Self-organizing molecular field analysis of 2,4-thiazolidinediones: A 3D-QSAR model for the development of human PTP1B inhibitors.
Thiazolidinediones (TZDs) have been recently developed to treat diabetic patients that can reverse insulin resistance by activation of gamma isoform of peroxisome proliferator-activated receptor (PPAR-gamma). Self-Organizing Molecular Field Analysis (SOMFA) has been performed on TZD scaffold having h-PTP1B inhibitory activities for the development and optimization of lead. The master grids obtained from SOMFA models indicated significant electrostatic and shape potential contributions. These can be mapped back onto structural features relating to the trends in activities of the molecules. The robustness of generated SOMFA models was evidenced by various statistical measures. Overall, the present SOMFA study investigated the indispensable structural features of substituted TZDs which can be exploited for further structural modifications in order to optimize h-PTP1B inhibitors.
Thareja
Suresh
S
University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160 014, India.
Aggarwal
Saurabh
S
Bhardwaj
T R
TR
Kumar
Manoj
M
D055808:Drug Discovery; D006801:Humans; D016018:Least-Squares Analysis; D008958:Models, Molecular; D008968:Molecular Conformation; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D021281:Quantitative Structure-Activity Relationship; D015203:Reproducibility of Results; D045162:Thiazolidinediones / Q000737:chemistry* / Q000494:pharmacology*
D045162:Thiazolidinediones; C500090:thiazolidine-2,4-dione; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1