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

Mushtaq A. Tantray, Imran Khan, Hinna Hamid, Mohammad Sarwar Alam, Sadiq Umar, Yakub Ali, Kalicharan Sharma, Firasat Hussain

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11 Scopus citations

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 IC 50 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.

Original languageEnglish (US)
Pages (from-to)918-926
Number of pages9
JournalChemical Biology and Drug Design
Volume87
Issue number6
DOIs
StatePublished - Jun 1 2016

Keywords

  • click chemistry
  • glycogen synthase kinase-3
  • inflammation
  • oxazolo[4,5-b]pyridine-2-one
  • pro-inflammatory mediators

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