Design, synthesis and biological evaluation of benz-fused five-membered heterocyclic compounds as tubulin polymerization inhibitors with anticancer activities.

A series of benz-fused five-membered heterocyclic compounds were designed and synthesized as novel tubulin inhibitors targeting the colchicine binding site. Among them, compound 4d displayed the highest antiproliferative activity against four cancer cell lines with an IC value of 4.9 μM in B16-F10 cells. Compound 4d effectively inhibited tubulin polymerization in vitro (IC of 13.1 μM). Further, 4d induced cell cycle arrest in G2/M phase. Finally, 4d inhibited the migration of cancer cells in a dose-dependent manner. In summary, these results suggest that compound 4d represents a new class of tubulin inhibitors deserving further investigation.