Synthesis and biological activity of mustard derivatives of combretastatins

被引：28

作者：

Coggiola, B ^{[1
]}

Pagliai, F ^{[1
]}

Allegrone, G ^{[1
]}

Genazzani, AA ^{[1
]}

Tron, GC ^{[1
]}

机构：

[1] Univ Piemonte Orientale, DiSCAFF, I-28100 Novara, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 15期

关键词：

alkylating agents; antiproliferative activity; combretastatin A-4; chlorambucil; tubulin polymerization;

D O I：

10.1016/j.bmcl.2005.05.052

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of chimeric compounds bearing the combretastatin and the nitrogen mustard cores were synthesized. All the compounds were cytotoxic and inhibited tubulin polymerization. When combretastatin was joined to chlorambucil via an ester linkage, the resultant compound proved to be significantly more potent than the two compounds put together. When combretastatin was joined to nitrogen mustard via an ether linkage or when a true hybrid was synthesized, loss of potency was observed. Nonetheless, these latter compounds appeared to be more efficacious and surprisingly were able to inhibit tubulin depolymerization at high concentrations. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：3551 / 3554

页数：4

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