Diphenylamine as an important structure of nonsteroidal anti-inflammatory drugs to uncouple mitochondrial oxidative phosphorylation††Abbreviations: NSAIDs, nonsteroidal anti-inflammatory drugs; and MPT, mitochondrial permeability transition.
1999; Elsevier BV; Volume: 58; Issue: 5 Linguagem: Inglês
10.1016/s0006-2952(99)00163-x
ISSN1873-2968
AutoresYasuhiro Masubuchi, Shoko M. Yamada, Toshiharu Horie,
Tópico(s)Traditional Chinese Medicine Analysis
ResumoA marked difference has been observed in the inhibitory effects of nonsteroidal anti-inflammatory 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.
Referência(s)