Docking studies on PPARγ of novel α-phenoxy phenyl propionic acid derivatives as antidiabetic agents

PPAR (Peroxisome proliferated activated receptor) have been identified as potential targets of type II diabetes. Peroxisome proliferators-activated receptors (PPAR γ) are group of nuclear receptor proteins. They play essential role in the cellular metabolism of carbohydrates, lipids and proteins, cell differentiation and development. PPARs function as transcription factors regulating the expression of genes. A series of α-Phenoxy phenylpropionic acid derivatives were computationally designed and optimized with the AutoDock 4.0.1 to investigate the interactions between the target compounds and the amino acid residues of the PPARγ. In this study, the docking studies were done using auto dock between computationally designed α-Phenoxy phenylpropionic acid derivatives and PPAR γ receptor. The free energies of binding (Δ G) and inhibition constants (Ki) of the docked ligands were calculated by the Lamarckian Genetic Algorithm (LGA). These values suggested that the designed α-Phenoxy phenylpropionic acid derivatives are excellent promoters of PPAR γ. Computationally designed ligands were prefiltered for their drug like properties by lipinski’s rule. Lipinski's rule of five was calculated for all the eight ligand molecules that satisfy the 'rule-of-5' and it was found that all the ligand molecules satisfied the rule for potent inhibitors.

Author(s): R. Sivakumar, N. Lokesh, A. Rajashekhar, N. Ramu, P. Saikishore and R. Venkatanarayanan

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