed, synthesized, and evaluated as potential aromatase inhibitors with anticancer activity.

MATERIALS AND

METHODS

The anticancer effects of the compounds were evaluated using the MCF-7 cell line. Derivatives that showed activity were subjected to an aromatase inhibition assay. Molecular docking, molecular dynamics simulations, and in silico ADMET profiling were performed for the selected compounds.

RESULTS

Among the series, para-substituted derivatives 4d (Cl), 4h (OC2H5), and 4k (F) exhibited potent antiproliferative activity with low‑micromolar IC50 values (2.40-2.64 µM), surpassing cisplatin, while maintaining favorable selectivity profiles.

CONCLUSIONS

This experimental and computational study identifies 4d as a promising lead for further development as a non-steroidal aromatase inhibitor for breast cancer therapy.