REDUCTION AND GLUTATHIONE CONJUGATION REACTIONS OF N-ACETYL-PARA-BENZOQUINONE IMINE AND 2 DIMETHYLATED ANALOGS

  • 1 January 1984
    • journal article
    • research article
    • Vol. 25  (1) , 151-157
Abstract
The widely used analgesic acetaminophen causes hepatic necrosis in humans and experimental animals after high doses have been administered. 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 3 quinone imines were rapidly reduced to their corresponding semiquinone imines by NADPH-cytochrome P-450 reductase. All 3 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 [glutathione] was an excellent nucleophile toward N-acetyl-2,6-dimethyl-p-benzoquinone imine, whereas this thiol behaved as a 1-electron reductant toward N-acetyl-3,5-dimethyl-p-benzoquinone imine. GSH acted as both a nucleophile and a reductant toward N-acetyl-p-benzoquinone imine.