Synthesis and Biological Activity of Piperine Derivatives as Potential Agonists.

INTRODUCTION

Peroxisome proliferator-activated receptor () plays a key role in glucose, which is a ligand-mediated transcription factor. The lipid homeostasis often serves as a pharmacological target for new drug discovery and development.

MATERIALS AND METHODS

In the research, we synthesized a series of piperine derivatives and then used a fluorescence polarization-based ligand screening assay to evaluate the agonistic activity of . Then, we cultured human normal hepatocytes, which were treated with 100μM compounds or . Then, the levels of gene were determined so as to show whether the compounds could activate or inhibit the expression of .

RESULTS

A total of 30 piperine derivatives were synthesized and evaluated. Compound was identified as a potential agonist with IC at 2.43 μM, which is 2 times more potent than the positive control rosiglitazone with IC at 5.61μM. The human hepatocytes cells were cultured and treated with compounds , or as described in the "Materials and Methods" section. We found that compounds and could activate by 11.8, 1.9 and 7.0 times compared with the "blank", with compound activation being the most significant. Molecular docking studies indicated that the piperine derivative stably interacts with the amino acid residues of the complex active site, which is consistent with the results of the in vitro ligand screening assay.