Diarylmethyloxime and hydrazone derivatives with 5-indolyl moieties as potent inhibitors of tubulin polymerization

被引：46

作者：

Alvarez, Concepcion ^{[1
]}

Alvarez, Raquel ^{[1
]}

Corchete, Purificacion ^{[2
]}

Lopez, Jose Luis ^{[1
]}

Perez-Melero, Concepcion ^{[1
]}

Pelaez, Rafael ^{[1
]}

Medarde, Manuel ^{[1
]}

机构：

[1] Univ Salamanca, Fac Farm, Dept Quim Farmaceut, E-37007 Salamanca, Spain

[2] Univ Salamanca, Fac Farm, Dept Fisiol Vegetal, E-37007 Salamanca, Spain

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2008年 / 16卷 / 11期

关键词：

phenstatin; indole; tubulin; combretastatin; cytotoxicity; antitumour; oxime; hydrazone; hydrazide;

D O I：

10.1016/j.bmc.2008.04.054

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：

We describe the synthesis and biological evaluation of a series of diarylmethyloxime and diarylmethylhydrazone analogues that contain an indole ring and different modi. cations on the nitrogen of the bridge. Several compounds showed potent tubulin polymerization inhibitory action as well as cytotoxic activity against cancer cell lines. The N-methyl-5-indolyl substituted analogues are more potent than ethyl substituted ones. The most potent inhibitors of tubulin polymerization are the diarylketones and the diaryloximes. The cytotoxicity against several cancer cell lines is lower for the oximes than for the ketones. Other substitutions on the imine nitrogen greatly reduce the tubulin inhibitory and/or cytotoxic potencies. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：5952 / 5961

页数：10

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