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 I,2,4-trioxanes, which are related to the natural antimalarial ortemisinin, 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 (+)-7a, (-)-7a and (+)-7b, (-)-7b, showed the some level of in vitro antiparasitic activity.