Discovery of novel thiazole derivatives containing pyrazole scaffold as PPAR-γ Agonists, α-Glucosidase, α-Amylase and COX-2 inhibitors; Design, synthesis and in silico study

Compounds 16b, 16c, 16e, and 16k demonstrated 72-79% PPAR-γ activation, comparable to the reference drug rosiglitazone (74%).

• All tested thiazole derivatives showed varying degrees of anti-diabetic activity in vitro and in vivo.
• The derivatives 16b, 16c, 16e, and 16k exhibited the highest inhibitory activities against α-glucosidase and α-amylase, with IC values ranging from 0.128 to 0.314 μM and 7.74 to 35.85 μM, respectively.
• In vivo studies indicated that compounds 16b, 16c, 16e, and 16k had good hypoglycemic effects that were comparable to rosiglitazone.
• Compounds 16b and 16c showed superior COX-2 selectivity with selectivity indices of 18.7 and 31.7, respectively, compared to celecoxib's index of 10.3.
• The in vivo anti-inflammatory activity of derivatives 16b and 16c was more potent than celecoxib, with effective doses of 8.2 and 24 mg/kg versus 30 mg/kg for celecoxib.

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