Malaria-Infected Mice Are Cured by a Single Low Dose of a New Silylamide Trioxane Plus Mefloquine

Lauren E Woodard; Bryan T Mott; Vandana Singhal; Nirbhay Kumar; Theresa A Shapiro; Gary H Posner

doi:10.3390/ph2030228

Malaria-Infected Mice Are Cured by a Single Low Dose of a New Silylamide Trioxane Plus Mefloquine

Pharmaceuticals (Basel). 2009 Dec 21;2(3):228-235. doi: 10.3390/ph2030228.

Authors

Lauren E Woodard¹, Bryan T Mott², Vandana Singhal³, Nirbhay Kumar⁴, Theresa A Shapiro^{5

6}, Gary H Posner^{7

8}

Affiliations

¹ Department of Chemistry, School of Arts and Sciences, The Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218-2685, MD, USA. lwoodar1@jhu.edu.
² Department of Chemistry, School of Arts and Sciences, The Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218-2685, MD, USA. bmott2@jhu.edu.
³ Department of Molecular Microbiology and Immunology, Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD Baltimore, MD 21205, USA. vsinghal@jhsph.edu.
⁴ Department of Molecular Microbiology and Immunology, Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD Baltimore, MD 21205, USA. nkumar@jhsph.edu.
⁵ Department of Molecular Microbiology and Immunology, Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD Baltimore, MD 21205, USA. tshapiro@jhmi.edu.
⁶ Division of Clinical Pharmacology, Department of Medicine, School of Medicine, The Johns Hopkins University, Baltimore, MD 21205, USA. tshapiro@jhmi.edu.
⁷ Department of Chemistry, School of Arts and Sciences, The Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218-2685, MD, USA. ghp@jhu.edu.
⁸ Department of Molecular Microbiology and Immunology, Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD Baltimore, MD 21205, USA. ghp@jhu.edu.

Abstract

Three thermally and hydrolytically stable silylamide trioxanes have been prepared from the natural trioxane artemisinin in only five simple chemical steps and in at least 56% overall yield. Two of these new chemical entities completely cured malariainfected mice at a single oral dose of only 8 mg/kg combined with 24 mg/kg of mefloquine hydrochloride. The high efficacy of this ACT chemotherapy is considerably better than the efficacy using the popular trioxane drug artemether plus mefloquine hydrochloride.

Keywords: antimalarial monomers and dimmers; silylamide trioxanes; single dose oral cure.

Abstract

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