Benzothiazoles as effective inhibitors of cholinesterases: Kinetics and mechanism of inhibition

Abstract

The aim of our study was to determine the inhibition efficiency of the benzothiazoles tested, representing potential inhibitors of cholinesterases. (Reaction) kinetics of hydrolyses of acetylcholine and acetylthiocholine, uninhibited and inhibited by two types of enzyme, acetylcholinesterase, and butyrylcholinesterase, has been studied. Two methods for the determination of enzymatic hydrolysis were used, Ellman’s and pH-stat method and, totally, twelve inhibitors (benzothiazoles) selected to study the inhibited hydrolysis. The kinetic parameters of uninhibited and inhibited hydrolyses have been determined and, based on our current results of inhibition rate constant, 2,2,3,3- tetrafluoropropyl (S)-1-[(R)-1-(6-fluorobenzo[d]thiazole)ethyl-carbamoyl-2-methylpropylcarbamate found to be the best inhibitor of cholinesterases from the palette of the inhibiting substances tested.