Scavenging activity of aminoantipyrines against hydroxyl radical.
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| 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.
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| Authors | Pedro M P Santos, Alexandra M M Antunes, João Noronha, Eduarda Fernandes, Abel J S C Vieira |
| Journal | European journal of medicinal chemistry (Eur J Med Chem) Vol. 45 Issue 6 Pg. 2258-64 (Jun 2010) ISSN: 1768-3254 [Electronic] France |
| PMID | 20172632 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright (c) 2010 Elsevier Masson SAS. All rights reserved. |
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