NOVEL DRUG DISCOVERY FOR DIABETES TYPE-2 BY PHARMACOPHORE, VERTUAL SCREENING AND DOCKING OF PPARγ
Keywords:
PPARy, ZINC database, Schrodinger, PDBAbstract
Diabetes mellitus (DM) is a metabolic syndrome that constitutes a major health problem most drugs currently employed in the treatment of type 2 diabetes targeting the peroxisome proliferator-activated receptor (PPARγ) improving increasing prevalence of metabolic disorders, such as type 2. The 3 PPAR isoforms (alpha, delta/beta and gamma) are known to control many physiological functions including glucose absorption, lipid balance, and cell growth and differentiation. The peroxisome proliferator-activated receptors (PPARs) are involved in the regulation of lipid and glucose metabolism. Peroxisome proliferator-activated receptor gamma (PPARγ) has become an attractive molecular target for drugs that aim to treat diabetes mellitus type 2, and its therapeutic potency against skin cancer and other skin diseases is also currently being explored.
We have developed a virtual screening procedure based on ligand-based pharmacophore construction based on known drugs of type 2 diabetes and protein-ligand docking to discover novel scaffolds of (PPARγ) partial agonists. A dataset consisting of approximately 5,00,000 small molecule natural compounds were downloaded in (SDF) format from ZINC database. It was used as an input in the Generate phase database panel of phase. The structures were cleaned and different conformations were generated for each compound along with defining the pharmacophore sites points for each. The database prepared was then used to screen potential diabetes mellitus type 2. Structure and ligand based approach of drug designing is used for analysis for that some inhibitor molecules have been taken for docking by using the software GLIDE (Grid-based Ligand Docking with Energetics), run under Schrodinger’s Job Control facility by taken known protein structure from PDB (1NYX) .The predicted inhibitors are quite novel compared with the Known (PPARγ) inhibitor. The work provides insight for molecular understanding of (PPARγ) and can be used for development of anti-diabetes drugs.
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