Inhibition of succinoxidase and reduced nicotinamide adenine dinucleotide (NADH) oxidase by 2,3-ethlenedioxy-1,4-benzoquinones having alkylthio and arythio side chains.

Abstract

A series of 2, 3-ethylenedioxy-1, 4-benzoquinones having an alkylthio or arylthio side chain at the 5-position or two alkylthio or arylthio side chains at the 5, 6-positions was synthesized. These compounds were tested for inhibition of the succinoxidase and reduced nicotinamide adenine dinucleotide (NADH) oxidase systems in the mitochondrial respiratory chain. 5-Arylthio- and 5, 6-diarylthio-2, 3-ethylenedioxy-1, 4-benzoquinones were found to show potent inhibitory activities toward both enzyme systems. However, 5-alkylthio- and 5, 6-dialkylthio-2, 3-ethylenedioxy-1, 4-benzoquinones showed weak inhibitory activities. The substitution of a 2, 3-ethylenedioxy group in place of the 2, 3-dimethoxy group of coenzyme Q (CoQ) was found to be more favorable than the previously reported 2, 3-dimethyl compound or 1, 4-naphthoquinones for the inhibition of both enzyme systems. The effects of 2, 3-ethylenedioxy-1, 4-benzoquinones on the reduced minus oxidized difference spectra of submitochondrial particles with succinate or NADH as a substrate were investigated to identify their inhibitory sites in the respiratory chain. The spectral changes suggested that 5-arylthio- and 5, 6-diarylthio-2, 3-ethylenedioxy-1, 4-benzoquinones inhibit some sites between succinate and CoQ, as well as after cytochrome a+a3. On the other hand, 5, 6-dialkylthio-2, 3-ethylenedioxy-1, 4-benzoquinones were found to inhibit some sites between NADH and CoQ, as well as after chrochrome a+a3.