STUDY ON 3D-QSAR OF PPARγ AGONISTS WITH THIAZOLIDINEDIONE AND ARYLKETO-ACID MOIETIES
- VernacularTitle:噻唑烷二酮和芳酮酸类PPARγ激动剂三维定量构效关系研究
- Author:
Xiang YI
;
Zongru GUO
- Publication Type:Journal Article
- From:
Acta Pharmaceutica Sinica
2001;36(4):262-268
- CountryChina
- Language:Chinese
-
Abstract:
AIM To build a model of two series of PPARγ agonists thiazolidinedione and aryketo-acid derivatives using 3D-QSAR method, and to reveal the structural features affecting the binding activity to PPARγ, which relates to antihyperglycemic and antihyperlipidemic activity and has a potential application to the treatment of type II diabetes. METHODS and RESULTS 48 agonists with selective activity for PPARγ were analyzed using CoMFA. Based upon the active conformation of rosiglitazone (BRL) extracted from its complex with PPARγ all agonists were aligned. The model from CoMFA showed a high ability to explain and predict the activity of PPARγ agonists with cross-validation correlation coefficient R2=0.656, that of non-cross-validataion R2=0.982, F10，37=201.1, and SE=0.115. CONCLUSION The CoMFA contour map indicates that the steric fields mainly contribute to the binding effect, and especially a bulky group in the arylketo-acid series favors in the increase of affinity for PPARγ, as compared to the thiazolidinedione.
