Antimalarial activities of ferroquine conjugates with either glutathione reductase inhibitors or glutathione depletors via a hydrolyzable amide linker

被引：46

作者：

Chavain, Natascha ^{[1
]}

Davioud-Charvet, Elisabeth ^{[2
,3
]}

Trivelli, Xavier ^{[4
]}

Mbeki, Linda ^{[1
]}

Rottmann, Matthias ^{[5
]}

Brun, Reto ^{[5
]}

Biot, Christophe ^{[1
]}

机构：

[1] Univ Lille 1, Unite Catalyse & Chim Solide, UMR 8181, CNRS,ENSCL, F-59652 Villeneuve Dascq, France

[2] Heidelberg Univ, Biochem Zentrum Heidelberg, D-69120 Heidelberg, Germany

[3] Univ Strasbourg, UMR 7509, Chim Bioorgan Lab, CNRS,ECPM, F-67087 Strasbourg 2, France

[4] Univ Lille 1, Unite Glycobiol Struct & Fonct, UMR 8576, CNRS, F-59655 Villeneuve Dascq, France

[5] Swiss Trop Inst, CH-4002 Basel, Switzerland

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2009年 / 17卷 / 23期

关键词：

Bioorganometallics; Dual drugs; Hemozoin; Glutathione reductase; Mechanism of action; PLASMODIUM-FALCIPARUM; IN-VITRO; DRUG-RESISTANCE; RODENT MALARIA; SULFADOXINE-PYRIMETHAMINE; ANTIPLASMODIAL ACTIVITY; CHLOROQUINE-RESISTANT; CRYSTAL-STRUCTURE; PLASMEPSIN-II; PRODRUG FORM;

D O I：

10.1016/j.bmc.2009.10.008

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Based on the prodrug concept as well as the combination of two different classes of antimalarial agents, we designed and synthesized two series of ferrocenic antimalarial dual molecules consisting of a ferroquine analogue conjugated with a glutathione reductase inhibitor (or a glutathione depletor) through a cleavable amide bond in order to target two essential pathways in the malarial parasites. The results showed no enhancement of the antimalarial activity of the dual molecules but evidenced a unique mode of action of ferroquine and ferrocenyl analogues distinct of those of chloroquine and nonferrocenic 4-aminoquinoline analogues. (c) 2009 Elsevier Ltd. All rights reserved.

引用

页码：8048 / 8059

页数：12

共 58 条

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