Pharmacophore Modeling, Atom Based 3D-QSAR and Docking Studies of Protein Tyrosine Phosphatase 1B Inhibitors

Author(s): Priyanka Malla, Rajnish Kumar, Manoj Kumar

Journal Name: Letters in Drug Design & Discovery

Volume 10 , Issue 4 , 2013

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Inhibitors of Protein Tyrosine Phosphatase 1B (PTP 1B), a negative regulator of insulin signal transduction, have been explored as potential antidiabetic agents. In the present work a series of bromo-retrochalcones as PTP 1B inhibitors have been used for pharmacophore modeling, atom based 3D-QSAR and docking studies. A five-point pharmacophore with two hydrogen bond acceptors (A), two aromatic rings (R), and one hydrophobe (H) as pharmacophoric features was developed using PHASE. The pharmacophoric hypothesis was used to generate statistically significant 3DQSAR models. The best model showed good PLS statistics characterized by survival score (9.306), cross-validated r2 (Q2) (0.706), regression coefficient r2 (0.861), Pearson-R (0.853), and F value (76.4). Taken together, the Partial least square (PLS) generated 3D-QSAR pharmacophore and regression cubes along with structure based drug design provided a three dimensional topological view of the active site that can be used for the rational modification of bidentate PTP 1B inhibitors.

Keywords: Partial least square, Pharmacophore, PHASE, Docking, MM-GBSA, Structure based drug design

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Article Details

Year: 2013
Published on: 12 March, 2013
Page: [303 - 319]
Pages: 17
DOI: 10.2174/1570180811310040004
Price: $65

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