Enantiomeric 1,2,4-Trioxanes Display Equivalent in vitro Antimalarial Activity Versus Plasmodium falciparum Malaria Parasites: Implications for the Molecular Mechanism of Action of the Artemisinins

The aim of this study was to synthesise pure enantiomers of potent antimalarial 1,2,4-trioxanes, which are related to the natural antimalarial artemisinin, and then to assay each against a panel of Plasmodium falciparum strains. The working hypothesis was that if the artemisinin derivatives interact with a specific protein-target site, then there should be stereoselective differences in their activity. In five different P. falciparum isolates, however, the trioxane enantiomers (+)-7 a, (−)-7 a and (+)-7 b, (−)-7 b, showed the same level of in vitro antiparasitic activity.