title: [Study on 3D-QSAR of PPAR gamma agonists with thiazolidinedione and arylketo-acid moieties].
abstract: OBJECTIVE
  To build a model of two series of PPAR gamma agonists--thiazolidinedione and aryketo-acid derivatives using 3D-QSAR method, and to reveal the structural features affecting the binding activity to PPAR gamma, which relates to antihyperglycemic and antihyperlipidemic activity and has a potential application to the treatment of type II diabetes.
  
  
  RESULTS
  48 agonists with selective activity for PPAR gamma were analyzed using CoMFA. Based upon the active conformation of rosiglitazone (BRL) extracted from its complex with PPAR gamma all agonists were aligned. The model from CoMFA showed a high ability to explain and predict the activity of PPAR gamma agonists with cross-validation correlation coefficient R2 = 0.656, that of non-cross-validation R2 = 0.982, F10,37 = 201.1, and SE = 0.115.
  
  
  CONCLUSIONS
  The CoMFA contour map indicates that the steric fields mainly contribute to the binding effect, and especially a bulk group in the arylketo-acid series favors in the increase of affinity for PPAR gamma, as compared to the thiazolidinedione.
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China.
authors.forename: X
authors.initials: X
authors.lastname: Yi
authors.forename: Z R
authors.initials: ZR
authors.lastname: Guo
mesh_terms: D001577:Benzophenones / Q000737:chemistry*; D008968:Molecular Conformation; D015394:Molecular Structure; D010666:Phenylpropionates / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000737:chemistry; D013844:Thiazoles / Q000737:chemistry*; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000819:agonists* / Q000737:chemistry
chemical_list: D001577:Benzophenones; D010666:Phenylpropionates; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; C089946:2,4-thiazolidinedione