Understanding allosteric modulation of pparγ receptors by comparative qsar and molecular docking analysis

Abstract

Diabetes mellitus is a metabolic disorder of high incidence, according to th World Health Organization (WHO), it is predicted that 366 million individual worldwide will suffer from diabetes by 2030 (in which cases percentage o type 2 diabetes is 90%) Morbidity and mortality of these patients is due to macrovascular and microvascular complications. This alarming situatio becomes a challenge of scientists and researchers to design of new non hiazolidione derivative molecules to the preventing diabetes and it complications caused by other antidiabetic molecules. Peroxisome proliferator-activated gamma receptor (PPARand#947;) has been focused on my research because of the ligands for this receptor has emerged as potent insulin sensitizers that used as a major regulator of glucose homeostasis and adipogenesis and insulin resistance i.e. the major cause of type 2 diabetes concerned with the accumulation circulating free fatty acids in non-adipose tissue. Therefore to design a new molecule of non-thiazolidione derivative of peroxisome proliferator-activated receptor gamma (PPARand#947;) agonist by bioinformatics tool like QSAR and molecular docking studies were performed.Quantitative structure activity relationship (QSAR) analysis was carried out of different series of PPARand#947; agonist and on the basis of QSAR results seven new molecules were proposed. In order to ascertain the interaction of the proposed molecules with the residues of the target receptor (PPARand#947;) and the predict their binding affinity, a series of docking and scoring experiment were performed. On the basis of such studies it was found that only 7p molecule should show more potency compared to other molecules which were proposed on the basis of QSAR results, after that 7p molecule was synthesized and evaluated their hypoglycemic activity.