Inhibition of mitochondrial respiratory chain by alkylthiolated 2,3-dicyano-1,4-benzoquinones.

A series of alkylthiolated 2,3-dicyano-1,4-benzoquinones was synthesized and tested for the effects on the respiratory chain in beef heart mitochondria as an antimetabolite of ubiquinones (coenzyme Q). It was proved that these analogs are among the best inhibitors of both succinate oxidase and NADH oxidase systems. The introduction of a 2,3-dicyano group to the quinone ring was found to be more favorable for inhibitory activity than 2,3-dimethoxy, 2,3-dimethyl groups and bicyclic quinones such as 2,3-ethylenedioxy-1,4-benzoquinones and 1,4-naphthoquinones. The inhibitory activity was minimally sensitive to the length of the alkylthio side-chain. On the other hand, the difference spectra of reduced minus oxidized forms of cytochromes were investigated to identify the inhibitory site, suggesting that alkylthiolated 2,3-dicyano-1,4-benzoquinones inhibit at sites between the substrates (succinate and NADH) and cytochrome b, and at the site after cytochrome a + a3 in the respiratory chain.