RT Journal Article
SR Electronic
T1 Reduction and glutathione conjugation reactions of N-acetyl-p-benzoquinone imine and two dimethylated analogues.
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 151
OP 157
VO 25
IS 1
A1 Rosen, G M
A1 Rauckman, E J
A1 Ellington, S P
A1 Dahlin, D C
A1 Christie, J L
A1 Nelson, S D
YR 1984
UL http://molpharm.aspetjournals.org/content/25/1/151.abstract
AB N-Acetyl-3,5-dimethyl-p-benzoquinone imine, N-acetyl-2,6-dimethyl-p-benzoquinone imine, and N-acetyl-p-benzoquinone imine were synthesized via the oxidation of 3,5-dimethylacetaminophen, 2,6-dimethylacetaminophen, and acetaminophen, respectively. All three quinone imines were rapidly reduced to their corresponding semiquinone imines by NADPH-cytochrome P-450 reductase. All three benzoquinone imines underwent comproportionation with their respective phenols to yield the corresponding semiquinone imines, which in the presence of oxygen gave superoxide. Identification of this latter free radical was based on spin-trapping techniques. Reduced GSH was found to be an excellent nucleophile toward N-acetyl-2,6-dimethyl-p-benzoquinone imine, whereas this thiol behaved as a one-electron reductant toward N-acetyl-3,5-dimethyl-p-benzoquinone imine. Finally, GSH was determined to act as both a nucleophile and a reductant toward N-acetyl-p-benzoquinone imine.