The effect of substituted thiophene and benzothiophene derivates on PPARγ expression and glucose metabolism

Abstract

Eighteen substituted thiophene and benzothiophene derivatives were studied for their effects on peroxisome proliferator-activated receptor γ (PPARγ) in HepG2 cells. Three derivatives (compounds 5, 120.97%; 15, 102.14%; and 17, 113.82%) were found to transactivate PPARγ in vitro. By comparison, the positive control rosiglitazone (Ros) transactivated PPARγ by 311.53%. The three compounds were studied for their effects on glucose metabolism in vivo in KK/Ay diabetic mice. In vivo, the 2-(β-carbonyl/sulfonyl) butyryl-thiophene compounds 5 and 15 significantly decreased blood glucose levels (compounds 5, to < 15.6 mmol/L; 15, to < 10 mmol/L), improved glucose tolerance, improved impaired pancreatic islet β-cells, and lowered serum insulin levels.

Keywords::

• Peroxisome proliferator-activated receptor γ
• antidiabetic drugs
• 2-(β-carbonyl/sulfonyl) butyryl-thiophene derivatives
• KK/Ay diabetic mice

Acknowledgments

The project was supported by the National Nature Science Foundation of the P. R. China (Grant 30772646, 30671110) and in part by grants from the China National “973” program (2006CB503901), and the National Infrastructure Program of Chinese Genetic Resources (2006DKA21301).