Schiff Base Oxime Derivatives Reactivate Chlorpyrifos-induced Acetylcholinesterase Inhibition
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).
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