Diphenylamine as an important structure of nonsteroidal anti-inflammatory drugs to uncouple mitochondrial oxidative phosphorylation

被引：44

作者：

Masubuchi, Y ^{[1
]}

Yamada, S ^{[1
]}

Horie, T ^{[1
]}

机构：

[1] Chiba Univ, Fac Pharmaceut Sci, Lab Biopharmaceut, Inage Ku, Chiba 2638522, Japan

来源：

BIOCHEMICAL PHARMACOLOGY | 1999年 / 58卷 / 05期

关键词：

oxidative phosphorylation; uncoupler; mitochondria; nonsteroidal anti-inflammatory drugs; diphenylamine;

D O I：

10.1016/S0006-2952(99)00163-X

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

A marked difference has been observed in the inhibitory effects of nonsteroidal antiinflammatory drugs (NSAIDs) on oxidative phosphorylation of rat liver mitochondria. It should be noted that some of the potent inhibitors, N-phenylanthranilic acids and diclofenac, have a similar "skeleton" structure, diphenylamine. Diphenylamine itself was found to inhibit oxidative phosphorylation significantly, although its inhibition potency was weaker than that of NSAIDs with a diphenylamine structure. In addition to decreases in the respiration control index (ratio of state 3 to state 4 respiration), these compounds released oligomycin-inhibited state 3 respiration. These results demonstrated that diphenylamine, as well as N-phenylanthranilic acids and diclofenac, was an uncoupler of oxidative phosphorylation of rat liver mitochondria. Thus, diphenylamine was suggested to play an important role in the uncoupling effects of NSAIDs with a diphenylamine skeleton. (C) 1999 Elsevier Science Inc.

引用

页码：861 / 865

页数：5

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