TY - JOUR
T1 - 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
AU - Tantray, Mushtaq A.
AU - Khan, Imran
AU - Hamid, Hinna
AU - Alam, Mohammad Sarwar
AU - Umar, Sadiq
AU - Ali, Yakub
AU - Sharma, Kalicharan
AU - Hussain, Firasat
N1 - Publisher Copyright:
© 2016 John Wiley & Sons A/S.
PY - 2016/6/1
Y1 - 2016/6/1
N2 - 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.
AB - 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.
KW - click chemistry
KW - glycogen synthase kinase-3
KW - inflammation
KW - oxazolo[4,5-b]pyridine-2-one
KW - pro-inflammatory mediators
UR - https://www.scopus.com/pages/publications/84958643574
UR - https://www.scopus.com/pages/publications/84958643574#tab=citedBy
U2 - 10.1111/cbdd.12724
DO - 10.1111/cbdd.12724
M3 - Article
C2 - 26804375
AN - SCOPUS:84958643574
SN - 1747-0277
VL - 87
SP - 918
EP - 926
JO - Chemical Biology and Drug Design
JF - Chemical Biology and Drug Design
IS - 6
ER -
