title: Scavenging activity of aminoantipyrines against hydroxyl radical.
abstract: The pyrazolone derivatives antipyrine and 4-(N,N-dimethyl)-aminoantipyrine (aminopyrine) have long been used as analgesic, antipyretic and anti-inflammatory drugs. However, in spite of its recognized therapeutic benefits, the use of pyrazolones has been associated with agranulocytosis. Though the oxidation of aminopyrine by neutrophil-generated hypochlorous acid (HOCl), leading to the formation of a cation radical, has been considered responsible for the potential bone marrow toxicity, the reaction mechanisms of pyrazolones against other reactive oxygen species (ROS) remains elusive. Thus, the reactions of 4-aminoantipyrine and methylated derivatives with hydroxyl radicals (HO*) were studied as a model of their reactivity against ROS. The results show that 4-(N,N-dimethyl)-aminoantipyrine (aminopyrine) undergoes demethylation when reacting with HO. radical, leading to 4-(N-methyl)-aminoantipyrine, which is further demethylated to 4-aminoantipyrine. In addition, it was also observed that another favorable reaction of 4-aminoantipyrines in these conditions is the hydroxylation on the aromatic ring, a reaction that is common to aminopyrine, 4-(N-methyl)-aminoantipyrine, and 4-aminoantipyrine. Whether these reaction mechanisms give rise to harmful reactive intermediates requires further chemico-biological evaluation.
authors.affiliation: REQUIMTE, CQFB, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Campus de Caparica, 2829-516 Caparica, Portugal.
authors.forename: Pedro M P
authors.initials: PM
authors.lastname: Santos
authors.forename: Alexandra M M
authors.initials: AM
authors.lastname: Antunes
authors.forename: João
authors.initials: J
authors.lastname: Noronha
authors.forename: Eduarda
authors.initials: E
authors.lastname: Fernandes
authors.forename: Abel J S C
authors.initials: AJ
authors.lastname: Vieira
mesh_terms: D000675:Ampyrone / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D017665:Hydroxyl Radical / Q000737:chemistry* / Q000378:metabolism; D010084:Oxidation-Reduction
chemical_list: D016166:Free Radical Scavengers; D000675:Ampyrone; D017665:Hydroxyl Radical