Computer-aided discovery, validation, and mechanistic characterization of novel neolignan activators of peroxisome proliferator-activated receptor gamma.

ABSTRACT: Peroxisome proliferator-activated receptor gamma (PPAR gamma) agonists are used for the treatment of type 2 diabetes and metabolic syndrome. However, the currently used PPAR gamma agonists display serious side effects, which has led to a great interest in the discovery of novel ligands with favorable properties. The aim of our study was to identify new PPARgamma agonists by a PPAR gamma pharmacophore-based virtual screening of 3D natural product libraries. This in silico approach led to the identification of several neolignans predicted to bind the receptor ligand binding domain (LBD). To confirm this prediction, the neolignans dieugenol, tetrahydrodieugenol, and magnolol were isolated from the respective natural source or synthesized and subsequently tested for PPAR gamma receptor binding

SUBMITTER: Fakhrudin N 

PROVIDER: S-EPMC3523390 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature