Malaria-infected mice are cured by a single dose of novel artemisinin derivatives.
We disclose here for the first time the curative activity of a new generation of trioxane dimers, designed logically and prepared easily from the natural trioxane artemisinin in only four or five chemical steps that would be easily accomplished also on a manufacturing scale. Four of these trioxane dimers cure malaria-infected mice after only a single subcutaneous dose, and two other dimers cure after three oral doses.
Posner
Gary H
GH
Department of Chemistry, School of Arts and Sciences, The Johns Hopkins Malaria Research Institute, Johns Hopkins University, Baltimore, Maryland 21218, USA. ghp@jhu.edu
Paik
Ik-Hyeon
IH
Chang
Wonsuk
W
Borstnik
Kristina
K
Sinishtaj
Sandra
S
Rosenthal
Andrew S
AS
Shapiro
Theresa A
TA
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D037621:Artemisinins / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D008288:Malaria / Q000188:drug therapy* / Q000401:mortality; D051379:Mice; D010962:Plasmodium berghei; D013329:Structure-Activity Relationship
D000962:Antimalarials; D037621:Artemisinins; D019086:Bridged Bicyclo Compounds, Heterocyclic