Abstract
The elevated level of dual-specificity tyrosine phosphorylation-regulated kinase 1A (Dyrk1A) is associated with the pathology of neurodegenerative diseases and has been implicated in some neurobiological alterations of Down syndrome, such as mental retardation. In the present article, a pharmacophore based 3D-QSAR model was developed for a series of leucettines possessing Dyrk1A inhibitory activity. The crucial molecular features observed in the developed pharmacophore model that account for binding affinity of ligands with the enzyme, include three H-bond acceptors (A), one positive ionic site (P) and one hydrophobic aromatic ring (R). Excellent statistical results of QSAR model such as good correlation coefficient (r > 0.9), higher F value (F > 20), excellent predictive power (Q2 > 0.6) and higher enrichment of known actives during virtual screening application strongly suggest that the developed model will be highly useful in designing new inhibitors and for predicting activity of new inhibitors.
Keywords: Anti-Alzheimers, Dyrk1A, Leucettines, Pharmacophore model, 3D-QSAR, Partial least square analysis.
Letters in Drug Design & Discovery
Title:Pharmacophore Based 3D-QSAR Modeling and Molecular Docking of Leucettines as Potent Dyrk1A Inhibitors
Volume: 10 Issue: 8
Author(s): Anu Bahl, Prashant Joshi, Sandip B. Bharate and Harish Chopra
Affiliation:
Keywords: Anti-Alzheimers, Dyrk1A, Leucettines, Pharmacophore model, 3D-QSAR, Partial least square analysis.
Abstract: The elevated level of dual-specificity tyrosine phosphorylation-regulated kinase 1A (Dyrk1A) is associated with the pathology of neurodegenerative diseases and has been implicated in some neurobiological alterations of Down syndrome, such as mental retardation. In the present article, a pharmacophore based 3D-QSAR model was developed for a series of leucettines possessing Dyrk1A inhibitory activity. The crucial molecular features observed in the developed pharmacophore model that account for binding affinity of ligands with the enzyme, include three H-bond acceptors (A), one positive ionic site (P) and one hydrophobic aromatic ring (R). Excellent statistical results of QSAR model such as good correlation coefficient (r > 0.9), higher F value (F > 20), excellent predictive power (Q2 > 0.6) and higher enrichment of known actives during virtual screening application strongly suggest that the developed model will be highly useful in designing new inhibitors and for predicting activity of new inhibitors.
Export Options
About this article
Cite this article as:
Bahl Anu, Joshi Prashant, Bharate B. Sandip and Chopra Harish, Pharmacophore Based 3D-QSAR Modeling and Molecular Docking of Leucettines as Potent Dyrk1A Inhibitors, Letters in Drug Design & Discovery 2013; 10 (8) . https://dx.doi.org/10.2174/15701808113100890024
DOI https://dx.doi.org/10.2174/15701808113100890024 |
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
-
Ischemic Tolerance Induced by Normobaric Hyperoxia and Evaluation of Group I and II Metabotropic Glutamate Receptors
Current Neurovascular Research Mediterranean Diet and Risk of Dementia
Current Alzheimer Research Judging Children as Children
Adolescent Psychiatry Survey of NMDA Receptor-related Biomarkers for Depression
Current Pharmaceutical Design Other Activities
Current Bioactive Compounds Editorial: Signaling Molecules as Biomarkers and Therapeutic Targets for Alzheimer's Disease: A New Perspective
Current Alzheimer Research Influence of Physical Immobilization of dsDNA on Carbon Based Matrices of Electrochemical Sensors
Current Pharmaceutical Analysis Small Molecules Targeting the NMDA Receptor Complex as Drugs for Neuropathic Pain
Mini-Reviews in Medicinal Chemistry The Role of Adenosine in Alzheimers Disease
Current Neuropharmacology The Potential Effect of Fluorinated Compounds in the Treatment of Alzheimer’s Disease
Current Pharmaceutical Design G Protein-Coupled Receptor Signaling Complexity in Neuronal Tissue:Implications for Novel Therapeutics
Current Alzheimer Research P2X Receptors and Inflammation
Current Medicinal Chemistry Neuroprotective Effects of Exercise Treatments After Injury: The Dual Role of Neurotrophic Factors
Current Neuropharmacology Isolated Anosmia as a Presentation of COVID-19: An Experience in a Referral Hospital
Infectious Disorders - Drug Targets Thriving, Managing, and Struggling: A Mixed Methods Study of Adolescent African Refugees’ Psychosocial Adjustment
Adolescent Psychiatry subject Index To Volume 2
Current Topics in Medicinal Chemistry The Forgotten Cells: Role of Astrocytes in Mood Disorders During the Aging
Current Neuropharmacology Pain Management in Hematological Patients with Major Organ Dysfunctions and Comorbid Illnesses
Cardiovascular & Hematological Agents in Medicinal Chemistry Editorial: Mobile Technology and Naturalistic Study Designs in Addiction Research
Current Drug Abuse Reviews The Neuropharmacology of Implicit Learning
Current Neuropharmacology