Design, synthesis, and biological evaluation of 6-aryl-3-(3,4,5-trimethoxyphenyl)imidazo[1,2-a]pyridine derivatives as novel tubulin inhibitors with potent anticancer efficacy.

Authors

Wen Xu, Yujing Zhang, Qianqian Xu, Haibo Zhao, Liya Cui, Chao Wang

Published in

Journal of enzyme inhibition and medicinal chemistry. Volume 41. Issue 1. Pages 2686919. Epub Jun 17, 2026.

Abstract

Tubulin, the fundamental component of microtubules, remains a critical target in anticancer therapy. The development of small-molecule tubulin polymerization inhibitors continues to drive the discovery of novel chemotherapeutic agents. Through systematic analysis of known tubulin inhibitors and in silico binding pocket models, a focused series of 6-aryl-3-(3,4,5-trimethoxyphenyl)imidazo[1,2-a]pyridine derivatives was rationally designed and synthesized. Compound 8o exhibited superior antiproliferative potency, with IC₅。 values of 0.050-0.078 µM against HeLa, HCT116, and MCF-7 cancer cell lines. Mechanistic investigations confirmed that 8o effectively inhibits tubulin polymerization, disrupts the microtubule cytoskeleton, induces G₂/M phase arrest, and triggers apoptosis. Preliminary physicochemical assessment indicated that 8o adheres to Lipinski's rule of five, supporting favorable drug-likeness. Collectively, these findings identify 8o as a potent, drug-like colchicine-site tubulin inhibitor with compelling anticancer efficacy, meriting further investigation as a promising lead compound.

PMID:
42306850
Bibliographic data and abstract were imported from PubMed on 17 Jun 2026.

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