Screening for antidiabetic compounds from Goji berries: Identification of novel small molecule PPARγ activators

The identification of novel antidiabetic PPARγ agents with lesser toxicity profile is of interest since the current PPARγ agonists, glitazones display serious side effects including heart failure and edema. Goji berries are used in the traditional Chinese medicine for the treatment of diabetes mellitus and hypertension and sold in health food products in the western countries. The aim of our study is to identify new PPARγ agonists from Goji berries by in silico screening from Goji berries, a followed by in vitro testing. Crystal structures of PPARγ with both partial and full agonist were used for in silico screening for higher predictivity. The in silico screening approach led to the identification of several small molecule amides having the favorable conformation in both partial and full agonist PDB structures. Subsequently, 24 small molecule amides were synthesized and tested using in vitro luciferase reporter gene assay. Compounds CA-G-001, CA-G-008 and CA-010 showed selectivity to PPARγ vs. PPARα and good fold activation when compared the positive control, Rosiglitazone. The details of in silico, in vitro results and other data will be presented.