Synthesis, Characterization and In-Vitro Reactivation Potency of a Series of Substituted Keto and Aldoximes as Acetylcholinesterase Reactivators

Abstract

Acetylcholinesterase enzyme (AChE) is rendered inactive by the phosphorylation or phosphorylation of its active site by very hazardous organophosphorus substances, such as nerve agents or organophosphate pesticides. Inhibition of AChE results in an increased amount of acetylcholine in the central and peripheral nervous system which causes excess release of nerve impulses and then uncontrolled actions occur known as Cholinergic Syndrome. We have prepared oximes for the reactivation of such inhibited enzymes. Oximes act as nucleophiles and reactivate enzymes by attacking the phosphoryl group of organophosphates that have inhibited the active site of AChE. Primarily, these aldoximes are represented by mono quaternary pralidoxime or more extended bis-quaternary compounds like trimedoxime, obidoxime, and H-oxime i.e. HI 6. The inhibition of acetylcholinesterase is contingent of structure of the inhibitors, whereas reactivation of inhibited acetylcholinesterase depends on both the chemical structure of reactivator and inhibitors utilized. No single AChE reactivator can sufficiently reactivate an inhibited enzyme due to the enormous diversity of AChE inhibitors, regardless of the inhibitor’s chemical structure. Our study aimed to discover more new reactivators against acetylcholinesterase inhibition activity. For this more bis-oxime structures than those seen in routinely utilized reactivators. Mono-oximes of 4-acetylpyridine, 4-formylpyridine, indole-3-carboxaldehyde, and vanillin have been prepared. Mono quaternary and bis-quaternary salts of 4-acetylpyridine oxime have also been synthesized by using 1,3-dibromopropane. Some other symmetrical and non-symmetrical bis-oximes were also prepared in this regard. All prepared samples have been characterized by FTIR, 1H NMR, CHN and UV-Vis analysis. Reactivation activity will be estimated in vitro acetyl cholinesterase inhibition activity in human blood and plasma.