Dubin M, Fernandez Villamil S H, Stoppani A O
Centro de Investigaciones Bioenergéticas, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
Biochem Pharmacol. 1990 Apr 1;39(7):1151-60. doi: 10.1016/0006-2952(90)90256-k.
The lipophilic o-naphthoquinones beta-lapachone, 3,4-dihydro-2-methyl-2-ethyl-2H-naphtho[1,2b]pyran-5,6-dione (CG 8-935), 3,4-dihydro-2-methyl-2-phenyl-2H-naphtho[1,2b]pyran-5,6-dione (CG 9-442), and 3,4-dihydro-2,2-dimethyl-9-chloro-2H-naphtho[1,2b]pyran-5,6-dione (CG 10-248) (a) inhibited NADPH-dependent, iron-catalyzed microsomal lipid peroxidation; (b) prevented NADPH-dependent cytochrome P-450 destruction; (c) inhibited microsomal aniline 4-hydroxylase, aminopyrine N-demethylase and 7-ethoxycoumarin deethylase; (d) did not inhibit the ascorbate- and tert-butyl hydroperoxide-dependent lipid peroxidation and the cumenyl hydroperoxide-linked aniline 4-hydroxylase reaction; and (e) stimulated NADPH oxidation, superoxide anion radical generation and Fe(III)ADP reduction by NADPH-supplemented microsomes. In the presence of ascorbate, the same o-naphthoquinones stimulated oxygen uptake and semiquinone formation, as detected by ESR measurements. The p-naphthoquinones alpha-lapachone and menadione were relatively less effective than the o-naphthoquinones. These observations support the hypothesis that, in the micromolar concentration range, o-naphthoquinones inhibit microsomal lipid peroxidation and cytochrome P-450-catalyzed reactions, by diverting reducing equivalents from NADPH to dioxygen.
亲脂性邻萘醌类化合物β-拉帕醌、3,4-二氢-2-甲基-2-乙基-2H-萘并[1,2b]吡喃-5,6-二酮（CG 8-935）、3,4-二氢-2-甲基-2-苯基-2H-萘并[1,2b]吡喃-5,6-二酮（CG 9-442）以及3,4-二氢-2,2-二甲基-9-氯-2H-萘并[1,2b]吡喃-5,6-二酮（CG 10-248）：（a）抑制NADPH依赖的、铁催化的微粒体脂质过氧化；（b）防止NADPH依赖的细胞色素P-450破坏；（c）抑制微粒体苯胺4-羟化酶、氨基比林N-脱甲基酶和7-乙氧基香豆素脱乙基酶；（d）不抑制抗坏血酸和叔丁基过氧化氢依赖的脂质过氧化以及异丙苯过氧化氢连接的苯胺4-羟化酶反应；（e）刺激补充了NADPH的微粒体的NADPH氧化、超氧阴离子自由基生成以及Fe(III)ADP还原。在抗坏血酸存在的情况下，相同的邻萘醌类化合物刺激氧气摄取和半醌形成，这可通过电子自旋共振测量检测到。对萘醌类化合物α-拉帕醌和甲萘醌的效果相对不如邻萘醌类化合物。这些观察结果支持这样的假说，即在微摩尔浓度范围内，邻萘醌类化合物通过将还原当量从NADPH转移至双加氧，抑制微粒体脂质过氧化和细胞色素P-450催化的反应。
