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A single, low, oral dose of a 5-carbon-linked trioxane dimer orthoester plus mefloquine cures malaria-infected mice |
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| Authors: | Moon Deuk Kyu Tripathi Abhai Sullivan David Siegler Maxime A Parkin Sean Posner Gary H |
| Affiliation: | a Department of Chemistry, Johns Hopkins University, Baltimore, MD 21218, United States b W Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, United States c Malaria Research Institute, Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, United States d Department of Chemistry, University of Kentucky, Lexington, KY 40506, United States |
| Abstract: | Four 5-carbon-linked trioxane dimer orthoesters (6a-6d) have been prepared in 4 or 5 chemical steps from the natural trioxane artemisinin (1). When administered orally to malaria-infected mice using a single dose of only 6 mg/kg body weight along with 18 mg/kg of mefloquine hydrochloride, trioxane dimer orthoester sulfone 6d completely and safely cured the mice; after 30 days, the cured mice showed no detectable parasitemia, gained at least as much weight as the control mice (no infection), and behaved normally. |
| Keywords: | Antimalarial chemotherapy Trioxane dimer orthoesters Single oral dose ACT cure |
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