Document Detail

Insights into the role of heme in the mechanism of action of antimalarials.
MedLine Citation:
PMID:  23043646     Owner:  NLM     Status:  MEDLINE    
By using cell fractionation and measurement of Fe(III)heme-pyridine, the antimalarial chloroquine (CQ) has been shown to cause a dose-dependent decrease in hemozoin and concomitant increase in toxic free heme in cultured Plasmodium falciparum that is directly correlated with parasite survival. Transmission electron microscopy techniques have further shown that heme is redistributed from the parasite digestive vacuole to the cytoplasm and that CQ disrupts hemozoin crystal growth, resulting in mosaic boundaries in the crystals formed in the parasite. Extension of the cell fractionation study to other drugs has shown that artesunate, amodiaquine, lumefantrine, mefloquine, and quinine, all clinically important antimalarials, also inhibit hemozoin formation in the parasite cell, while the antifolate pyrimethamine and its combination with sulfadoxine do not. This study finally provides direct evidence in support of the hemozoin inhibition hypothesis for the mechanism of action of CQ and shows that other quinoline and related antimalarials inhibit cellular hemozoin formation.
Jill M Combrinck; Tebogo E Mabotha; Kanyile K Ncokazi; Melvin A Ambele; Dale Taylor; Peter J Smith; Heinrich C Hoppe; Timothy J Egan
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Publication Detail:
Type:  Letter; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-10-11
Journal Detail:
Title:  ACS chemical biology     Volume:  8     ISSN:  1554-8937     ISO Abbreviation:  ACS Chem. Biol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-18     Completed Date:  2013-07-02     Revised Date:  2014-01-24    
Medline Journal Info:
Nlm Unique ID:  101282906     Medline TA:  ACS Chem Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  133-7     Citation Subset:  IM    
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MeSH Terms
Antimalarials / pharmacology*
Chloroquine / pharmacology
Dose-Response Relationship, Drug
Heme / physiology*
Microscopy, Electron, Transmission
Plasmodium falciparum / drug effects*
Trophozoites / drug effects*
Grant Support
Reg. No./Substance:
0/Antimalarials; 42VZT0U6YR/Heme; 886U3H6UFF/Chloroquine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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