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  • Title: Malaria-infected mice are cured by oral administration of new artemisinin derivatives.
    Author: Posner GH, Chang W, Hess L, Woodard L, Sinishtaj S, Usera AR, Maio W, Rosenthal AS, Kalinda AS, D'Angelo JG, Petersen KS, Stohler R, Chollet J, Santo-Tomas J, Snyder C, Rottmann M, Wittlin S, Brun R, Shapiro TA.
    Journal: J Med Chem; 2008 Feb 28; 51(4):1035-42. PubMed ID: 18232653.
    Abstract:
    In four or five chemical steps from the 1,2,4-trioxane artemisinin, a new series of 23 trioxane dimers has been prepared. Eleven of these new trioxane dimers cure malaria-infected mice via oral dosing at 3 x 30 mg/kg. The clinically used trioxane drug sodium artesunate prolonged mouse average survival to 7.2 days with this oral dose regimen. In comparison, animals receiving no drug die typically on day 6-7 postinfection. At only 3 x 10 mg/kg oral dosing, seven dimers prolong the lifetime of malaria-infected mice to days 14-17, more than double the chemotherapeutic effect of sodium artesunate. Ten new trioxane dimers at only a single oral dose of 30 mg/kg prolong mouse average survival to days 8.7-13.7, and this effect is comparable to that of the fully synthetic trioxolane drug development candidate OZ277, which is in phase II clinical trials.
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