Synthesis, biological evaluation, and molecular modelling of new naphthalene-chalcone derivatives as potential anticancer agents on MCF-7 breast cancer cells by targeting tubulin colchicine binding site

Abstract

A series of naphthalene-chalcone derivatives (<b>3a-3t</b>) were prepared and evaluated as tubulin polymerisation inhibitor for the treatment of breast cancer. All compounds were evaluated for their antiproliferative activity against MCF-7 cell line. The most of compounds displayed potent antiproliferative activity. Among them, compound <b>3a</b> displayed the most potent antiproliferative activity with an IC₅₀ value of 1.42 ± 0.15 µM, as compared to cisplatin (IC₅₀ = 15.24 ± 1.27 µM). Additionally, the promising compound <b>3a</b> demonstrated relatively lower cytotoxicity on normal cell line (HEK293) compared to tumour cell line. Furthermore, compound <b>3a</b> was found to induce significant cell cycle arrest at the G₂/M phase and cell apoptosis. Compound <b>3a</b> displayed potent tubulin polymerisation inhibitory activity with an IC₅₀ value of 8.4 µM, which was slightly more active than the reference compound colchicine (IC₅₀ = 10.6 µM). Molecular docking analysis suggested that <b>3a</b> interact and bind at the colchicine binding site of the tubulin.