Curcumin analog cytotoxicity against breast cancer cells: exploitation of a redox-dependent mechanism

被引：46

作者：

Sun, Aiming ^{[1
]}

Lu, Yang J. ^{[2
]}

Hu, Haipeng ^{[1
]}

Shoji, Mamoru ^{[2
]}

Liotta, Dennis C. ^{[1
]}

Snyder, James P. ^{[2
]}

机构：

[1] Emory Univ, Dept Chem, Atlanta, GA 30322 USA

[2] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 23期

基金：

美国国家卫生研究院;

关键词：

Curcumin analogs; Glutathione; Anti-cancer; Pro-drug; NF-KAPPA-B; PEPTIDE-SYNTHESIS; KINASE; GLUTATHIONE; AGENTS; CYSTEINE; ACIDS; SUPPRESSION; ANTICANCER; ACTIVATION;

D O I：

10.1016/j.bmcl.2009.10.023

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of novel curcumin analogs, symmetrical dienones, were previously shown to possess cytotoxic, anti-angiogenic and anti-tumor activities. Analogs 1 (EF24) and 2 (EF31) share the dienone scaffold and serve as Michael acceptors. We propose that the anti-cancer effects of 1 and 2 are mediated in part by redox-mediated induction of apoptosis. In order to support this concept, 1 and 2 were treated with L-glutathione (GSH) and cysteine-containing dipeptides under mild conditions to form colorless water-soluble adducts, which were identified by LC/MS. Comparison of the cytotoxic action of 1, 2 and the corresponding conjugates, 1-(GSH)(2) and 2-(GSH)(2), illustrated that the two classes of compounds exhibit essentially identical cell killing capabilities. Compared with the yellow, somewhat light sensitive and nearly water insoluble compounds 1 and 2, the glutathione conjugates represent a promising new series of stable and soluble anti-tumor pro-drugs. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：6627 / 6631

页数：5