Inhibitors and promoters of tubulin polymerization: Synthesis and biological evaluation of chalcones and related dienones as potential anticancer agents

被引：91

作者：

Dyrager, Christine ^{[1
]}

Wickstrom, Malin ^{[2
]}

Friden-Saxin, Maria ^{[1
]}

Friberg, Annika ^{[1
]}

Dahlen, Kristian ^{[1
]}

Wallen, Erik A. A. ^{[1
,3
]}

Gullbo, Joachim ^{[2
]}

Grotli, Morten ^{[1
]}

Luthman, Kristina ^{[1
]}

机构：

[1] Univ Gothenburg, Dept Chem, SE-41296 Gothenburg, Sweden

[2] Univ Uppsala Hosp, Dept Med Sci, Div Clin Pharmacol, SE-75185 Uppsala, Sweden

[3] Univ Helsinki, Fac Pharm, Div Pharmaceut Chem, FI-00014 Helsinki, Finland

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2011年 / 19卷 / 08期

基金：

瑞典研究理事会; 芬兰科学院;

关键词：

Chalcones; Cytotoxicity; Tubulin polymerization; Molecular modeling; PHARMACOPHORE; CYTOTOXICITY; MICROCULTURE; MICROTUBULES; COLCHICINE; BINDING;

D O I：

10.1016/j.bmc.2011.03.005

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

A series of dihalogenated chalcones and structurally related dienones were synthesized and evaluated for their antiproliferative activity in 10 different cancer cell lines and for their effect on microtubule assembly. All compounds showed cytotoxic activity, with IC50 values in the 5-280 mu M range depending on the chalcone structure and the cell line. Five of the compounds were found to be tubulin polymerization inhibitors. In contrast, one of the compounds was found to stabilize tubulin to the same extent as the anticancer drug docetaxel. Molecular modeling suggested that the tubulin inhibitors bind to the colchicine binding site of beta-tubulin while the novel tubulin stabilization agent seems to interact with the paclitaxel binding site. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：2659 / 2665

页数：7

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