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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Insights into the role of heme in the mechanism of action of antimalarials
ACS Chemical Biology, Volume 8, No. 1, Year 2013
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Description
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. © 2012 American Chemical Society.
Authors & Co-Authors
Combrinck, Jill M.
South Africa, Cape Town
University of Cape Town
Mabotha, Tebogo E.
South Africa, Cape Town
University of Cape Town
Ncokazi, Kanyile
South Africa, Cape Town
University of Cape Town
Ambele, Melvin Anyasi
South Africa, Cape Town
University of Cape Town
Taylor, Dale
South Africa, Cape Town
University of Cape Town
Smith, Peter John
South Africa, Cape Town
University of Cape Town
Hoppe, Heinrich C.
South Africa, Cape Town
University of Cape Town
Egan, Timothy John
South Africa, Cape Town
University of Cape Town
Statistics
Citations: 194
Authors: 8
Affiliations: 1
Identifiers
Doi:
10.1021/cb300454t
ISSN:
15548929
e-ISSN:
15548937
Research Areas
Environmental