New Orally Active Derivatives of Artemisinin with High Efficacy against Multidrug-Resistant Malaria in Mice
- 7 November 2006
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 49 (24) , 7227-7233
Abstract
A new series of ether derivatives of dihydroartemisinin have been prepared and evaluated for their antimalarial activity against multidrug-resistant Plasmodium yoeliinigeriensis 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 β-arteether (log P 3.84), and several of them are two- to four-fold more active than β-arteether. Among the ether derivatives, α-isomers are more active than the β-isomers. The ether derivatives 12α and 14α, the most active compounds of the series, provided 100% protection to infected mice at 12 mg/kg × 4 days. In this model β-arteether provides 100% and 20% protection at 48 mg/kg × 4 days and 24 mg/kg × 4 days, respectively.Keywords
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