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Letters in Drug Design & Discovery

Editor-in-Chief

ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

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

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

Volume 10, Issue 4, 2013

Page: [303 - 319] Pages: 17

DOI: 10.2174/1570180811310040004

Price: $65

Abstract

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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