High-throughput screening affords novel and selective trypanothione reductase inhibitors with anti-trypanosomal activity

被引：40

作者：

Martyn, Derek C.

Jones, Deuan C.

Fairlamb, Alan H.

Clardy, Jon ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA

[2] Univ Dundee, Div Biol Chem & Mol Biochem, Dundee, Scotland

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 05期

基金：

英国惠康基金;

关键词：

trypanothione reductase; high-throughput screening; trypanosomiasis;

D O I：

10.1016/j.bmcl.2006.12.016

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Trypanothione reductase (TR), an enzyme that buffers oxidative stress in trypanosomatid parasites, was screened against commercial libraries containing approximately 134,500 compounds. After secondary screening, four chemotypes were identified as screening positives with selectivity for TR over human glutathione reductase. Thirteen compounds from these four chernotypes were purchased, and their in vitro activity against TR and Trypanosoma brucei is described. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：1280 / 1283

页数：4

共 8 条

[1] SUBSTRATE INTERACTIONS BETWEEN TRYPANOTHIONE REDUCTASE AND N(1)-GLUTATHIONYLSPERMIDINE DISULFIDE AT 0.28-NM RESOLUTION [J].