N-Phenyl-N′-(2-chloroethyl)urea analogues of combretastatin A-4:: Is the N-phenyl-N′-(2-chloroethyl)urea pharmacophore mimicking the trimethoxy phenyl moiety?

被引：30

作者：

Fortin, Sebastien

Moreau, Emmanuel ^{[1
]}

Lacroix, Jacques

Teulade, Jean-Claude

Patenaude, Alexandre

C-Gaudreault, Rene

机构：

[1] Univ Laval, Hop St Francois Assise, CHUQ, Ctr Rech,Unite Biotechnol & Bioingn, Laval, PQ G1L 3L5, Canada

[2] Univ Clermont 1, UFR Pharm, Lab Chim Organ, F-63001 Clermont Ferrand, France

[3] INSERM, U484, F-63001 Clermont Ferrand, France

[4] Ctr Jean Perrin, F-63001 Clermont Ferrand, France

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 07期

关键词：

D O I：

10.1016/j.bmcl.2007.01.023

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of novel N-phe.rlyl-N'-(2-chloroethyl)urea derivatives potentially mimicking the structure of combretastatin A-4 were synthesized and tested for their cell growth inhibition and their binding to the colchicine-binding site of beta-tubulin. Compounds 2a, 3a, and 3b were found to inhibit cell growth at the micromolar level on four human tumor cell lines. Flow cytometric analysis indicates that the new compounds act as antimitotics and arrest the cell cycle in G(2)/M phase. Covalent binding of 2a, 3a, and 3b to the colchicine-binding site of beta-tubulin was confirmed also using SDS-PAGE and competition assays. (c) 2007 Elsevier Ltd. All rights reserved.

引用

页码：2000 / 2004

页数：5

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