Abstract
Glycogen synthase kinase-3β (GSK-3β) is a promising target for therapeutic invasion of Alzheimer’s disease (AD). The kinase enzyme plays major role in pathological process for the formation of β-amyloid plaques and neurofibrillary tangles in AD. In the present study, structure-based pharmacophore and ligand-based 3D QSAR, HQSAR and pharmacophore mapping studies have been emphasized to explore the possible structural requirement of this potential kinase inhibitors using a structurally diverse set of compounds. The developed models were validated with the interaction study at the catalytic cleft. The 3D QSAR studies yield robust models of CoMFA R2 = 0.965, se = 0.212, Q2 = 0.525, R2pred = 0.709, r2m = 0.579 and CoMSIA: R2 = 0.935, se = 0.289, Q2 = 0.581, R2pred = 0.723, r2m = 0.935, that explain the importance of steric, electrostatic, hydrogen bond (HB) acceptor of the molecule for inhibition of GSK-3β. The HQSAR study (R2 = 0.871, se = 0.400, Q2 = 0.639, R2pred = 0.721, r2m = 0.664) indicated the fragments of the molecular fingerprints that might be important for inhibition. Both structure- and ligand-based pharmacophore mapping proposed that acceptor and donor features of the molecule are essential for receptor–ligand interactions. Molecular diversity provides an opportunity on wide range of applicability for the GSK-3β inhibitors, and depicts information on the structural and properties requirement for effective binding at the active site selectivity that minimize the side effects with therapeutic benefits.
Keywords: GSK-3β, CoMFA, CoMSIA, HQSAR, pharmacophore mapping, e-pharmacophore.
Combinatorial Chemistry & High Throughput Screening
Title:Exploring Structural and Physicochemical Profiles of Potential GSK-3β Inhibitors Using Structure- and Ligand-Based Modeling Studies
Volume: 19 Issue: 4
Author(s): Tabassum Hossain, Achintya Saha and Arup Mukherjee
Affiliation:
Keywords: GSK-3β, CoMFA, CoMSIA, HQSAR, pharmacophore mapping, e-pharmacophore.
Abstract: Glycogen synthase kinase-3β (GSK-3β) is a promising target for therapeutic invasion of Alzheimer’s disease (AD). The kinase enzyme plays major role in pathological process for the formation of β-amyloid plaques and neurofibrillary tangles in AD. In the present study, structure-based pharmacophore and ligand-based 3D QSAR, HQSAR and pharmacophore mapping studies have been emphasized to explore the possible structural requirement of this potential kinase inhibitors using a structurally diverse set of compounds. The developed models were validated with the interaction study at the catalytic cleft. The 3D QSAR studies yield robust models of CoMFA R2 = 0.965, se = 0.212, Q2 = 0.525, R2pred = 0.709, r2m = 0.579 and CoMSIA: R2 = 0.935, se = 0.289, Q2 = 0.581, R2pred = 0.723, r2m = 0.935, that explain the importance of steric, electrostatic, hydrogen bond (HB) acceptor of the molecule for inhibition of GSK-3β. The HQSAR study (R2 = 0.871, se = 0.400, Q2 = 0.639, R2pred = 0.721, r2m = 0.664) indicated the fragments of the molecular fingerprints that might be important for inhibition. Both structure- and ligand-based pharmacophore mapping proposed that acceptor and donor features of the molecule are essential for receptor–ligand interactions. Molecular diversity provides an opportunity on wide range of applicability for the GSK-3β inhibitors, and depicts information on the structural and properties requirement for effective binding at the active site selectivity that minimize the side effects with therapeutic benefits.
Export Options
About this article
Cite this article as:
Hossain Tabassum, Saha Achintya and Mukherjee Arup, Exploring Structural and Physicochemical Profiles of Potential GSK-3β Inhibitors Using Structure- and Ligand-Based Modeling Studies, Combinatorial Chemistry & High Throughput Screening 2016; 19 (4) . https://dx.doi.org/10.2174/1386207319666160411125646
DOI https://dx.doi.org/10.2174/1386207319666160411125646 |
Print ISSN 1386-2073 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5402 |
Call for Papers in Thematic Issues
Artificial Intelligence Methods for Biomedical, Biochemical and Bioinformatics Problems
Recently, a large number of technologies based on artificial intelligence have been developed and applied to solve a diverse range of problems in the areas of biomedical, biochemical and bioinformatics problems. By utilizing powerful computing resources and massive amounts of data, methods based on artificial intelligence can significantly improve the ...read more
Eco-friendly Agents for Biological Control of Pathogenic Diseases
The discovery of an alternative biological approach to disease management includes work on medicinal products derived from natural sources as a starting point for the development of eco-friendly agents for these diseases and the injuries they cause, as well as reducing human contact with hazardous chemicals and their residues. We ...read more
Emerging trends in diseases mechanisms, noble drug targets and therapeutic strategies: focus on immunological and inflammatory disorders
Recently infectious and inflammatory diseases have been a key concern worldwide due to tremendous morbidity and mortality world Wide. Recent, nCOVID-9 pandemic is a good example for the emerging infectious disease outbreak. The world is facing many emerging and re-emerging diseases out breaks at present however, there is huge lack ...read more
Exploring Spectral Graph Theory in Combinatorial Chemistry
Scope of the Thematic Issue: Combinatorial chemistry involves the synthesis and analysis of a large number of diverse compounds simultaneously. Traditional methods rely on brute force experimentation, which can be time-consuming and resource-intensive. Spectral Graph Theory, a branch of mathematics dealing with the properties of graphs in relation to the ...read more
- 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
-
Applications of Umbilical Cord Derived Mesenchymal Stem Cells in Autoimmune and Immunological Disorders: From Literature to Clinical Practice
Current Stem Cell Research & Therapy Influence of Essential Trace Minerals and Micronutrient Insufficiencies on Harmful Metal Overload in a Mongolian Patient with Multiple Sclerosis
Current Aging Science Transmembrane Protein 166 and its Significance
Protein & Peptide Letters The Pro-Apoptotic Substance Thapsigargin Selectively Stimulates Re-Growth of Brain Capillaries
Current Neurovascular Research Recent Knowledge on Molecular Components of Lewy Bodies Discloses Future Therapeutic Strategies in Parkinsons Disease
Current Drug Targets - CNS & Neurological Disorders Caspase-3 Short Hairpin RNAs: A Potential Therapeutic Agent in Neurodegeneration of Aluminum-Exposed Animal Model
Current Alzheimer Research Cannabinoids and Neurodegenerative Diseases
CNS & Neurological Disorders - Drug Targets Current Overview of Inorganic Nanoparticles for the Treatment of Central Nervous System (CNS) Diseases
Current Nanomaterials The Peripheral Benzodiazepine Receptor: A Promising Therapeutic Drug Target
Current Medicinal Chemistry Clinical Uses of Melatonin in Neurological Diseases and Mental and Behavioural Disorders
Current Medicinal Chemistry Therapeutic Options in Prevention and Treatment of Aspartoacylase Gene Mutation Resulting Abnormalities in Canavan Disease
Current Pharmacogenomics Pituitary Adenylate Cyclase Activating Polypeptide in Animal Models of Neurodegenerative Disorders - Implications for Huntington and Parkinsons Diseases
Letters in Drug Design & Discovery Signaling Mechanisms Underlying Aβ Toxicity: Potential Therapeutic Targets for Alzheimers Disease
CNS & Neurological Disorders - Drug Targets Editorial [Hot Topic: Innate Immune Responses in CNS Neurodegenerative Diseases (Guest Editors: Hans van Noort and Sandra Amor)]
CNS & Neurological Disorders - Drug Targets Commentary-1 Research Highlights (Never Underestimate the Power of Adenosine in Multiple Sclerosis)
CNS & Neurological Disorders - Drug Targets Drosophila melanogaster in the Study of Human Neurodegeneration
CNS & Neurological Disorders - Drug Targets Targeting Epigenetics in Nervous System Disease
CNS & Neurological Disorders - Drug Targets PSEN1 Promoter Demethylation in Hyperhomocysteinemic TgCRND8 Mice is the Culprit, not the Consequence
Current Alzheimer Research Role of Reactive Oxygen Species in Estrogen Dependant Breast Cancer Complication
Anti-Cancer Agents in Medicinal Chemistry Melatonin, Autophagy and Intestinal Bowel Disease
Current Pharmaceutical Design