New thiophene analogues of kenpaullone:: synthesis and biological evaluation in breast cancer cells

被引：83

作者：

Brault, L ^{[1
]}

Migianu, E ^{[1
]}

Néguesque, A ^{[1
]}

Battaglia, E ^{[1
]}

Bagrel, D ^{[1
]}

Kirsch, G ^{[1
]}

机构：

[1] Univ Metz, UFR SciFA, Lab Ingn Mol & Biochim Pharmacol, F-57070 Metz, France

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2005年 / 40卷 / 08期

关键词：

paullone analogues; cytotoxicity; cell cycle; apoptosis; breast cancer;

D O I：

10.1016/j.ejmech.2005.02.010

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Thieno analogues of kenpaullone have been synthesized using an established method. We investigated the effect of five structural analogues of kenpaullone on vincristine sensitive and resistant MCF7 (human mammary adenocarcinoma) cells. One analogue, 8-Bromo-6,11-dihydro-thermo-[3',2':2,3]azepino[4,5-b]indol-5(4H)-one (3a), showed an antiproliferative activity in the drug sensitive cell line that led to cell accumulation in G2/M phase. In addition, repression of cdk 1. a G2/M transition key regulator, as well as induction of p21 were observed at the mRNA level. Programmed cell death (apoptosis) was induced in early time treatments and was accompanied by p53 mRNA induction. The antiproliferative and proapoptotic properties of 3a make this CDK inhibitor an interesting candidate for further investigations. (c) 2005 Elsevier SAS. All rights reserved.

引用

页码：757 / 763

页数：7

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