Reaction between Ferriprotoporphyrin IX and the Antimalarial Endoperoxide Artesunate Gives an Intermediate Species with Enhanced Redox Catalytic Activity

Abstract

Abstract The kinetics of the reaction between ferri(Fe(III) protoporphyrin IX (haemin) and the potent sesquiterpene endoperoxide antimalarial artesunate are shown to be consistent with a three-step, two-intermediate mechanism, with the final product possessing a degraded tetrapyrrole ring system. Microscopic rate constants for the mechanism have been evaluated. The redox catalytic capability of the haem artesunate complex is shown to be approximately fourfold that of haemin alone, suggesting a possible mechanism of action of the drug.