Substrates for arachidonic acid co-oxidation with peroxidase/hydrogen peroxide. Further evidence for radical intermediates.
We tested the ability of a wide variety of organic compounds, including benzene and phenol derivatives, aromatic amines, pyrazoline derivatives and other non-steroidal anti-inflammatory drugs, to act as cosubstrates during the horseradish peroxidase/hydrogen peroxide-mediated oxygenation of arachidonic acid. Structural requirements for drug activation in our system proved to be an aromatic system and ring substitution by an easily oxidizable group. Complementary substituents modified drug activation. Among the phenol derivatives and aromatic amines we found the meta-substituted compounds to be significantly more effective than their ortho- and para-substituted analogues, indicating the involvement of radical intermediates in this type of reaction. The radical from 1-phenyl 3-methyl 2-pyrazolone(5) was detected by electron paramagnetic resonance spectroscopy. Kinetic studies on this radical were in good accordance with time-dependent measurement of arachidonic acid oxygenation.
Lehmann
F M
FM
Institut für Pharmakologie, Freie Universität Berlin, Federal Republic of Germany.
Bretz
N
N
von Bruchhausen
F
F
Wurm
G
G
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001711:Biotransformation; D002855:Chromatography, Thin Layer; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D006735:Horseradish Peroxidase / Q000378:metabolism; D006860:Hydrogen Bonding; D006861:Hydrogen Peroxide / Q000378:metabolism; D010084:Oxidation-Reduction; D004364:Pharmaceutical Preparations / Q000378:metabolism*
D001095:Arachidonic Acids; D005609:Free Radicals; D004364:Pharmaceutical Preparations; D016718:Arachidonic Acid; D006861:Hydrogen Peroxide; D006735:Horseradish Peroxidase