A single, low, oral dose of a 5-carbon-linked trioxane dimer orthoester plus mefloquine cures malaria-infected mice.
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.
Department of Chemistry, Johns Hopkins University, Baltimore, MD 21218, USA.
Deuk Kyu
DK
Moon
Abhai
A
Tripathi
David
D
Sullivan
Maxime A
MA
Siegler
Sean
S
Parkin
Gary H
GH
Posner
D000284:Administration, Oral; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000627:therapeutic use*; D037621:Artemisinins / Q000627:therapeutic use; D018360:Crystallography, X-Ray; D004359:Drug Therapy, Combination; D004952:Esters / Q000737:chemistry / Q000627:therapeutic use*; D006571:Heterocyclic Compounds / Q000627:therapeutic use*; D006576:Heterocyclic Compounds, 4 or More Rings / Q000737:chemistry / Q000627:therapeutic use*; D008288:Malaria / Q000188:drug therapy; D015767:Mefloquine / Q000627:therapeutic use*; D051379:Mice; D015394:Molecular Structure; D010962:Plasmodium berghei / Q000187:drug effects*
C503429:1,2,4-trioxane; D000962:Antimalarials; D037621:Artemisinins; D004952:Esters; D006571:Heterocyclic Compounds; D006576:Heterocyclic Compounds, 4 or More Rings; C031327:artemisinin; D015767:Mefloquine