Antimalarial drugs inhibiting hemozoin (β-hematin) formation:: A mechanistic update

被引：133

作者：

Kumar, Sanjay ^{[1
]}

Guha, Mithu ^{[1
]}

Choubey, Vinay ^{[1
]}

Maity, Pallab ^{[1
]}

Bandyopadhyay, Uday ^{[1
]}

机构：

[1] Cent Drug Res Inst, Div Drug Traget Discovery & Dev, Lucknow 226001, Uttar Pradesh, India

来源：

LIFE SCIENCES | 2007年 / 80卷 / 09期

关键词：

heme toxicity; hemozoin formation; malaria; antimalarial drugs; PARASITE PLASMODIUM-FALCIPARUM; HISTIDINE-RICH PROTEINS; MALARIA PARASITE; IN-VITRO; HEME DETOXIFICATION; QUINOLINE ANTIMALARIALS; FERRIPROTOPORPHYRIN-IX; ANTIPLASMODIAL ACTIVITY; BISQUINOLINE ANTIMALARIALS; HEMOGLOBIN CATABOLISM;

D O I：

10.1016/j.lfs.2006.11.008

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Digestion of hemoglobin in the food vacuole of the malaria parasite produces very high quantities of redox active toxic free heme. Hemozoin (beta-hematin) formation is a unique process adopted by Plasmodium sp. to detoxify free heme. Hemozoin formation is a validated target for most of the well-known existing antimalarial drugs and considered to be a suitable target to develop new antimalarials. Here we discuss the possible mechanisms of free heme detoxification in the malaria parasite and the mechanistic details of compounds, which offer antimalarial activity by inhibiting hemozoin formation. The chemical nature of new antimalarial compounds showing antimalarial activity through the inhibition of hemozoin formation has also been incorporated, which may help to design future antimalarials with therapeutic potential against multi-drug resistant malaria. (c) 2006 Elsevier Inc. All rights reserved.

引用

页码：813 / 828

页数：16

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