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Plasmodium berghei: Efficacy of 5-fluoroorotate in combination with commonly used antimalarial drugs in a mouse model

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dc.contributor.authorMuregi, Francis W.
dc.contributor.authorKano, Shigeyuki
dc.contributor.authorKino, Hideto
dc.contributor.authorIshih, Akira
dc.date.accessioned2024-07-25T10:00:09Z
dc.date.available2024-07-25T10:00:09Z
dc.date.issued2009-04
dc.description.abstractResistance to antimalarial antifolates necessitates a search for new antimetabolites targeting other enzymes of the folate metabolic pathway. In this study, 5-fluoroorotate (FOA), reported to be an inhibitor of thymidylate synthase, was assayed against Plasmodium berghei NK 65 in mice, with(out) an oral uridine supplement. FOA (2.5 and 5.0 mg/kg bw.) was tested alone, or in a double and triple combination with a fixed oral dose of 1.25 and 2.5 mg/kg of pyrimethamine (PYR); 1.0 and 2.0 mg/kg of dapsone (DAP); 1.0 and 2.0 mg/kg of artesunate (ART). FOA achieved high suppression which ranged from 95.7% to aparasitaemic, activity that was dose-dependent. At the highest dosages used, FOA–PYR and FOA–DAP–ART combinations were synergistic with 100% cure rate, while FOA–PYR–ART was antagonistic. Drugs in a synergistic combination may exert less resistance selection pressure, thus FOA–PYR and FOA–DAP–ART warrant further evaluation with an ultimate object of possible clinical use against drug-resistant malaria.
dc.identifier.citationFrancis W. Muregi, Shigeyuki Kano, Hideto Kino, Akira Ishih, Plasmodium berghei: Efficacy of 5-fluoroorotate in combination with commonly used antimalarial drugs in a mouse model, Experimental Parasitology, Volume 121, Issue 4, 2009, Pages 376-380, ISSN 0014-4894, https://doi.org/10.1016/j.exppara.2009.01.009. (https://www.sciencedirect.com/science/article/pii/S0014489409000101)
dc.identifier.urihttps://doi.org/10.1016/j.exppara.2009.01.009
dc.identifier.urihttps://erepository.mku.ac.ke/handle/123456789/6142
dc.language.isoen
dc.publisherExperimental Parasitology
dc.subjectPlasmodium falciparum
dc.subjectthe parasite
dc.titlePlasmodium berghei: Efficacy of 5-fluoroorotate in combination with commonly used antimalarial drugs in a mouse model
dc.typeArticle
dspace.entity.typePublication
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