Methotrexate Is Highly Potent Against Pyrimethamine-Resistant Plasmodium vivax

Resistance of vivax malaria to treatment with antifolates, such as pyrimethamine (Pyr), is spreading as mutations in the dihydrofolatereductase (dhfr) genes are selected and disseminated. We tested the antitumor drug methotrexate (MTX), a potent competitive inhibitor of dhfr, against 11 Plasmodium v...

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Detalles Bibliográficos
Autores principales: Imwong, Mallika, Russell, Bruce, Suwanarusk, Rossarin, Nzila, Alexis, Leimanis, Mara L., Sriprawat, Kanlaya, Kaewpongsri, Supaporn, Phyo, Aung Pyae, Snounou, Georges, Nosten, Francois, Renia, Laurent
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2011
Materias:
Major Articles and Brief Reports
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3071051/
https://www.ncbi.nlm.nih.gov/pubmed/21288820
http://dx.doi.org/10.1093/infdis/jiq024
Descripción
Sumario:Resistance of vivax malaria to treatment with antifolates, such as pyrimethamine (Pyr), is spreading as mutations in the dihydrofolatereductase (dhfr) genes are selected and disseminated. We tested the antitumor drug methotrexate (MTX), a potent competitive inhibitor of dhfr, against 11 Plasmodium vivax isolates ex vivo, 10 of which had multiple dhfr mutations associated with Pyr resistance. Despite high-grade resistance to Pyr (median 50% inhibitory concentration [IC(50)](,) 13,345 nM), these parasites were all highly susceptible to MTX (median IC(50,) 2.6 nM). Given its potency against Pyr-resistant P. vivax, the antimalarial potential of MTX deserves further investigation.

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