Fluorinated aldehydes and ketones acting as quasi-substrate inhibitors of acetylcholinesterase.
1. The inhibition of acetylcholinesterase (acetylcholine hydrolase, EC 3.1.1.7) by compounds containing trifluoromethyl-carbonyl groups was investigated and related to the effects observed with structurally similar, non-fluorinated chemicals. 2. Compounds that in aqueous solution readily form hydrates inhibit acetylcholinesterase in a time-dependent process. On the other hand non-hydrated, carbonyl-containing compounds showed rapid and reversible, time-independent enzyme inactivation when assayed under steady state conditions. 3. m-N,N,N-Trimethylammonium-acetophenone acts as a rapid and reversible, time-independent, linear competitive inhibitor of acetylcholinesterase (Ki = 5.0 . 10(-7) M). 4. The most potent enzyme inhibitor tested in this series was N,N,N,-trimethylammonium-m-trifluoroacetophenone. It gives time-dependent inhibition and the concentration which inactivates eel acetylcholinesterase to 50% of the original activity after 30 min exposure is 1.3 . 10(-8) M. The bimolecular rate constant for this reaction is 1.8 . 10(6) 1 . mol-1 . min-1. The enzyme-inhibitor complex is very stable as the inhibited enzyme after 8 days of dialysis is reactivated to 20% only. This compound represents a quasi-substrate inhibitor of acetylcholinesterase.
D000098:Acetophenones / Q000494:pharmacology; D000110:Acetylcholinesterase / Q000097:blood; D000447:Aldehydes / Q000494:pharmacology*; D000818:Animals; D002800:Cholinesterase Inhibitors; D004305:Dose-Response Relationship, Drug; D004593:Electrophorus; D004912:Erythrocytes / Q000201:enzymology; D006801:Humans; D007531:Isoflurophate / Q000494:pharmacology; D007659:Ketones / Q000494:pharmacology*; D051379:Mice; D009132:Muscles / Q000201:enzymology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology
D000098:Acetophenones; D000447:Aldehydes; D002800:Cholinesterase Inhibitors; D007659:Ketones; D000644:Quaternary Ammonium Compounds; D007531:Isoflurophate; D000110:Acetylcholinesterase