title: ESR detection of free radical intermediates during autoxidation of 5-hydroxyprimaquine.
abstract: Autoxidation of 5-hydroxyprimaquine, a putative metabolite of the antimalarial primaquine, was studied by oxygen consumption and ESR spectroscopy. 5-Hydroxyprimaquine underwent fast autoxidation under mild conditions (pH 7.4-8.5, 25 degrees C, and presence of 1 mM diethylenetriamine pentaacetic acid); each mol of the drug consumed 0.75 mol of oxygen and formed 0.5 mol of hydrogen peroxide. Direct-ESR experiments demonstrated that 5-hydroxyprimaquine autoxidation was accompanied by generation of a drug-derived free radical that is oxygen sensitive. Generation of hydroxyl radical was also established by spin-trapping experiments in the presence of 5,5-dimethyl-1-pyrroline N-oxide. The effect of antioxidant enzymes on hydroxyl radical adduct yield and analysis of autoxidation stoichiometry suggest that the main route for hydroxyl radical generation is the iron-catalyzed reaction between the drug-derived free radical and hydrogen peroxide.
authors.affiliation: Biochemistry Department, Universidade de São Paulo, Brazil.
authors.forename: J
authors.initials: J
authors.lastname: Vasquez-Vivar
authors.forename: O
authors.initials: O
authors.lastname: Augusto
mesh_terms: D003497:Cyclic N-Oxides; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D006878:Hydroxides; D017665:Hydroxyl Radical; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D011319:Primaquine / Q000031:analogs & derivatives*; D013113:Spin Labels
chemical_list: D003497:Cyclic N-Oxides; D005609:Free Radicals; D006878:Hydroxides; D013113:Spin Labels; D017665:Hydroxyl Radical; C056497:5-hydroxyprimaquine; C017245:5,5-dimethyl-1-pyrroline-1-oxide; D011319:Primaquine