Insights into the Role of Heme in the Mechanism of Action of Antimalarials
Citations Over TimeTop 1% of 2012 papers
Abstract
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.
Related Papers
- → Mathematical modelling of malaria chemotherapy: combining artesunate and mefloquine(2002)23 cited
- → The neurological assessment in young children treated with artesunate monotherapy or artesunate-mefloquine combination therapy for uncomplicated Plasmodium falciparum malaria(2009)13 cited
- → Randomised trial of artesunate and mefloquine alone and in sequence for acute uncomplicated falciparum malaria(1992)159 cited
- [Comparison of sensitivity of artesunate-sensitive and artesunate-resistant Plasmodium falciparum to chloroquine and amodiaquine].(1999)