[Interaction of bis-phosphorylated methanes with mammalian esterases].

The interaction of human erythrocyte acetylcholinesterase, horse serum butyrylcholinesterase and rat liver carboxylesterase with insecticides (RO)2P(O)SCH(COOEt)SP(O)(OR)2 (I) and (RO)2P(O)SCH(COOEt)OP(S)(OR)2 (II) was studied. The type I and II compounds were not hydrolyzed by carboxylesterase and inhibited the esterases irreversibly. A complex pattern of inhibition of acetylcholinesterase and butyrylcholinesterase by these compounds was caused by kinetically-manifested formation of an enzyme-inhibitor complex. The compounds I and II were more selective towards butyrylcholinesterase than towards acetylcholinesterase and carboxylesterase (kII two orders of magnitude higher) because of effective binding in the butyrylcholinesterase active center (K alpha 10(-8)--10(-9) M) due to hydrophobic interaction. An important role of the thion-phosphoryl-containing fragment in the interaction of type II compounds with hydrophobic sites of butyrylcholinesterase and carboxylesterase active centers was established.