engleski

Inhibition of acetylcholinesterase by N-methylpyridinium derivatives

1-N-methylpyridinium iodide (I) and its three derivatives: 2-(hydroxyiminomethyl)-1-methylpyridinium iodide (2-PAM), 3-(hydroxy)-2-(hydroxyiminomethyl)-1-methylpiridinium iodide (II) and the dimethylcarbamate of compound II (III) were assayed for their inhibitory effect in vitro on the human blood acetylcholinesterase (EC 3.1.1.7, AChE). Compounds II and III were newly synthetized oximes. The enzyme activity was measured spectrophotometrically with substrate acetylthiocholine (ATCh) in the presence of the DTNB reagent, in 0.1 M phosphate buffer of pH 7.4. Compounds I, 2-PAM and II were reversible inhibitors of AChE. The dissociation constants of the enzyme/inhibitor complex for binding in the AChE catalytic site were evaluated from the relationships of the apparent dissociation constants vs low ATCh concentrations (up to 1.0 mM) and their values were between 0.3 and 1.9 mM. Compound I was found to bind also at the allosteric AChE binding site and the dissociation constant evaluated at high ATCh concentrations (1.0 to 10 mM) was 0.6 mM. Compound III was also a week AChE acylating inhibitor.

pyridinium compounds; 2-PAM; oximes; acetylcholinestrase inhibition

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