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  • Title: Synthesis and biological evaluation of febrifugine analogues as potential antimalarial agents.
    Author: Zhu S, Zhang Q, Gudise C, Wei L, Smith E, Zeng Y.
    Journal: Bioorg Med Chem; 2009 Jul 01; 17(13):4496-502. PubMed ID: 19467876.
    Abstract:
    Febrifugine is an alkaloid isolated from Dichroa febrifuga Lour as the active component against Plasmodium falciparum. Adverse side effects have precluded febrifugine as a potential clinical drug. In this study novel febrifugine analogues were designed and synthesized. Lower toxicity was achieved by reducing or eliminating the tendency of forming chemically reactive and toxic intermediates and metabolites. Synthesized compounds were evaluated for acute toxicity and in vitro and in vivo antimalarial efficacy. Some compounds are much less toxic than the natural product febrifugine and existing antimalarial drug chloroquine and are expected to possess wide therapeutic windows. These compounds, as well as the underlying design rationale, may find usefulness in the discovery and development of new antimalarial drugs.
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