Inhibitory effect of various organophosphorus esters on rat liver malathion carboxylesterase in vitro: role of mixed-function oxidases.
6 Structurally related trialkyl phosphorothioates were assessed for their inhibitory effects on rat liver malathion carboxylesterase in vitro. IC50 values indicate that all these compounds, except compound III, a phosphorodithioate, inhibited the activity of the enzyme progressively with increasing incubation time of the compounds with the enzyme preparation. Compounds with an ethyl substitution were more potent than the corresponding methyl-substituted inhibitors. There was cytochrome P-450-mediated oxidative deactivation of all compounds tested, this was especially profound with inhibitors containing an ethyl thiolate moiety.
D000818:Animals; D001711:Biotransformation; D002265:Carboxylic Ester Hydrolases / Q000037:antagonists & inhibitors*; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D063086:Organothiophosphates / Q000378:metabolism / Q000494:pharmacology*; D009946:Organothiophosphorus Compounds / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
D063086:Organothiophosphates; D009946:Organothiophosphorus Compounds; D009249:NADP; D006899:Mixed Function Oxygenases; D002265:Carboxylic Ester Hydrolases; C021528:malathion esterases