engleski

Synthesis of quinuclidine-imidazole derivatives and their interaction with acetylcholinesterase

Three compounds: N-methyl 3-oxo quinuclidinium iodide (I), 2-hydroxyiminomethyl 1, 3-dimethylimidazolium iodide (II) and this two compounds linked by a threemethylene link (III) were synthetised and studied as reversible inhibitors of human erythrocyte acetylcholinesterase (AChE) and as protectors against phosphorylation of the enzyme by the warfare agents Soman and VX. All the three compounds were found to be reversible inhibitors of AChE. The substrate was acetylthiocholine. The enzyme/inhibitor dissociation constants for the catalytic site were evaluated at low substrate concentrations up to 1.0 mM ; the compound II showed the highest affinity. At substrate concentrations above 1 mM inhibition by compound I revealed a second binding site. Inhibition at high substrate concentrations by the compounds II and III could not be measured due to a non-enzymic hydrolysis of the substrate by the oxime. All three compounds protected AChE against phosphorylation by soman and VX. Protection by compound I was enhanced through interaction of this compound with the allosteric binding site.

quinuclidine compounds; acetylcholinesterase; reversible inhibition; protection in phosphorylation; VX; soman

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