title: Synthesis of Novel Oxazolo[4,5-b]pyridine-2-one based 1,2,3-triazoles as Glycogen Synthase Kinase-3β Inhibitors with Anti-inflammatory Potential.
abstract: A novel series of oxazolo[4,5-b]pyridine-2-one based 1,2,3-triazoles has been synthesized by click chemistry approach and evaluated for in vitro GSK-3β inhibitory activity. Compound 4g showed maximum inhibition with IC50 value of 0.19 μm. Keeping in view the effect of GSK-3β inhibition on inflammation, compounds 4g, 4d, 4f, 4i, 4n and 4q exhibiting significant GSK-3β inhibition were examined for in vivo anti-inflammatory activity in rat paw edema model. The compounds 4g, 4d, 4f and 4i showed pronounced in vivo anti-inflammatory activity (76.36, 74.54, 72.72 and 70.90%, respectively, after 5h post-carrageenan administration) and were further found to inhibit the pro-inflammatory mediators, viz. NO, TNF-α, IL-1β, and IL-6 substantially in comparison with indomethacin, an anti-inflammatory drug as well as SB216763, a GSK-3β inhibitor, reported to exert a similar effect. Histopathology studies confirmed the tolerance of gastric mucosa to these compounds.
authors.affiliation: Department of Chemistry, Faculty of Science, Hamdard University (Jamia Hamdard), New Delhi, 110 062, India.
authors.forename: Mushtaq A
authors.initials: MA
authors.lastname: Tantray
authors.affiliation: Department of Chemistry, Faculty of Science, Hamdard University (Jamia Hamdard), New Delhi, 110 062, India.
authors.forename: Imran
authors.initials: I
authors.lastname: Khan
authors.affiliation: Department of Chemistry, Faculty of Science, Hamdard University (Jamia Hamdard), New Delhi, 110 062, India.
authors.forename: Hinna
authors.initials: H
authors.lastname: Hamid
authors.affiliation: Department of Chemistry, Faculty of Science, Hamdard University (Jamia Hamdard), New Delhi, 110 062, India.
authors.forename: Mohammad Sarwar
authors.initials: MS
authors.lastname: Alam
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, WA, 99202, USA.
authors.forename: Sadiq
authors.initials: S
authors.lastname: Umar
authors.affiliation: Department of Chemistry, Faculty of Science, Hamdard University (Jamia Hamdard), New Delhi, 110 062, India.
authors.forename: Yakub
authors.initials: Y
authors.lastname: Ali
authors.affiliation: Drug Design and Medicinal Chemistry Lab, Department of Pharmaceutical Chemistry, Hamdard University (Jamia Hamdard), New Delhi, 110 062, India.
authors.forename: Kalicharan
authors.initials: K
authors.lastname: Sharma
authors.affiliation: Department of Chemistry, University of Delhi, New Delhi, 110 007, India.
authors.forename: Firasat
authors.initials: F
authors.lastname: Hussain
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D004487:Edema / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D000071679:Glycogen Synthase Kinase 3 beta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004791:Enzyme Inhibitors; D014230:Triazoles; D009569:Nitric Oxide; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat
keywords: click chemistry; glycogen synthase kinase-3; inflammation; oxazolo[4,5-b]pyridine-2-one; pro-inflammatory mediators