Design, synthesis and evaluation of PPAR gamma binding activity of 2-thioxo-4-thiazolidinone derivatives

We designed and synthesized a series of 2-thioxo-4-thiazolidinone derivatives and evaluated them on peroxisome proliferator activated receptor gamma (PPAR gamma) binding activities. Through the biological assays, compounds 18 and 38 were highlighted with K-i values of 12.15 nmol/L and 14.46 nmol/L, respectively. Then structure-activity relationship (SAR) was analyzed to screen privileged structural modifications. Moreover, molecular fitting of these compounds onto the approved drug Rosiglitazone in the PPAR gamma ligand binding domain was performed to elucidate the SAR and explore potential receptor-ligand interactions. These results demonstrate that the 2-thioxo-4-thiazolidinones can be considered as new promising molecular probes with excellent binding activities to PPAR gamma. (C) 2014 Rui Wang and Yu-Fang Xu. Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. All rights reserved.