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  • Title: New orally active derivatives of artemisinin with high efficacy against multidrug-resistant malaria in mice.
    Author: Singh C, Chaudhary S, Puri SK.
    Journal: J Med Chem; 2006 Nov 30; 49(24):7227-33. PubMed ID: 17125275.
    Abstract:
    A new series of ether derivatives of dihydroartemisinin have been prepared and evaluated for their antimalarial activity against multidrug-resistant Plasmodium yoelii nigeriensis in mice by oral route. These new derivatives 7-17 are highly lipophilic (log P in the range of 5.51 to 7.19) as compared with beta-arteether (log P 3.84), and several of them are two- to four-fold more active than beta-arteether. Among the ether derivatives, alpha-isomers are more active than the beta-isomers. The ether derivatives 12alpha and 14alpha, the most active compounds of the series, provided 100% protection to infected mice at 12 mg/kgx4 days. In this model beta-arteether provides 100% and 20% protection at 48 mg/kgx4 days and 24 mg/kgx4 days, respectively.
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