Imidazolone-amide bridges and their effects on tubulin polymerization in cis-locked vinylogous combretastatin-A4 analogues: Synthesis and biological evaluation

被引：34

作者：

Li, Yao-Wu ^{[2
]}

Liu, Jia ^{[1
]}

Liu, Na ^{[1
]}

Shi, Duo ^{[1
]}

Zhou, Xiao-Tian ^{[1
]}

Lv, Jia-Guo ^{[1
]}

Zhu, Ju ^{[1
]}

Zheng, Can-Hui ^{[1
]}

Zhou, You-Jun ^{[1
]}

机构：

[1] Second Mil Med Univ, Sch Pharm, Shanghai 200433, Peoples R China

[2] Air Force Gen Hosp, Beijing 100036, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2011年 / 19卷 / 11期

基金：

中国国家自然科学基金;

关键词：

Imidazolone-amide; Tubulin polymerization inhibitor; Antitumor agent; ANTICANCER AGENTS; A-4; ANALOGS; DERIVATIVES; THIOPHENES; INHIBITORS; CHALCONES; A4;

D O I：

10.1016/j.bmc.2011.03.068

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A series of novel combretastatin-A4 analogues in which the cis-olefinic bridge is replaced by an imidazolone-amide were synthesized, and their cytotoxicity and tubulin-polymerization inhibitory activities were evaluated. These compounds appear to be potential tubulin-polymerization inhibitors. Compounds 10, 9b and 9c, bearing 3'-NH2-4'-OCH3, 4'-CH3 and 3'-CH3-substituted 1-phenyl B-ring, confer optimal bioactivity. The binding modes of these compounds to tubulin were obtained by molecular docking, which can explain the compounds' structure-activity relationship. The studies presented here provide a new structural type for the development of novel antitumor agents. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：3579 / 3584

页数：6

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