Antimalarial chemotherapy: orally curative artemisinin-derived trioxane dimer esters

Ryan C Conyers; Jennifer R Mazzone; Abhai K Tripathi; David J Sullivan; Gary H Posner

doi:10.1016/j.bmcl.2014.11.064

Antimalarial chemotherapy: orally curative artemisinin-derived trioxane dimer esters

Bioorg Med Chem Lett. 2015 Jan 15;25(2):245-8. doi: 10.1016/j.bmcl.2014.11.064. Epub 2014 Nov 27.

Authors

Ryan C Conyers¹, Jennifer R Mazzone¹, Abhai K Tripathi², David J Sullivan², Gary H Posner³

Affiliations

¹ Department of Chemistry, School of Arts and Sciences, The Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, United States.
² W. Harry Feinstone, Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD 21205, United States; The Johns Hopkins Malaria Research Institute, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD 21205, United States.
³ Department of Chemistry, School of Arts and Sciences, The Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, United States; The Johns Hopkins Malaria Research Institute, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD 21205, United States. Electronic address: [email protected].

Abstract

Eight new artemisinin-derived trioxane dimer esters 5 have been prepared and tested for antimalarial efficacy in malaria-infected mice. At a single oral dose of only 6mg/kg combined with 18mg/kg of mefloquine, each of the dimer esters 5 outperformed the antimalarial drug artemether (2). The most efficacious dimer, dichlorobenzoate ester 5h, prolonged mouse survival past day 30 of infection with three of the four mice in this group having no detectable parasitemia and appearing and acting healthy on day 30.

Keywords: Antimalarial chemotherapy; Oral bioavailability; Single oral dose ACT; Trioxane dimer esters.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Administration, Oral
Animals
Antimalarials / administration & dosage*
Antimalarials / chemistry*
Artemisinins / administration & dosage*
Artemisinins / chemistry*
Dimerization
Malaria / drug therapy*
Mice
Plasmodium berghei / drug effects*

Substances

Antimalarials
Artemisinins
artemisinin

Abstract

Publication types

MeSH terms

Substances

Grants and funding