Inhibition of Mitochondrial Respiration by a para-Quinone Methide

Abstract

A relatively stable para quinone methide was prepared from 4-allyl-2,6-dimethoxyphenol. In aqueous solution the quinone methide had a half-life of 52 min, yet reacted rapidly with thiols such as glutathione or cysteine. The unusual stability of this quinone methide allowed us to directly test its effects on mitochondrial respiration. The quinone methide was a potent inhibitor of succinate-dependent mitochondrial respiration (IC 50 = 47 μM). The inhibition appeared to be due to the depletion of protein thiols, since its effects were comparable to 5,5′-dithiobis(2-nitrobenzoic acid) (DTNB, Ellman′s reagent). This quinone methide may prove a useful tool in the investigation of the specific effects of quinone methides on cells which lead to cytotoxicity.