Malaria-infected mice live until at least day 30 after a new monomeric trioxane combined with mefloquine are administered together in a single low oral dose.
In only five simple steps and 48% overall yield from the natural trioxane artemisinin, the thermally and hydrolytically stable trioxane fluoroanilide 4b has been prepared. Upon one oral dose of only 6.8 mg/kg of monomeric trioxane 4b combined with 20 mg/kg of mefloquine hydrochloride, all of the malaria-infected mice lived until at least day 30 post infection. Of the five mice in this surviving group, four (80%) were completely cured (no parasites in their blood) and one mouse had 4% blood parasitemia. Importantly, the efficacy of this ACT chemotherapy using monomeric trioxane 4b plus mefloquine hydrochloride is considerably better than the efficacy under the same conditions using the popular trioxane drug artemether plus mefloquine hydrochloride.
Woodard
Lauren E
LE
Department of Chemistry, School of Arts and Sciences, The Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218-2685, USA.
Chang
Wonsuk
W
Chen
Xiaochun
X
Liu
Jun O
JO
Shapiro
Theresa A
TA
Posner
Gary H
GH
D000284:Administration, Oral; D000577:Amides / Q000737:chemistry; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use*; D019281:Dimerization; D004338:Drug Combinations; D006571:Heterocyclic Compounds / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use*; D008288:Malaria / Q000188:drug therapy*; D008297:Male; D015767:Mefloquine / Q000008:administration & dosage* / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D016019:Survival Analysis; D013997:Time Factors
D000577:Amides; D000962:Antimalarials; D004338:Drug Combinations; D006571:Heterocyclic Compounds; C011374:s-trioxane; D015767:Mefloquine