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
Letters in Drug Design & Discovery
Title:Pharmacophore Modeling, Atom Based 3D-QSAR and Docking Studies of Protein Tyrosine Phosphatase 1B Inhibitors
Volume: 10 Issue: 4
Author(s): Priyanka Malla, Rajnish Kumar and Manoj Kumar
Affiliation:
Keywords: Partial least square, Pharmacophore, PHASE, Docking, MM-GBSA, Structure based drug design
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.
Export Options
About this article
Cite this article as:
Malla Priyanka, Kumar Rajnish and Kumar Manoj, Pharmacophore Modeling, Atom Based 3D-QSAR and Docking Studies of Protein Tyrosine Phosphatase 1B Inhibitors, Letters in Drug Design & Discovery 2013; 10 (4) . https://dx.doi.org/10.2174/1570180811310040004
DOI https://dx.doi.org/10.2174/1570180811310040004 |
Print ISSN 1570-1808 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-628X |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Patent Selections
Recent Patents on Inflammation & Allergy Drug Discovery Gestational Diabetes Mellitus: Post-partum Risk and Follow Up
Reviews on Recent Clinical Trials Risk Factors for Development of Heart Failure
Current Cardiology Reviews A Systematic Review of the Uterine Relaxant Effect of Herbal Sources
Current Pharmaceutical Biotechnology The Role of Platelets in Athero-Thrombotic Events
Current Pharmaceutical Design Spirolactones: Recent Advances in Natural Products, Bioactive Compounds and Synthetic Strategies
Current Medicinal Chemistry Antihypertensive Therapy in Children: Differences in Medical Approach Between the United States and Europe
Current Medicinal Chemistry Disintegrins from Snake Venoms and their Applications in Cancer Research and Therapy
Current Protein & Peptide Science Common Cellular and Molecular Mechanisms Underlying Alzheimer’s Disease and Type 2 Diabetes: A Knowledge-Driven Approach
CNS & Neurological Disorders - Drug Targets TRAIL-Based Therapeutic Approaches for the Treatment of Pediatric Malignancies
Current Medicinal Chemistry Pharmacological Interactions of Paraoxonase 1 (PON1): A HDL-Bound Antiatherogenic Enzyme
Current Clinical Pharmacology Mind-Body Therapies and Osteoarthritis of the Knee
Current Rheumatology Reviews Circulating Meteorin-like Levels in Patients with Type 2 Diabetes Mellitus: A Meta-Analysis
Current Pharmaceutical Design Anthropometric Correlation with Metabolic Syndrome in Sarajevo Population
Endocrine, Metabolic & Immune Disorders - Drug Targets Medicinal Agents and Metabolic Syndrome
Current Medicinal Chemistry Beneficial Effects of Corn Silk on Metabolic Syndrome
Current Pharmaceutical Design Whole Embryo Culture: An Important Tool in Developmental Toxicology Today
Current Pharmaceutical Design Dietary Toxins, Endoplasmic Reticulum (ER) Stress and Diabetes
Current Diabetes Reviews Atrial Fibrillation: The Emerging Role of Inflammation and Oxidative Stress
Cardiovascular & Hematological Disorders-Drug Targets The Effects of Herbal Medicines on Women Sexual Dysfunction: A Systematic Review
Current Drug Discovery Technologies