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.
Monsieur Gérard AUDRAN (Institut de Chimie Radicalaire)
The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.
IHPE Interactions Hôtes-Pathogènes-Environnements
ICR Institut de Chimie Radicalaire
LCC-CNRS-K Laboratoire de Chimie de Coordination
LCC-CNRS-V Laboratoire de Chimie de Coordination
Help of the ANR 533,844 euros
Beginning and duration of the scientific project: January 2018 - 48 Months