Synthesis, antiproliferative activity, and in silico insights of new 3-benzoylamino-benzo[b]thiophene derivatives

Abstract

A new series of 3-benzoylamino-5-imidazol-5-yl-benzo[b]thiophenes and the parent amino derivatives were synthesized and screened as antitumor agents. All tested compounds showed concentration-dependent antiproliferative activity profile against HeLa cell line, exhibiting GI50 values in the low micromolar range. The most active compounds were tested in cell cycle perturbation experiments. A rapid accumulation of cells in the G2/M phase, with a concomitant reduction of cells in both the S and G0/G1 phases, was observed, suggesting that cell exposure to selected derivatives produces mitotic failure. To rationalize the biological results, the 3-benzoylamino-benzo[b]thiophenes were analyzed through the in silico VLAK protocol. Compounds presenting the 3,4,5-trimethoxy-benzoyl moiety were in silico classified as potential antimitotic agents or topoisomerase II inhibitors, in good agreement with the biological studies.

Keywords: 3-Benzoylamino-5-imidazol-4-yl-benzo[b]thiophenes; Antitumor agents; G2/M phase; HeLa cell line; Mechanism of action; VLAK protocol.