Water-soluble trioxanes as potent and safe antimalarial agents

Abstract

A series of synthetic C-3-aryl and C-12-benzyloxy 1,2,4-trioxane analogues is reported by Posner and co-workers to possess potent antimalarial activity versus Plasmodium falciparum in vitro and versus Plasmodium berghei in vivo in the mouse model of malaria. Several carboxylic acid containing derivatives within these two classes were shown to be superior to the semi-synthetic artemisinin derivative artelinic acid. In addition, one of the compounds claimed is not only more potent than artelinic acid in vivo but also has significantly higher water solubility and lower toxicity. On the basis of these encouraging results, these new, water-soluble peroxide analogues represent useful leads for further drug development.

• chemotherapy
• combination chemotherapy
• peroxide antimalarials
• trioxanes
• water-soluble