Synthesis and biological evaluation of novel heterocyclic derivatives of combretastatin A-4

被引：18

作者：

Thi Thanh Binh Nguyen ^{[1
]}

Lomberget, Thierry ^{[1
]}

Ngoc Chau Tran ^{[1
]}

Colomb, Evelyne ^{[2
]}

Nachtergaele, Lore ^{[2
]}

Thoret, Sylviane ^{[3
]}

Dubois, Joelle ^{[3
]}

Guillaume, Joren ^{[1
]}

Abdayem, Rawad ^{[2
]}

Haftek, Marek ^{[2
]}

Barret, Roland ^{[1
]}

机构：

[1] Univ Lyon 1, Fac Pharm, EA Biomol Canc & Chimioresistances 4446, ISPB,SFR Sante Lyon E,CNRS,UMS3453,INSERM,US7, F-69373 Lyon 08, France

[2] Univ Lyon 1, Fac Med & Pharm, EA 4169, F-69373 Lyon 08, France

[3] CNRS, Inst Chim Subst Nat, UPR 2301, F-91198 Gif Sur Yvette, France

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 23期

关键词：

Combretastatin A-4; Antimitotic; Benzoheterocycles; Inhibitors of tubulin assembly; Keratinocyte; ANTITUMOR-ACTIVITY; ANTINEOPLASTIC AGENTS; ANALOGS; POTENT; TUBULIN; BINDING; CIS; CYTOTOXICITY; DEPROTECTION; GROWTH;

D O I：

10.1016/j.bmcl.2012.09.047

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel series of combretastatin A-4 heterocyclic analogues was prepared by replacement of the B ring with indole, benzofurane or benzothiophene, attached at the C2 position. These compounds were evaluated for their abilities to inhibit tubulin assembly: derivative cis 3b, having a benzothiophene, showed an activity similar to those of colchicine or deoxypodophyllotoxine. The antiproliferative and antimitotic properties of cis 3b against keratinocyte cancer cell lines were also evaluated and the intracellular organization of microtubules in the cells after treatment with both stereoisomers of 3b was also determined, using confocal microscopy. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：7227 / 7231

页数：5

共 51 条

[1] In vitro metabolism study of combretastatin A-4 in rat and human liver Microsomes [J].