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

Manjunatha S. Katagi, Jennifer Fernandes, Shivlingrao Mamledesai, D. Satyanarayana, Prakash Dabadi, Girish Bolakatti
2015 Journal of Pharmaceutical Research  
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
more » ... mine 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 3gshowed good activity as compared to standard against methyl parathion inhibited AChE. th Conclusion: The derivatives having nitro and chloro substitution at 4 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 -3 (10 M). hydrolyzing the acetylcholine (ACh) neurotransmitter at 5 central and peripheral synapses. ACh accumulation results in an over-stimulation of cholinergic receptors, depending on the type and dose of the incorporated OP, causes disturbance of numerous body functions and 6 nally in respiratory arrest and death. Poisoning is the common method of suicide, especially in developing world. OP pesticide self-poisoning is estimated to kill around 200,000 people each year and mortality rate 7 varies from 10-20%.
doi:10.18579/jpcrkc/2015/14/2/79084 fatcat:oydu7qiosvd2ppfqlypegcov6m