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

作　　者：Li Zhou Ye Zhong Meng-Zhu Xue Dong Kuang Xian-Wen Cao Zhen-Jiang Zhao Hong-Lin Li Yu-Fang Xu Rui Wang 

机构地区：[1]Shanghai Key Laboratory of New Drug Design,State Key Laboratory of Bioreactor Engineering,School of Pharmacy,East China University of Science and Technology

出　　处：《Chinese Chemical Letters》2015年第1期63-68,共6页中国化学快报（英文版）

基　　金：supported by the National Natural Science Foundation of China(Nos.81072627,81230090 and 81222046);Shanghai Committee of Science and Technology(Nos.12431900901 and 12401900801);the Fundamental Research Funds for the Central Universities(111 Project,No.B07023)

摘　　要：We designed and synthesized a series of 2-thioxo-4-thiazolidinone derivatives and evaluated them on peroxisome proliferator activated receptor γ（PPARγ） binding activities.Through the biological assays,compounds 18 and 38 were highlighted with K_i values of 12.15 nmol/Land 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 Rosightazone in the PPARγligand 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 PPARγ.We designed and synthesized a series of 2-thioxo-4-thiazolidinone derivatives and evaluated them on peroxisome proliferator activated receptor γ（PPARγ） binding activities.Through the biological assays,compounds 18 and 38 were highlighted with K_i values of 12.15 nmol/Land 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 Rosightazone in the PPARγligand 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 PPARγ.

关 键 词：2-Thioxo-4-thiazolidinone Peroxisome proliferator activated receptorγ Binding activities SAR Molecular docking 

分 类 号：TQ460.1[化学工程—制药化工]