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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th-mahidol.127002018-05-03T15:37:16Z Methotrexate is highly potent against pyrimethamine-resistant Plasmodium vivax Mallika Imwong Bruce Russell Rossarin Suwanarusk Alexis Nzila Mara L. Leimanis Kanlaya Sriprawat Supaporn Kaewpongsri Aung Pyae Phyo Georges Snounou Francois Nosten Laurent Renia Mahidol University Shoklo Malaria Research Unit Agency for Science, Technology and Research, Singapore Kenya Medical Research Institute Hopital Pitie Salpetriere Universite Pierre et Marie Curie Centre for Clinical Vaccinology and Tropical Medicine Medicine 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. © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. 2018-05-03T08:37:16Z 2018-05-03T08:37:16Z 2011-01-15 Article Journal of Infectious Diseases. Vol.203, No.2 (2011), 207-210 10.1093/infdis/jiq024 00221899 2-s2.0-79851491750 https://repository.li.mahidol.ac.th/handle/123456789/12700 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=79851491750&origin=inward |
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Medicine Mallika Imwong Bruce Russell Rossarin Suwanarusk Alexis Nzila Mara L. Leimanis Kanlaya Sriprawat Supaporn Kaewpongsri Aung Pyae Phyo Georges Snounou Francois Nosten Laurent Renia Methotrexate is highly potent against pyrimethamine-resistant Plasmodium vivax |
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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. © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. |
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Mahidol University |
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Mahidol University Mallika Imwong Bruce Russell Rossarin Suwanarusk Alexis Nzila Mara L. Leimanis Kanlaya Sriprawat Supaporn Kaewpongsri Aung Pyae Phyo Georges Snounou Francois Nosten Laurent Renia |
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Article |
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Mallika Imwong Bruce Russell Rossarin Suwanarusk Alexis Nzila Mara L. Leimanis Kanlaya Sriprawat Supaporn Kaewpongsri Aung Pyae Phyo Georges Snounou Francois Nosten Laurent Renia |
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Mallika Imwong |
title |
Methotrexate is highly potent against pyrimethamine-resistant Plasmodium vivax |
title_short |
Methotrexate is highly potent against pyrimethamine-resistant Plasmodium vivax |
title_full |
Methotrexate is highly potent against pyrimethamine-resistant Plasmodium vivax |
title_fullStr |
Methotrexate is highly potent against pyrimethamine-resistant Plasmodium vivax |
title_full_unstemmed |
Methotrexate is highly potent against pyrimethamine-resistant Plasmodium vivax |
title_sort |
methotrexate is highly potent against pyrimethamine-resistant plasmodium vivax |
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2018 |
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https://repository.li.mahidol.ac.th/handle/123456789/12700 |
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1763488517870059520 |