Synthesis and cytotoxic evaluation of combretastatin A-4 analogues of benzo[b]furans

摘要

A series of benzo[b]furans was synthesized with modification at the 5-position of the benzene ring by introducing different aryl acetylenyl and acrylic acid moiety as combretastatin A-4 analogues. The compounds were evaluated by MTT assay for cytotoxic effects against lung cancer (A549), liver cancer (BEL-7404), colon cancer (SW620), and cervical cancer (HeLa) cell lines and the compounds were more sensitive to A549 and Hela cell lines. One compound exhibited the highest inhibition against A549 and Hela cells (IC50 = 0.18 and 0.14 mu M) and very close to that of CA-4 (IC50 = 0.16 and 0.12 mu M). This compound elicited cell-cycle arrest in the G(2)/M phase and significantly induced apoptosis in HeLa cells. Molecular docking studies indicated that it displayed hydrogen-bonding interactions with the amino acid residues Gln-11 and Tyr-224 would be a potential tululin inhibitor.