Abstract
The interest for acetylcholinesterase as a target for the palliative treatment of Alzheimers disease has been renewed in the last years owing to the evidences that support the role of this enzyme in accelerating the aggregation and deposition of the β-amyloid peptide. A large amount of structural information on the acetylcholinesterase enzyme and of its complexes with inhibitors acting at the catalytic site, the peripheral binding site, or both is now available. Based on that, molecular modelling studies can be intensively used to decipher the molecular determinants that mediate the relationship between chemical structure and inhibitory potency. In turn, this knowledge can be exploited to design new compounds leading to more effective cholinergic strategies. At this point, inhibitors able to interact at the peripheral binding site are of particular relevance, as they might disrupt the interactions between the enzyme acetylcholinesterase and the β-amyloid peptide. Therefore, these compounds might not only ameliorate the cholinergic deficit, but also be capable of slowing down the progression of the disease.
Keywords: alzheimers disease, cholinesterase inhibitors, molecular modelling, structure-activity relationships
Current Pharmaceutical Design
Title: Molecular Modelling Approaches to the Design of Acetylcholinesterase Inhibitors: New Challenges for the Treatment of Alzheimers Disease
Volume: 10 Issue: 25
Author(s): J. Munoz-Muriedas, J. M. Lopez, Modesto Orozco and F. Javier Luque
Affiliation:
Keywords: alzheimers disease, cholinesterase inhibitors, molecular modelling, structure-activity relationships
Abstract: The interest for acetylcholinesterase as a target for the palliative treatment of Alzheimers disease has been renewed in the last years owing to the evidences that support the role of this enzyme in accelerating the aggregation and deposition of the β-amyloid peptide. A large amount of structural information on the acetylcholinesterase enzyme and of its complexes with inhibitors acting at the catalytic site, the peripheral binding site, or both is now available. Based on that, molecular modelling studies can be intensively used to decipher the molecular determinants that mediate the relationship between chemical structure and inhibitory potency. In turn, this knowledge can be exploited to design new compounds leading to more effective cholinergic strategies. At this point, inhibitors able to interact at the peripheral binding site are of particular relevance, as they might disrupt the interactions between the enzyme acetylcholinesterase and the β-amyloid peptide. Therefore, these compounds might not only ameliorate the cholinergic deficit, but also be capable of slowing down the progression of the disease.
Export Options
About this article
Cite this article as:
Munoz-Muriedas J., Lopez M. J., Orozco Modesto and Luque Javier F., Molecular Modelling Approaches to the Design of Acetylcholinesterase Inhibitors: New Challenges for the Treatment of Alzheimers Disease, Current Pharmaceutical Design 2004; 10 (25) . https://dx.doi.org/10.2174/1381612043383386
DOI https://dx.doi.org/10.2174/1381612043383386 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
- Announcements
Related Articles
-
Design of Iodine-Lithium-α-Dextrin Liquid Crystal with Potent Antimicrobial and Anti-Inflammatory Properties
Current Pharmaceutical Design Levetiracetam might act as an efficacious drug to attenuate cognitive deficits of Alzheimer’s disease
Current Topics in Medicinal Chemistry Tau Truncation is a Productive Posttranslational Modification of Neurofibrillary Degeneration in Alzheimer’s Disease
Current Alzheimer Research Proteases Essential for Human Influenza Virus Entry into Cells and Their Inhibitors as Potential Therapeutic Agents
Current Pharmaceutical Design Colostral Proline-Rich Polypeptides - Immunoregulatory Properties and Prospects of Therapeutic Use in Alzheimers Disease
Current Alzheimer Research Neuroactive Molecules in the Brains of Nonhuman Primates and Their Therapeutic Application to Neurodegenerative Disorders
Central Nervous System Agents in Medicinal Chemistry The Prevalence of Frailty in Patients Admitted to Hospital with Vertebral Fragility Fractures
Current Rheumatology Reviews Is the Use of Proton-pump Inhibitors a Risk Factor for Alzheimer’s Disease? Molecular Mechanisms and Clinical Implications
Current Medicinal Chemistry Fish Oil has Beneficial Effects on Behavior Impairment and Oxidative Stress in Rats Subjected to a Hepatic Encephalopathy Model
CNS & Neurological Disorders - Drug Targets Recent Progress in Cerebrovascular Gene Therapy
Current Neurovascular Research Editorial (Hot Topic: Therapeutic Targets in Neurodegenerative Diseases)
Current Enzyme Inhibition Therapeutic Targets in the Ubiquitin-proteasome System for Alzheimer's Disease
Current Enzyme Inhibition Glutamate Receptors in Human Caudate Nucleus in Normal Aging and Alzheimer’s Disease
Current Alzheimer Research Molecular Hybridization as a Tool for Designing Multitarget Drug Candidates for Complex Diseases
Current Topics in Medicinal Chemistry Enteric Ecosystem Disruption in Autism Spectrum Disorder: Can the Microbiota and Macrobiota be Restored?
Current Pharmaceutical Design Proteolytic Degradation of the Amyloid β-Protein: The Forgotten Side of Alzheimers Disease
Current Alzheimer Research Heparin Induced Thrombocytopenia: Pathogenetic, Clinical, Diagnostic and Therapeutic Aspects
Cardiovascular & Hematological Disorders-Drug Targets The APOE Genotype: Modification of Therapeutic Responses in Alzheimer's Disease
Current Pharmaceutical Design Methylenetetrahydrofolate Reductase: Biochemical Characterization and Medical Significance
Current Pharmaceutical Design Epigenetic Drugs for Multiple Sclerosis
Current Neuropharmacology