Antimalarial chemotherapy: artemisinin-derived dimer carbonates and thiocarbonates

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

doi:10.1016/j.bmcl.2014.04.025

Antimalarial chemotherapy: artemisinin-derived dimer carbonates and thiocarbonates

Bioorg Med Chem Lett. 2014 Jun 1;24(11):2440-3. doi: 10.1016/j.bmcl.2014.04.025. Epub 2014 Apr 16.

Authors

Jennifer R Mazzone¹, Ryan C Conyers¹, 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

Several 2-carbon-linked trioxane dimer secondary alcohol carbonates 14 and thiocarbonates 15, combined with mefloquine and administered in a low single oral dose, prolonged the survival times of malaria-infected mice much more effectively than the popular monomeric antimalarial drug artemether plus mefloquine. Three dimer carbonates 14 and one dimer thiocarbonate 15 partially cured malaria-infected mice.

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

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antimalarials / administration & dosage
Antimalarials / chemistry
Antimalarials / therapeutic use*
Artemisinins / chemistry*
Carbonates / administration & dosage
Carbonates / chemistry
Carbonates / therapeutic use*
Dimerization
Disease Models, Animal
Dose-Response Relationship, Drug
Malaria / drug therapy*
Male
Mice
Mice, Inbred C57BL
Molecular Structure
Parasitic Sensitivity Tests
Plasmodium berghei / drug effects*
Structure-Activity Relationship
Sulfhydryl Compounds / administration & dosage
Sulfhydryl Compounds / chemistry
Sulfhydryl Compounds / therapeutic use*

Substances

Antimalarials
Artemisinins
Carbonates
Sulfhydryl Compounds
artemisinin

Abstract

Publication types

MeSH terms

Substances

Grants and funding