Antimalarial peroxides: advances in drug discovery and design

Cyclic peroxides such as the plant-derived 1,2,4-trioxane artemisinin and its derivatives are short-lived, rapidly-acting antimalarials that are now usually combined with standard long-lived, alkaloidal antimalarials; such artemisinin combination therapy (ACT) is the worldwide standard operating procedure for malaria chemotherapy. This review discusses antimalarial monomeric and dimeric derivatives of artemisinin, peroxides not derived from artemisinin, and finally hybrids containing one peroxide unit covalently linked to a non-peroxide unit. Emphasis is placed on the antimalarial effectiveness of these diverse cyclic peroxides and on the simplicity of their synthesis.