期刊
JOURNAL OF INFECTIOUS DISEASES
卷 203, 期 2, 页码 207-210出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiq024
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资金
- Agency for Science Technology and Research (A*STAR, Singapore)
- Novartis Institute for Tropical Diseases (Singapore)
- Wellcome Trust (United Kingdom)
- Wellcome Trust of Great Britain
- Wellcome Trust-Mahidol University
- Wellcome Trust [080867/Z/06/Z]
- Thailand Research Fund
- Commission on Higher Education
- Pfizer, United Kingdom
- EU Commission [018834]
- European and Developing Countries Clinical Trials Partnership
- Wellcome Trust [080867/Z/06/Z] Funding Source: Wellcome Trust
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 [IC50], 13,345 nM), these parasites were all highly susceptible to MTX (median IC50, 2.6 nM). Given its potency against Pyr-resistant P. vivax, the antimalarial potential of MTX deserves further investigation.
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