AccScience Publishing / ITPS / Volume 2 / Issue 1 / DOI: 10.26689/itps.v2i1.499
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RESEARCH ARTICLE

Schiff Base Oxime Derivatives Reactivate Chlorpyrifos-induced Acetylcholinesterase Inhibition

Manjunatha S. Katagi1 Jennifer Fernandes2 Shivalingrao Mamledesai3 M. L. Sujatha1 A. Rekha4 Girish Bolakatti5*
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1 Department of Pharmaceutical Chemistry, Bapuji Pharmacy College, Davangere, Karnataka, India
2 Department of Pharmaceutical Chemistry, N G S M Institute of Pharmaceutical Sciences, Mangalore, Karnataka, India
3 Department of Pharmaceutical Chemistry, PES’s Rajaram and Tarabai Bandekar College of Pharmacy, Farmagudi, Ponda, Goa, India
4 Department of International Public Health, 226 Grey St, South Bank Campus, Qld 4101, Griffith University, Brisbane, Australia
5 Department of Pharmaceutical Chemistry, GM Institute of Pharmaceutical Sciences and Research, Davangere, Karnataka, India
INNOSC Theranostics and Pharmacological Sciences 2019, 2(1), 499 https://doi.org/10.26689/itps.v2i1.499
Submitted: 10 December 2018 | Accepted: 14 June 2019 | Published: 2 July 2019
© 2019 by the Authors. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
Abstract

Background: The biological effects of organophosphorus 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 fulfill 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 in vitro reactivating potency against chlorpyrifos inhibited AChE.
Methods: The amino group of 4-amino acetophenone was 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 physical 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) showed 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%, 60 min) against chlorpyrifos-inhibited AChE.
Conclusion: Compounds having chloro (2a) and nitro (2d) substitution on the 4th position gave good activity against chlorpyrifosinhibited AChE. Moreover, these Schiff base oximes appear to be very promising due to their sufficient reactivation strength at lower concentration (10−3 M).

Keywords
Schiff base
oxime
acetylcholine
acetylcholinesterase
reactivation
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Conflict of interest
The authors declare no conflicts of interest.
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INNOSC Theranostics and Pharmacological Sciences, Electronic ISSN: 2705-0823 Published by AccScience Publishing