Manjunatha S. Katagi 1*, Jennifer Fernandes 2, Shivlingrao Mamledesai 3, D. Satyanarayana 2, Prakash Dabadi 4, Girish Bolakatti 4
- Bapuji Pharmacy College, S.S. Layout, Davangere - 577 004, Karnataka, India
- Department of Pharmaceutical Chemistry, N G S M Institute of Pharmaceutical Sciences, Mangalore 574 160, Karnataka, India
- Department of Pharmaceutical Chemistry, PES's Rajaram & Tarabai Bandekar College of Pharmacy, Farmagudi-Ponda, 403 401, Goa, India
- Bapuji Pharmacy College, S.S.Layout, Davangere - 577 004, Karnataka, India
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 4th 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).
References
- Musilek K, Kuka K, Jun D, Dohnal V, Dolezal M. Synthesis of novel series of bispyridinium compounds bearing (E)-but-2-ene linker and evaluation of their reactivation activity against chlorpyrifos-inhibited acetylcholinesterase. Bioorg Med Chem Lett 2006;16:622-7.
- Vijaya kumar S, Fareedullah Md, Sudhakar Y, Venkateswarlu, Kumar EA Current review on organophosphorus poisoning. Scholars research library2010;2(4):199-215.
- TripathiKD Essential of medical pharmacology. Jaypee brothers medical publishers, Mumbai. 2008.
- Patocka J, Cabal J, Kuka K, Jun D. Oxime reactivation of acetylcholinesterase inhibited by toxic phosphorus esters: in vitro kinetics and thermodynamics. JApplBiomed2005;3:91-9.
- Taylor P, Radic Z, Hosca NA, Camp S, Marchot P, Berman HA. Structural basis for the specificity of cholinesterase catalysis and inhibition. Toxicol Lett1995;82�83:453�8.
- Patrick GL. An introduction to medicinal chemistry. Oxford University, New York. 2006.
- Worek F, Mast U, Kiderlen D, Diepold C, Eyer P. Improved determination of acetylcholinesterase activity in human whole blood. Clinica Chemica Acta 1999;288:73�90.
- Thunga G, Sam KG, Khera K, Pandey S, Sagar SV. Evaluation of incidence, clinical characteristics and management in organophosphorous poisoning patients in a tertiary care hospital. J Toxicol Environ HealthSci2010;2(5):73-6.
- Kassa J, Kuca K, Cabal J. A comparison of the potency of trimedoxime and other currently available oximes to reactivate tabun-inhibited acetylcholinesterase and eliminate acute toxic effects of tabun. Biomed Pap 2005; 149(2): 419�23.
- Musilek K, Kuca K, Jun D, Dolezal M. Progress in Synthesis of new acetylcholin esterase reactivators during the period 1990-2004. Curr Org Chem 2007;11(2):229�38.
- Katagi MS, Bolakatti G, Badiger A, Satyanarayana D, Mamledesai SN, Sujatha ML. Synthesis, spectral characterization and antimicrobial activity of substituted thiazolyl derivatives of 2-quinolone. Drug Res 2013; 63:53-9.
- Ginsburg S, Wilson IB. Oximes of the pyridine series. JAmChemSoc1957; 79P:481�5.
- Ellman GL, Courtney DK, Andres V, Feartherstone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 1961;7:88�93.
