3-aryl-4-(3,4,5-trimethoxyphenyl)pyridines inhibit tubulin polymerisation and act as anticancer agents

Abstract

A series of cis-restricted 3-aryl-4-(3,4,5-trimethoxyphenyl)pyridines as novel tubulin polymerisation inhibitors was designed based on molecular docking. Compound 9p, exhibited potent antiproliferative activity against HeLa, MCF-7, and A549 cell lines. Mechanism studies indicated that 9p potently inhibited tubulin polymerisation and disrupted the microtubule dynamics of tubulin in HeLa cells. Moreover, 9p could cause G2/M phase cell cycle arrest and apoptosis in HeLa cells. In addition, the prediction of physicochemical properties disclosed that 9p conformed well to the Lipinski’s rule of five. The initial results suggest that the 3-aryl-4-(3,4,5-trimethoxyphenyl)pyridines could serve as a promising scaffold for the development of novel anticancer drugs.

Keywords:

• Combretastatin A-4
• antiproliferative activity
• pyridine
• tubulin
• molecular docking

Author contributions

Chao Wang: methodology, validation, investigation, writingoriginal draft, writing-review & editing, funding acquisition. Yujing Zhang: methodology, validation, investigation. Shanbo Yang: synthesis of the compound. Lingyu Shi: investigation, visualisation. Yutao Xiu: validation, resources. Yudong Wu: conceptualisation, project administration. Hongfei Jiang: supervision, writing-review and editing.

Disclosure statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Additional information

Funding

This work was supported by grants from the National Natural Science Foundation of China [82303590], the Natural Science Foundation of Shandong [ZR2021QH156 and ZR2020QC081], the Natural Science Foundation of Qingdao [23–2-1–141-zyyd-jch], and the Medical and Health Science and Technology Development Plan Project of Shandong [202113051140].