Rosen G M, Rauckman E J, Ellington S P, Dahlin D C, Christie J L, Nelson S D
Mol Pharmacol. 1984 Jan;25(1):151-7.
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.
N-乙酰基-3,5-二甲基对苯醌亚胺、N-乙酰基-2,6-二甲基对苯醌亚胺和N-乙酰基对苯醌亚胺分别通过3,5-二甲基对乙酰氨基酚、2,6-二甲基对乙酰氨基酚和对乙酰氨基酚的氧化反应合成。这三种醌亚胺均被NADPH-细胞色素P-450还原酶迅速还原为相应的半醌亚胺。这三种苯醌亚胺均与各自的酚发生歧化反应生成相应的半醌亚胺，后者在有氧条件下产生超氧化物。后一种自由基的鉴定基于自旋捕获技术。发现还原型谷胱甘肽（GSH）是N-乙酰基-2,6-二甲基对苯醌亚胺的优良亲核试剂，而这种硫醇对N-乙酰基-3,5-二甲基对苯醌亚胺表现为单电子还原剂。最后，确定GSH对N-乙酰基对苯醌亚胺既起亲核试剂作用又起还原剂作用。
