Discovery and molecular modeling of novel 1-indolyl acetate-5-Nitroimidazole targeting tubulin polymerization as antiproliferative agents

被引：27

作者：

Duan, Yong-Tao ^{[1
]}

Sang, Ya-Li ^{[1
]}

Makawana, Jigar A. ^{[1
]}

Teraiya, Shashikant B. ^{[1
]}

Yao, Yong-Fang ^{[1
]}

Tang, Dan-Jie ^{[1
]}

Tao, Xiang-Xiang ^{[1
]}

Zhu, Hai-Liang ^{[1
]}

机构：

[1] Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Jiangsu, Peoples R China

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2014年 / 85卷

关键词：

Indolyl acetate; Nitroimidazole; Tubulin; Docking; COMBRETASTATIN A-4 ANALOGS; COLCHICINE-SITE INHIBITORS; ANTIMITOTIC AGENTS; NATURAL-PRODUCTS; BINDING; INDIBULIN;

D O I：

10.1016/j.ejmech.2014.07.082

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 18 novel 1-indolyl acetate-5-nitroimidazole 3a-3r were designed, synthesized, and evaluated for their in vitro biological activities as potential tubulin polymerization inhibitors. Among these compounds, 3p displayed strong antitumor activity with IC50 of 2.00, 1.05, 0.87 mu M against A549, Hela and U251 respectively, and also showed the most potent PLK1 inhibitory activity with IC50 of 2.4 mu M. Molecular docking studies within the colchicine binding site of tubulin were in good agreement with the tubulin polymerization inhibitory data and confirmed the importance of the configuration of the synthesized 1-indolyl acetate-5-nitroimidazolefor potential tubulin polymerization inhibitors. (C) 2014 Elsevier Masson SAS. All rights reserved.

引用

页码：341 / 351

页数：11

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