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.
