Inhibition of acetylcholinesterase by 14 achiral and five chiral imidazole derivates

Homological series of 14 achiral derivates and series of five chiral derivates of imidazole were tested in vitro as inhibitors of hydrolysis of acetylcholine using enzyme preparation of acetylcholinesterase from electric eel. The batch stirred reactor at 25 °C, pH 8 (phosphate buffer), ionic strength 0.11 M and catalytic activity of the enzyme preparation 0.14 U ml−1 of the reaction mixture were used. The temporal dependences of actual concentrations of acetylcholine, choline and acetic acid were determined by an original HPLC method. For all used inhibitors, these time dependences conform with the probability of more than 90% to the model of competitive irreversible inhibition. All kinetic constants including k3 defining the rate of inhibition (0.38–5.3 M−1 s−1) and qualified estimation of the absolute acetylcholinesterase concentration in the reaction mixture (40–110 nM) were determined.