Abstract
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive dementia and loss of cognitive abilities. Until now, AD remains incurable. The principal biological target for AD therapy is acetylcholinesterase (AChE). Thus, the search for new drug candidates like AChE inhibitors constitutes an essential part for the discovery of more potent anti-AD agents. In general terms, rational drug design methodologies have played a decisive role. The present work is focused on the current state of the Ligand-Based Drug Design (LBDD) methods which have been applied to the elucidation of new molecular entities with high anti-AChE activity. Also, as a contribution to this field, we suggest a promising fragment-based approach for the search and prediction of new AChE inhibitors and for the fast and efficient extraction of substructural alerts which are responsible for the anti-AChE activity.
Keywords: AChE inhibitors, QSAR, 3D-QSAR, linear discriminant analysis, fragments, AChE, anti-AD agents, Ligand-Based Virtual Screening (LB-VS), parsimony, ArOCON, LBDD
Mini-Reviews in Medicinal Chemistry
Title:Discovery of Anti-Alzheimer Agents: Current Ligand-Based Approaches toward the Design of Acetylcholinesterase Inhibitors
Volume: 12 Issue: 6
Author(s): A. Speck-Planche, F. Luan and M. N.D.S. Cordeiro
Affiliation:
Keywords: AChE inhibitors, QSAR, 3D-QSAR, linear discriminant analysis, fragments, AChE, anti-AD agents, Ligand-Based Virtual Screening (LB-VS), parsimony, ArOCON, LBDD
Abstract: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive dementia and loss of cognitive abilities. Until now, AD remains incurable. The principal biological target for AD therapy is acetylcholinesterase (AChE). Thus, the search for new drug candidates like AChE inhibitors constitutes an essential part for the discovery of more potent anti-AD agents. In general terms, rational drug design methodologies have played a decisive role. The present work is focused on the current state of the Ligand-Based Drug Design (LBDD) methods which have been applied to the elucidation of new molecular entities with high anti-AChE activity. Also, as a contribution to this field, we suggest a promising fragment-based approach for the search and prediction of new AChE inhibitors and for the fast and efficient extraction of substructural alerts which are responsible for the anti-AChE activity.
Export Options
About this article
Cite this article as:
Speck-Planche A., Luan F. and N.D.S. Cordeiro M., Discovery of Anti-Alzheimer Agents: Current Ligand-Based Approaches toward the Design of Acetylcholinesterase Inhibitors, Mini-Reviews in Medicinal Chemistry 2012; 12 (6) . https://dx.doi.org/10.2174/138955712800493744
DOI https://dx.doi.org/10.2174/138955712800493744 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
Call for Papers in Thematic Issues
Bioprospecting of Natural Products as Sources of New Multitarget Therapies
According to the Convention on Biological Diversity, bioprospecting is the exploration of biodiversity and indigenous knowledge to develop commercially valuable products for pharmaceutical and other applications. Bioprospecting involves searching for useful organic compounds in plants, fungi, marine organisms, and microorganisms. Natural products traditionally constituted the primary source of more than ...read more
Computational Frontiers in Medicinal Chemistry
The thematic issue "Computational Frontiers in Medicinal Chemistry" provides a robust platform for delving into state-of-the-art computational methodologies and technologies that significantly propel advancements in medicinal chemistry. This edition seeks to amalgamate top-tier reviews spotlighting the latest trends and breakthroughs in the fusion of computational approaches, including artificial intelligence (AI) ...read more
Natural Products and Dietary Supplements in Alleviation of Metabolic, Cardiovascular, and Neurological Disorders
Metabolic disorders like diabetes, obesity, inflammation, oxidative stress, cancer etc, cardiovascular disorders like angina, myocardial infarction, congestive heart failure etc as well as neurological disorders like Alzheimer?s, Parkinson?s, Epilepsy, Depression, etc are the global burden. They covered the major segment of the diseases and disorders from which the human community ...read more
Natural Products in Drug Discovery
Natural products have always been one of the important ways of drug discovery due to their novel skeleton and diverse functional group characteristics. According to statistics, between 1981 and 2019, the FDA approved a total of 1,394 small molecule drugs for marketing, of which 930 marketed drugs originated from 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
-
Chest Pain, Panic Disorder and Coronary Artery Disease: A Systematic Review
CNS & Neurological Disorders - Drug Targets The Multifactorial Nature of Alzheimer's Disease for Developing Potential Therapeutics
Current Topics in Medicinal Chemistry Recent Advances in Treatment Approaches to Gaucher Disease
Current Pharmaceutical Biotechnology Modulation of Amyloid β Peptide1-42 Cytotoxicity and Aggregation in Vitro by Glucose and Chondroitin Sulfate
Current Alzheimer Research Alzheimer's Disease: Emerging Trends in Small Molecule Therapies
Current Medicinal Chemistry Progress in Understanding Basal Ganglia Dysfunction as a Common Target for Methamphetamine Abuse and HIV-1 Neurodegeneration
Current HIV Research APOE Genotypes and Brain Imaging Classes in Normal Cognition, Mild Cognitive Impairment, and Alzheimer’s Disease: A Longitudinal Study
Current Alzheimer Research COVID-19: The Significance of Platelets, Mitochondria, Vitamin D, Serotonin and the Gut Microbiota
Current Medicinal Chemistry LRRK2 Kinase Inhibition as a Therapeutic Strategy for Parkinson’s Disease, Where Do We Stand?
Current Neuropharmacology Trigonelline: A Plant Alkaloid with Therapeutic Potential for Diabetes and Central Nervous System Disease
Current Medicinal Chemistry Therapeutic Potential of N-Acetylcysteine for Wound Healing, Acute Bronchiolitis, and Congenital Heart Defects
Current Drug Metabolism Patent Selections
Recent Patents on CNS Drug Discovery (Discontinued) Cardiovascular Toxicity of Cyclooxygenase Inhibitors and Promising Natur a l Substitutes
Current Pharmaceutical Design Development of a Triggered Nocturnal Blood Pressure Monitoring which Detects Nighttime Blood Pressure Surges in Sleep Apnea Syndrome
Current Hypertension Reviews Neurogenesis in the Adult Brain: Implications for Alzheimers Disease
CNS & Neurological Disorders - Drug Targets Frontotemporal Lobar Degeneration (FTLD): Review and Update for Clinical Neurologists
Current Alzheimer Research The Pro-Apoptotic Substance Thapsigargin Selectively Stimulates Re-Growth of Brain Capillaries
Current Neurovascular Research Pathological Reorganization of NMDA Receptors Subunits and Postsynaptic Protein PSD-95 Distribution in Alzheimer’s Disease
Current Alzheimer Research Brain Perfusion In Sepsis
Current Vascular Pharmacology Transthyretin Deposition in Familial Amyloidotic Polyneuropathy
Current Medicinal Chemistry