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Research Papers

Design, synthesis and biological evaluation of novel diarylpyridine derivatives as tubulin polymerisation inhibitors

, , , , , , , , , & show all
Pages 2755-2764 | Received 07 Jun 2022, Accepted 23 Sep 2022, Published online: 05 Oct 2022
 

Abstract

A set of novel diarylpyridines as anti-tubulin agents were designed, synthesised using a rigid pyridine as a linker to fix the cis-orientation of ring-A and ring-B. All of the target compounds were evaluated for their in vitro antiproliferative activities. Among them, 10t showed remarkable antiproliferative activities against three cancer cell lines (HeLa, MCF-7 and SGC-7901) in sub-micromolar concentrations. Consistent with its potent antiproliferative activity, 10t also displayed potent anti-tubulin activity. Cellular mechanism investigation elucidated 10t disrupted the cellular microtubule structure, arrested cell cycle at G2/M phase and induces apoptosis. Molecular modelling studies showed that 10t could bind to the colchicine binding site on microtubules. These results provide motivation and further guidance for the development of new CA-4 analogues.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This work was supported by grants from the Natural Science Foundation of Shandong [ZR2021QH156], the Medical and Health Science and Technology Development Plan Project of Shandong [202113051140] and the Youth Innovation Team Talent Introduction Program of Shandong Province [20190164].