Radical-based therapeutic strategy to fight parasitic diseases – RADICAL

The present project is based on a new concept using the chemical properties of radical species to fight both malaria and schistosomiasis diseases. Our project is focused on the preparation of a stable prodrug (alkoxyamine as dormant radical, R1R2NOR3), which will be selectively coordinated by the free FeII-heme (addressing system) released after the digestion of Human hemoglobin by the blood parasites. This selective coordination will then instantaneously activate the homolysis of the FeII-heme linked-alkoxyamine (activation) and generate highly reactive radical species (drug): a nitroxyl radical (R1R2NO•) and an alkyl radical (•R3). These radical species will cause irreversible biological disorders by radical mechanisms inside of parasite until its death. Thus, the key-point of this work is both to generate selectively radical species using the heme metabolism and take the advantage of the broad and powerful reactivity of radicals to cure patients by parasitic diseases. Thus, we propose to design and to develop a drug series curative of both malaria and schistosomiasis human blood parasites that are frequently met in tropical countries.