Interaction of imidazolium and pyridinium dioximes with human erythrocyte acetylcholinesterase

Abstract

Two pyridinium and two imidazolium dioximes were tested as reversible inhibitors of human erythrocyte acetylcholinesterase (AChE), as protectors of the enzyme against phosphylation and as reactivators of the phosphylated AChE. All four dioximes reversibly inhibited AChE, protected the enzyme against phosphylation by soman and tabun and reactivated AChE after phosphylation by sarin, VX and tabun. From the experimental results the enzyme/dioxime dissociation constants were evaluated for the catalytically active enzyme and for phosphylated enzyme. The evaluation constants have shown that all four dioximes have about the same affinity for the catallytically active as for the phosphylated AChE. Obtained results also indicate that imidazolium dioximes probably bind only to the allosteric, while pyridinium dioximes bind to both, the catalytic and the allosteric site of the enzyme.