Abstract

Objective: Febrifugine, a quinazoline alkaloid isolated from Dichroa febrifuga roots, shows powerful antimalarial activity against Plasmodium falciparum. This review aimed to illustrate structural aspects of the naturally occurring febrifugine (1) and isofebrifugine (2) and how these issues were ultimately resolved by chemical synthesis. Materials and methods: Although the use of ferifugine as an antimalarial drug has been precluded because of its severe side effects, its potent antimalarial activity has stimulated medicinal chemists to pursue its derivatives instead, which may provide valuable leads for novel antimalarial drugs. This review summarizes historical isolation studies and the chemistry performed which culminated in the correct structural elucidation of naturally occurring febrifugine and its isomer isofebrifugine. It also includes the range of febrifugine analogues prepared for antimalarial evaluation. Results: The range of analogues of (1) prepared for malarial programmes has been highlighted. It is notable that despite the substantial body of literature surrounding febrifugine and isofebrifugine, the detailed biological mechanism, or mechanisms for their antiprotozoal activity are not completely known. Conclusion: Furthermore, many of the more recent biological studies involving febrifugine have been performed using racemic material, as opposed to single optical isomers.

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