The synthesis and inhibitory activity of dethiotrypanothione and analogues against trypanothione reductase

被引：14

作者：

Czechowicz, Josephine A. ^{[1
]}

Wilhelm, April K. ^{[1
]}

Spalding, Maroya D. ^{[1
]}

Larson, Anna M. ^{[1
]}

Engel, Linnea K. ^{[1
]}

Alberg, David G. ^{[1
]}

机构：

[1] Carleton Coll, Dept Chem, Northfield, MN 55057 USA

来源：

JOURNAL OF ORGANIC CHEMISTRY | 2007年 / 72卷 / 10期

关键词：

D O I：

10.1021/jo062597s

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Trypanothione reductase (TR) catalyzes the NADPH-dependent reduction of trypanothione disulfide (1). TR plays a central role in the trypanosomatid parasite's defense against oxidative stress and has emerged as a promising target for antitrypanosomal drugs. We describe the synthesis and activity of dethiotrypanothione and analogues (2-4) as inhibitors of Trypanosoma cruzi TR. The syntheses of these macrocycles feature ring-closing olefin metathesis (RCM) reactions catalyzed by ruthenium catalyst 17. Derivative 4 is our most potent inhibitor with a K-i = 16 mu M.

引用

页码：3689 / 3693

页数：5

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