Synthesis and Evaluation of Quinolin-2(1H)-One Fused Oxazole as an <i>In Vitro</i> Reactivator of Organophosphorus Compound Inhibited Acetylcholinesterase

Abstract

Background: Poisoning with organophosphorus (OP) compounds are frequent because OP are widely used as insecticide or pesticide. OP compounds exert inhibition on acetylcholinesterase (AChE) activity by irreversibly binding to the catalytic site of the enzyme. The inhibition of AChE leads to hyperstimulation of muscarnic and nicotinic receptors due to excess of acetylcholine (ACh). Methodology: Various quinolin-2(1H)-one fused oxazole were synthesized by condensation and cyclization of chalcones with hydroxylamine hydrochloride in presence of piperidine. Synthesized compound were tested for in vitro reactivation of chlorpyrifos and methyl parathion inhibited AChE enzyme using pralidoxime (2-PAM) as standard reference. Result: Among the synthesized compounds, the compound 3b, 3f, 3g, and 5a have showed promising activity as compared to standard against chlorpyrifos inhibited AChE. However, 3f and 3g showed good activity as compared to standard against methyl parathion inhibited AChE. th Conclusion: The derivatives having nitro and chloro substitution at 4 th position gave potent activity against both OP compounds as compared to standard at concentration 0.001 M. Moreover, these quinolone fused oxazole seem to be very promising because of their sufcient reactivation potency at lower concentration (10 -3 M).