Mechanism-based design of new trioxanes for chemotherapy of malaria and cancer

ORGN 274

Gary H. Posner, Department of Chemistry, Department of Chemistry, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218
Understanding the chemical mechanism of action for 1,2,4-trioxanes like the natural antimalarial artemisinin has enabled rational design of new analogs. Several of these new trioxanes are orally efficacious antimalarials in rodents and have a better therapeutic index than the clinically used trioxane sodium artesunate. Several of these new trioxane dimers have also potent and selective inhibitory activity on the growth of cancer cells. Discussion will be presented concerning fundamental mechanism of action, mechanism-based design of new trioxanes, in vivo testing results, and potential for chemotherapy of malaria and cancer