3-芳基-4-(3,4,5-三甲氧基苯基)吡啶抑制微管蛋白聚合，可作为抗癌剂。

IF 5.6 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2023-12-11 DOI:10.1080/14756366.2023.2286939

Chao Wang, Yujing Zhang, Shanbo Yang, Lingyu Shi, Yutao Xiu, Yudong Wu, Hongfei Jiang

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引用次数: 0

摘要

在分子对接的基础上设计了一系列顺式限制的 3-芳基-4-(3,4,5-三甲氧基苯基)吡啶作为新型管蛋白聚合抑制剂。化合物 9p 对 HeLa、MCF-7 和 A549 细胞系具有强效的抗增殖活性。机理研究表明，9p 能有效抑制 HeLa 细胞中的微管蛋白聚合，并破坏微管蛋白的微管动力学。此外，9p 还能导致 HeLa 细胞 G2/M 期细胞周期停滞和凋亡。此外，对理化性质的预测显示，9p 非常符合利宾斯基的 "5 "法则。初步结果表明，3-芳基-4-(3,4,5-三甲氧基苯基)吡啶可作为开发新型抗癌药物的支架。

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

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.

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来源期刊

Journal of Enzyme Inhibition and Medicinal Chemistry 医学-生化与分子生物学

CiteScore

10.30

自引率

10.70%

发文量

195

审稿时长

4-8 weeks

期刊介绍： Journal of Enzyme Inhibition and Medicinal Chemistry publishes open access research on enzyme inhibitors, inhibitory processes, and agonist/antagonist receptor interactions in the development of medicinal and anti-cancer agents. Journal of Enzyme Inhibition and Medicinal Chemistry aims to provide an international and interdisciplinary platform for the latest findings in enzyme inhibition research. The journal’s focus includes current developments in: Enzymology; Cell biology; Chemical biology; Microbiology; Physiology; Pharmacology leading to drug design; Molecular recognition processes; Distribution and metabolism of biologically active compounds.