Inhibition of mitochondrial respiratory chain by arylthiolated 2,3-ethylenedioxy-1,4-benzoquinones.

A series of arylthiolated 2,3-ethylenedioxy-1,4-benzoquinones as a coenzyme Q (CoQ) antagonist was tested for inhibition of succinate oxidase and reduced nicotinamide adenine dinucleotide (NADH) oxidase systems in the mitochondrial respiratory chain. The following characteristics were revealed: (1) 2,3-ethylenedioxy, 5-arylthio and 5,6-diarylthio groups were confirmed to be favorable for inhibition of both systems; (2) these analogs were more effective in the succinate oxidase system than in the NADH oxidase system; (3) 4' substituents on the benzene side ring had little effect on inhibitory activity; (4) the acting sites of these analogs had no strict stereospecificity. The reduced minus oxidized difference spectra revealed that these analogs inhibited the succinate oxidase system at the site between succinate and CoQ, and the NADH oxidase system at the site after cytochrome a + a3, suggesting these analogs might act as antagonists of CoQ in the succinate oxidase system. However, 5-(4'-nitrophenylthio)-2,3-ethylenedioxy-1,4-benzoquinone (If) strongly inhibited only the succinate oxidase system at the site after cytochrome a + a3.