Tetramethonium derivatives as reversible inhibitors of various cholinesterases

Abstract

To study the effect of the onium atom nature on anticholinesterase efficiency, we tested elementorganic derivatives of tetramethylenbisonium compounds as reversible inhibitors of the following cholinesterases (ChE): acetyl-ChE from human erythrocytes, butyryl-ChE from horse serum, ChE from the brain of the grass frog Rana temporaria, ChEs from visual ganglia of the Pacific squid Todarodes pacificus, and ChE from visual ganglia of the commander squid Berryteuthis magister from different habitats in the Northwestern Pacific Ocean. Bisphosphonium inhibitors were found to be much stronger effectors than bisammonum compounds, although this may be due to a significantly increased size and hydrophobicity of their onium groups. Bisammonium organosilicon compound and its monoammonium analog were equally active as reversible ChE inhibitors in mammals. The first studied bis(phenyliodonium) derivative, which is characterized by a significantly increased hydrophobicity due to the introduction of fluorine atoms to the interonium tetramethylene chain, also exhibited a pronounced anticholinesterase effect on mammalian ChE.