Abstract
Selective human butyrylcholinesterase (BChE) inhibitors such as cymserine have shown considerable promise for restoring cognition in Alzheimers disease. Recently, (-)-debromoflustramine B, 1, a hexahydropyrrolo-[2,3-b]indole natural product isolated from the marine bryozoan Flustra foliacea, has demonstrated micromolar potency as a selective BChE inhibitor. Since (±)-demethyldebromoflustramine B, (±)-2, has an even lower IC50, and the active enantiomer is (-)- 2, derivatives of (-)-2 were constructed in silico and docked into the active site of BChE. Several compounds exhibited improved inhibitor potency and could be candidates for future synthesis and in vitro enzyme inhibition study.
Keywords: Butyrylcholinesterase, Alzheimer's, inhibitor, debromoflustramine, demethyldebromoflustramine, docking, Flustra foliacea
Medicinal Chemistry
Title: In Silico Ligand-Receptor Docking of Potentially Selective Butyrylcholinesterase Inhibitors Structurally Related to the Marine Natural Product Debromoflustramine B
Volume: 6 Issue: 3
Author(s): Miguel O. Mitchell, Robert W. Figliozzi and Mustafa Guzel
Affiliation:
Keywords: Butyrylcholinesterase, Alzheimer's, inhibitor, debromoflustramine, demethyldebromoflustramine, docking, Flustra foliacea
Abstract: Selective human butyrylcholinesterase (BChE) inhibitors such as cymserine have shown considerable promise for restoring cognition in Alzheimers disease. Recently, (-)-debromoflustramine B, 1, a hexahydropyrrolo-[2,3-b]indole natural product isolated from the marine bryozoan Flustra foliacea, has demonstrated micromolar potency as a selective BChE inhibitor. Since (±)-demethyldebromoflustramine B, (±)-2, has an even lower IC50, and the active enantiomer is (-)- 2, derivatives of (-)-2 were constructed in silico and docked into the active site of BChE. Several compounds exhibited improved inhibitor potency and could be candidates for future synthesis and in vitro enzyme inhibition study.
Export Options
About this article
Cite this article as:
Mitchell O. Miguel, Figliozzi W. Robert and Guzel Mustafa, In Silico Ligand-Receptor Docking of Potentially Selective Butyrylcholinesterase Inhibitors Structurally Related to the Marine Natural Product Debromoflustramine B, Medicinal Chemistry 2010; 6 (3) . https://dx.doi.org/10.2174/1573406411006030141
DOI https://dx.doi.org/10.2174/1573406411006030141 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
- 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
-
<i>In-silico</i> Studies and Biological Activity of Potential BACE-1 Inhibitors
Combinatorial Chemistry & High Throughput Screening Is there a Rational Approach for Increasing Drug Specificity? Considerations on CNS Target Choice and Validation
Recent Patents on CNS Drug Discovery (Discontinued) The Effects of Lipid-Regulating Therapy on Haemostatic Parameters
Current Pharmaceutical Design Adverse Effects of Statins - Myths and Reality
Current Pharmaceutical Design Promising Therapies for Alzheimer's Disease
Current Pharmaceutical Design C-Reactive Protein: Interaction with the Vascular Endothelium and Possible Role in Human Atherosclerosis
Current Pharmaceutical Design Effectiveness of Nasal Continuous Positive Airway Pressure (CPAP) Therapy on Cardiovascular Outcomes in Obstructive Sleep Apnea-Hypopnea Syndrome (OSAHS)
Current Respiratory Medicine Reviews Telomere/Telomerase System: A New Target of Statins Pleiotropic Effect?
Current Vascular Pharmacology Selegiline (l-Deprenyl) as a Unique Neuroprotective Agent for Chronic Neurodegenerative Disorders- A Lesson from MAO Inhibition
Current Medicinal Chemistry - Central Nervous System Agents Crosstalk Between Covid-19 and Associated Neurological Disorders: A Review
Current Neuropharmacology Medical Treatment of Critical Limb Ischemia: Current State and Future Directions
Current Vascular Pharmacology Natural Product Formulations for the Prevention and Treatment of Alzheimer's disease: A Patent Review
Recent Patents on Drug Delivery & Formulation Adalimumab
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Low Dose of Anisodine Hydrobromide Induced Neuroprotective Effects in Chronic Cerebral Hypoperfusion Rats
CNS & Neurological Disorders - Drug Targets Synthesis and Cholinesterase Inhibition Activity of New Pyrrolopyrimidine Derivatives
Letters in Drug Design & Discovery ACAT1 as a Therapeutic Target and its Genetic Relationship with Alzheimer's Disease
Current Alzheimer Research Thromboembolic Complications in Malignant Haematological Disorders
Current Vascular Pharmacology The Role of Genes (and Environmental Stress) in Depression: An Update
Current Psychiatry Reviews The Hydroxamic Acids as Potential Anticancer and Neuroprotective Agents
Current Medicinal Chemistry New Insight into the Mechanisms of <i>Ginkgo Biloba</i> Extract in Vascular Aging Prevention
Current Vascular Pharmacology