title: Antimalarial bicyclic peroxides belonging to the G-factor family: mechanistic aspects of their formation and iron (II) induced reduction.
abstract: Artemisinin and its derivatives are peroxide-containing compounds targeting P. falciparum. We review here structural analogues of bicyclic peroxides belonging to the G factors family presenting antimalarial properties. They were synthesised under Mannich type conditions, followed by an autoxidation step resulting exclusively in the peroxide. As the electron transfer from haem or free iron to the peroxide is the first step in the mode of action of artemisinin-like compounds, the redox properties of some endoperoxides were studied by electrochemistry allowing the evaluation of the reduction standard potentials. The Fe(II) induced reduction was also investigated and the reactivity of the C-centered radical intermediate formed was linked to the antimalarial activity. These bicyclic peroxides both with various hybrid molecules containing the endoperoxide framework were evaluated in vitro against Plasmodium falciparum. They exhibited moderate to good activities.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Ruiz
authors.forename: Joelle
authors.initials: J
authors.lastname: Azema
authors.forename: Corinne
authors.initials: C
authors.lastname: Payrastre
authors.forename: Michel
authors.initials: M
authors.lastname: Baltas
authors.forename: Beatrice
authors.initials: B
authors.lastname: Tuccio
authors.forename: Henri
authors.initials: H
authors.lastname: Vial
authors.affiliation: Laboratoire de Synthese et de Physicochimie de Molecules d'Interet Biologique, UMR CNRS 5068, Universite Paul-Sabatier, 118 route de Narbonne, F-31062 Toulouse Cedex 04, France. candre@chimie.ups-tlse.fr.
authors.forename: Christiane
authors.initials: C
authors.lastname: Andre-Barres
mesh_terms: D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000737:chemistry / Q000494:pharmacology*; D007501:Iron / Q000737:chemistry*; D010084:Oxidation-Reduction; D010545:Peroxides / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000962:Antimalarials; D001643:Bridged Bicyclo Compounds; D010545:Peroxides; D007501:Iron