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

Bioorg Med Chem Lett. 2011 May 1;21(9):2773-5. doi: 10.1016/j.bmcl.2010.09.123. Epub 2010 Sep 29.

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.

Publication types

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

MeSH terms

  • Administration, Oral
  • Animals
  • Antimalarials / administration & dosage
  • Antimalarials / therapeutic use*
  • Artemisinins / therapeutic use
  • Crystallography, X-Ray
  • Drug Therapy, Combination
  • Esters / chemistry
  • Esters / therapeutic use*
  • Heterocyclic Compounds / therapeutic use*
  • Heterocyclic Compounds, 4 or More Rings / chemistry
  • Heterocyclic Compounds, 4 or More Rings / therapeutic use*
  • Malaria / drug therapy
  • Mefloquine / therapeutic use*
  • Mice
  • Molecular Structure
  • Plasmodium berghei / drug effects*

Substances

  • 1,2,4-trioxane
  • Antimalarials
  • Artemisinins
  • Esters
  • Heterocyclic Compounds
  • Heterocyclic Compounds, 4 or More Rings
  • artemisinin
  • Mefloquine