Design, synthesis, and biological evaluation of a new class of benzo[b]furan derivatives as antiproliferative agents, with in silico predicted antitubulin activity

Abstract

A new series of 3-benzoylamino-5-(1H-imidazol-4-yl)methylaminobenzo[b]furans were synthesized and screened as antitumor agents. As a general trend, tested compounds showed concentration-dependent antiproliferative activity against HeLa and MCF-7 cancer cell lines, exhibiting GI₅₀ values in the low micromolar range. In most cases, insertion of a methyl substituent on the imidazole moiety improved the antiproliferative activity. Therefore, methyl-imidazolyl-benzo[b]furans compounds were tested in cell cycle perturbation experiments, producing cell cycle arrest with proapoptotic effects. Their core similarity to known colchicine binding site binders led us to further study the structure features as antitubulin agents by in silico protocols.

Keywords: 3-benzoylamino-5-(1H-imidazol-4-yl)methylaminobenzo[b]furans; G2/M phase; HeLa and MCF-7 cell lines; VLAK protocol; antitubulin agents; antitumor agents; colchicine binding site; induced fit docking studies.