Quinones and their Glutathione Conjugates as Irreversible Inhibitors of Glutathione S-Transferases

Abstract

Quinones are known for their reactivity towards sulfhydryl groups, and thus are potential protein alkylating compounds. Human exposure to these compounds arises either from naturally occurring quinones or from quinones formed as metabolites from aromatic compounds. Normally, quinones are detoxified by conjugation with glutathione, producing the hydroquinone conjugates. Certain quinones, however, retain their oxidized nature after conjugation (e.g. halogen substituted quinones), while the hydroquinone conjugates have been shown to undergo intracellular oxidation. Thus, glutathione conjugates of quinones are formed, which display a special type of reactivity, i.e. selective inhibition of glutathione S-transferase isoenzymes (GST). This paper describes the development and use of glutathione conjugates of chlorinated benzoquinones as inhibitors of glutathione S-transferases.