Work

Stable free radical and benzoquinone imine metabolites of an acetaminophen analogue.

Year: 1984

Type: article

Abstract: The enzymatic oxidation of the acetaminophen analogue 3',5'-dimethyl-4'-hydroxyacetanilide (3',5'-dimethylacetaminophen) with the horseradish peroxidase/hydrogen peroxide system forms a phenoxyl free radical metabolite. The structure of this free radical is established by a complete analysis of the ESR spectrum and confirmed by deuterium isotope substitution. Concomitant with phenoxyl radical formation, N-acetyl-3,5-dimethyl-p-benzoquinone imine was detected by optical spectroscopy. The free radical is also formed by comproportionation in solutions of the quinone imine containing added 3',5'-dimethylacetaminophen. In contrast to acetaminophen, the imine and radical metabolites are stable and can be detected without resort to rapid-mixing techniques. Factors leading to the increased stability of these metabolites relative to those formed from acetaminophen are discussed in terms of the toxicity of acetaminophen.

Source: Journal of Biological Chemistry

DOI: 10.1016/s0021-9258(18)90961-0

Authors: V Fischer, R P Mason

Institutions: National Institutes of Health, National Institute of Environmental Health Sciences

Language: English

Topic: Bioactive Compounds and Antitumor Agents

Subfield: Toxicology

Field: Pharmacology, Toxicology and Pharmaceutics

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,430