Novel Piperine Derivatives with Antidiabetic Effect as PPAR-γ Agonists

Chem Biol Drug Des. 2016 Sep;88(3):354-62. doi: 10.1111/cbdd.12760. Epub 2016 May 27.


Piperine is an alkaloid responsible for the pungency of black pepper. In this study, piperine isolated from Piper nigrum L. was hydrolyzed under basic condition to obtain piperic acid and was used as precursor to carry out the synthesis of twenty piperine derivatives containing benzothiazole moiety. All the benzothiazole derivatives were evaluated for their antidiabetic potential by OGT test followed by assessment of active derivatives on STZ-induced diabetic model. It was observed that nine of twenty novel piperine analogues (5b, 6a-h), showed significantly higher antidiabetic activity in comparison with rosiglitazone (standard). Furthermore, these active derivatives were evaluated for their action as PPAR-γ agonists demonstrating their mechanism of action. The effects on body weight, lipid peroxidation, and hepatotoxicity after administration with active derivatives were also studied to further establish these derivatives as lead molecules for treatment of diabetes with lesser side-effects.

Keywords: PPAR-γ; amide linkage; antidiabetic; gene expression; piperine.

MeSH terms

  • Animals
  • Blood Glucose / analysis
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / genetics
  • Diabetes Mellitus, Experimental / metabolism
  • Gene Expression Regulation / drug effects
  • HEK293 Cells
  • Humans
  • Hypoglycemic Agents / chemistry*
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use*
  • Lipid Peroxidation / drug effects
  • Male
  • Molecular Docking Simulation
  • PPAR gamma / agonists*
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • Piper nigrum / chemistry
  • Piperidines / chemistry*
  • Piperidines / pharmacology
  • Piperidines / therapeutic use*
  • Rats, Wistar


  • Blood Glucose
  • Hypoglycemic Agents
  • PPAR gamma
  • Piperidines