Activities of Tetramethylene-Bis-Onium Reversible Cholinesterase Inhibitors as Influenced by the Nature of the Onium Atom

Abstract

Inorganic tetramethylene bis-onium compounds were studied as reversible inhibitors of various cholinesterases (ChE), i.e., human erythrocyte acetyl-ChE, horse blood serum butyryl-ChE, grass frog Rana temporaria brain ChE, and Pacific squid Todarodes pacificus and commander squid Berryteuthis magister visual ganglia ChE from various habitats in the northwest Pacific Ocean, in order to study the influence of the nature of the onium atom on their anti-ChE activities. bis-Phosphonium inhibitors turned out to be significantly more potent effectors than bis-ammonium compounds, which may actually have been due to the significant increases of size and hydrophobicity of the onium groups. The bis-ammonium organosilicon compound and its monoammonium analog turned out to be equally active as reversible ChE inhibitors in mammals. The bis-phenyliodonium derivative was studied for the first 7time, was characterized by significantly increased hydrophobicity due to introduction of F atoms into the tetramethylene spacer in the onium chain, and exhibited marked anti-ChE activity with respect to mammalian ChE.