Inhibition of glutathione- S- aryltransferase from rat liver by organogermanium, lead and tin compounds

Abstract

Compounds having three carbon—germanium, carbon—tin or carbon—lead bonds were found to be effective inhibitors of rat liver glutathione- S-aryltransferase activity with K i, values in the μM range. Classical competitive inhibition was observed with l,2-dichloro-4-nitrobenzene as the limiting substrate. However, when the second substrate, glutathione, was limiting, inhibition of the mixed type occurred. Within the metallic series IVb, triethylsilane chloride was not active, while the effectiveness as inhibitors increased through triethylgermanium chloride, triethyltin bromide and triethyllead chloride. Except in the case of sulfur, the fourth group or atom bonded to tin in a series of triphenyltin compounds had little effect on inhibitory activity. Sodium sulfide or 2,3-dimercapto-1-propanol (BAL) was capable of protecting glutathione- S-aryltransferase from inhibition by triphenyltin chloride. Glutathione conjugations at aromatic carbon atoms were much more sensitive to inhibition by organotins than were conjugations at alkyl carbons or epoxides.