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
-
Folate Nutrigenetics: A Convergence of Dietary Folate Metabolism, Folic Acid Supplementation, and Folate Antagonist Pharmacogenetics
Drug Metabolism Letters Adipose-Derived Factors During Nutritional Transitions
Current Nutrition & Food Science Nanoparticles as Alternative Strategies for Drug Delivery to the Alzheimer Brain: Electron Microscopy Ultrastructural Analysis
CNS & Neurological Disorders - Drug Targets Antidiabetic Effect of Polyphenolic Extracts from Selected Edible Plants as α-Amylase, α -Glucosidase and PTP1B Inhibitors, and β Pancreatic Cells Cytoprotective Agents - A Comparative Study
Current Topics in Medicinal Chemistry Renal Innervation in Resistant Hypertension: A Review of Pathophysiology and Renal Denervation as Potential Treatment
Current Hypertension Reviews Lipids, Statins and Heart Failure: An Update
Current Pharmaceutical Design The Worrying Trend of Diabetes Mellitus in Saudi Arabia: An Urgent Call to Action
Current Diabetes Reviews Renal Phosphate Handling in Antiretroviral-naive HIV-Infected Patients
Infectious Disorders - Drug Targets Plasma Ghrelin Levels in Patients with Familial Mediterranean Fever
Protein & Peptide Letters Overcoming Barriers to Evidence-Based Diabetes Care
Current Diabetes Reviews Aspartic Protease Inhibitors as Potential Anti-Candida albicans Drugs: Impacts on Fungal Biology, Virulence and Pathogenesis
Current Medicinal Chemistry Ex Vivo Gene Transfer for Improvement of Transplanted Pancreatic Islet Viability and Function
Current Pharmaceutical Design The Role of Parathyroid Hormone-Related Protein (PTHrP) in the Pathophysiology of Diabetes Mellitus
Mini-Reviews in Medicinal Chemistry Insulin Resistance and Postprandial Hyperglycemia the Bad Companions in Natural History of Diabetes: Effects on Health of Vascular Tree
Current Diabetes Reviews Potential Application of Induced Pluripotent Stem Cells in Cell Replacement Therapy for Parkinsons Disease
CNS & Neurological Disorders - Drug Targets Editorial: Cardiovascular Disease Mortality Rates are Plateauing in Certain Age Groups and Regions. Can we Keep them Declining?
Current Vascular Pharmacology Mass Spectrometry: An Emerging Alternative to Traditional Methods for Measurement of Diagnostic Proteins, Peptides and Amino Acids
Current Protein & Peptide Science Whole Milk and Full-Fat Dairy Products and Hypertensive Risks
Current Hypertension Reviews Myocardial Revascularization for the Elderly: Current Options, Role of Off-pump Coronary Artery Bypass Grafting and Outcomes
Current Cardiology Reviews Steered Molecular Dynamics-A Promising Tool for Drug Design
Current Bioinformatics