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 5 h 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 to 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.

This article is protected by copyright. All rights reserved.

We synthesized series of novel oxazolo[4,5-b]pyridine-2-one based 1,2,3-triazoles.

Compounds were assessed for in vitro GSK-3β inhibition and in vivo anti-inflammatory activity.

Compounds 4g, 4d, 4f and 4i were most active against both GSK-3β and inflammation and also suppressed concentrations of NO, TNF-α, IL-1β and IL-6 ex vivo.

4g, 4d, 4f and 4i also didn't cause any gastric ulceration and could be promising for GSK-3β inhibition with potential for treatment of anti-inflammatory disorders.

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1PNiIlf
via IFTTT