A single, low, oral dose of a 5-carbon-linked trioxane dimer orthoester plus mefloquine cures malaria-infected mice

Deuk Kyu Moon; Abhai Tripathi; David Sullivan; Maxime A. Siegler; Sean Parkin; Gary H. Posner

doi:10.1016/j.bmcl.2010.09.123

A single, low, oral dose of a 5-carbon-linked trioxane dimer orthoester plus mefloquine cures malaria-infected mice

Deuk Kyu Moon
, Abhai Tripathi
, David Sullivan
, Maxime A. Siegler
, Sean Parkin
, Gary H. Posner

Chemistry

Research output: Contribution to journal › Article › peer-review

23 Scopus citations

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.

Original language	English
Pages (from-to)	2773-2775
Number of pages	3
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	21
Issue number	9
DOIs	https://doi.org/10.1016/j.bmcl.2010.09.123
State	Published - May 1 2011

Bibliographical note

Funding Information:
We thank the NIH ( AI 34885 to G.H.P.), the Johns Hopkins Malaria Research Institute , and the Bloomberg Family Foundation for financial support (to G.H.P. and to D.S.).

Funding

We thank the NIH ( AI 34885 to G.H.P.), the Johns Hopkins Malaria Research Institute , and the Bloomberg Family Foundation for financial support (to G.H.P. and to D.S.).

Funders	Funder number
National Institutes of Health (NIH)
National Institute of Allergy and Infectious F32-AI286447 Cydney N. Johnson Diseases National Institute of Allergy and Infectious R01AI168214 Jason W. Rosch Diseases National Institute of Allergy and Infectious P30 Cydney N. Johnson Diseases National Institute of Allergy and Infectious R00-AI166116 Christopher D. Radka Diseases National Institute of Allergy and Infectious T32-AI106700 Cydney N. Johnson Diseases National Institute of Allergy and Infectious R01AI192221 Jason W. Rosch Diseases National Inst...	R37AI034885
Bloomberg Family Foundation
Johns Hopkins Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Antimalarial chemotherapy
Single oral dose ACT cure
Trioxane dimer orthoesters

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

Access to Document

10.1016/j.bmcl.2010.09.123

Cite this

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title = "A single, low, oral dose of a 5-carbon-linked trioxane dimer orthoester plus mefloquine cures malaria-infected mice",

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, Single oral dose ACT cure, Trioxane dimer orthoesters",

author = "Moon, \{Deuk Kyu\} and Abhai Tripathi and David Sullivan and Siegler, \{Maxime A.\} and Sean Parkin and Posner, \{Gary H.\}",

note = "Funding Information: We thank the NIH ( AI 34885 to G.H.P.), the Johns Hopkins Malaria Research Institute , and the Bloomberg Family Foundation for financial support (to G.H.P. and to D.S.). ",

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AU - Tripathi, Abhai

AU - Sullivan, David

AU - Siegler, Maxime A.

AU - Parkin, Sean

AU - Posner, Gary H.

N1 - Funding Information: We thank the NIH ( AI 34885 to G.H.P.), the Johns Hopkins Malaria Research Institute , and the Bloomberg Family Foundation for financial support (to G.H.P. and to D.S.).

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N2 - 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.

AB - 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.

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KW - Single oral dose ACT cure

KW - Trioxane dimer orthoesters

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A single, low, oral dose of a 5-carbon-linked trioxane dimer orthoester plus mefloquine cures malaria-infected mice

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

ASJC Scopus subject areas

Access to Document

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