Schiff Base Oxime Derivatives Reactivate Chlorpyrifos-induced Acetylcholinesterase Inhibition

Abstract

Background: The biological effects of organophosphorus (OP) compounds are connected with the irreversible inhibition of acetylcholinesterase (AChE), an important neuromediator acetylcholine (ACh) splitting enzyme in the human body at the synaptic clefts. Due to this inhibition, AChE is unable to fulfil its physiological function resulting in the accumulation of ACh, which, in turn over stimulates the parasympathetic nerve receptors, and causes fatal cholinergic crisis.
 Objective: The objective of the study was to synthesize a series of Schiff base oximes and to assess their evaluating for their in vitro reactivating potency against chlorpyrifos inhibited AChE.
 Methods: The amino group of 4-amino acetophenone exploited by treating with substituted benzaldehyde in the presence of glacial acetic acid to form Schiff base (1a-1f). The titled compounds (2a-2f) were prepared by treating Schiff base with hydroxylamine hydrochloride in the presence of alcohol. Through structural and spectral analysis, the structure of compounds was confirmed. The synthesized compounds were evaluated for their reactivation efficacy against chlorpyrifos-inhibited rat brain AChE by Ellman's method.
 Results: The pralidoxime (2-PAM) was potent reactivation against chlorpyrifos-inhibited AChE at the concentration tested (0.001 M). In this case, the compounds 2a (40.4%, 60 min) and 2d (37.9%, 60 min) showed promising reactivation as compared to 2-PAM (40.6%, 60min) against chlorpyrifos-inhibited AChE.
 Conclusion: Compounds having chloro (2a) and nitro (2d) substitution on 4th position gave good activity against chlorpyrifos-inhibited AChE. Moreover, these Schiff base oximes seem to be very promising because of their sufficient reactivation strength at lower concentration (10-3 M).

Approaches in Theranostics and Pharmacological Sciences

“…Authors used the formulations from natural polymers/gums and have shown a promising delivery system which can enhance the bioavailability and has potential for greater therapeutic efficacy. The second article by Katagi et al worked on "Schiff Base Oxime Derivatives Reactivate Chlorpyrifos-induced Acetylcholinesterase Inhibition" [2]. This study is primarily aimed at synthesizing a series of Schiff base oximes and assessing the in vitro reactivating potency against chlorpyrifosinhibited acetylcholinesterase.…”