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Synthesis of Novel Oxazolo[4,5‐b]pyridine‐2‐one based 1,2,3‐triazoles as Glycogen Synthase Kinase‐3 β Inhibitors with Anti‐inflammatory Potential
Author(s) -
Tantray Mushtaq A.,
Khan Imran,
Hamid Hinna,
Alam Mohammad Sarwar,
Umar Sadiq,
Ali Yakub,
Sharma Kalicharan,
Hussain Firasat
Publication year - 2016
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12724
Subject(s) - in vivo , gsk 3 , ic50 , pharmacology , chemistry , anti inflammatory , glycogen synthase , in vitro , inflammation , edema , carrageenan , histopathology , kinase , biochemistry , enzyme , medicine , biology , pathology , immunology , microbiology and biotechnology
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 ‐3 β inhibitory activity. Compound 4g showed maximum inhibition with IC 50 value of 0.19 μ m . Keeping in view the effect of GSK ‐3 β inhibition on inflammation, compounds 4g , 4d , 4f , 4i , 4n and 4q exhibiting significant GSK ‐3 β 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 ‐1 β , and IL ‐6 substantially in comparison with indomethacin, an anti‐inflammatory drug as well as SB 216763, a GSK ‐3 β inhibitor, reported to exert a similar effect. Histopathology studies confirmed the tolerance of gastric mucosa to these compounds.