Orally active esters of dihydroartemisinin: Synthesis and antimalarial activity against multidrug-resistant Plasmodium yoelii in mice

ArticleinBioorganic & medicinal chemistry letters 18(4):1436-41 · March 2008with11 Reads
Impact Factor: 2.42 · DOI: 10.1016/j.bmcl.2007.12.074 · Source: PubMed

    Abstract

    A series of artemisinin derived esters 7a-j, incorporating pharmacologically privileged substructure, such as biphenyl, adamantane and fluorene, have been prepared and evaluated for antimalarial activity against multidrug-resistant (MDR) Plasmodium yoelii nigeriensis by oral route. Several of these compounds were found to be more active than the antimalarial drugs beta-arteether 4 and artesunic acid 5. Ester 7i, the most active compound of the series, provided 100% and 80% protection to the infected mice at 24 mg/kg x 4 days and 12 mg/kg x 4 days, respectively. In this model beta-arteether provided 100% and 20% protection at 48 mg/kg x 4 days and 24 mg/kg x 4 days, respectively.