Abstract
Alzheimers disease (AD) is a major neurodegenerative disease that affects mainly people over 65 years of age. The main therapeutic approach to AD is based on the use of acetylcholinesterase (AChE) inhibitors. Recent studies have shown that butyrylcholinesterase (BuChE) can also be considered an attractive target for the development of novel drugs for AD therapy. The design of new potent and selective BuChE inhibitors is of great importance in drug discovery. 2D quantitative structure-activity relationship studies were conducted on a series of potent inhibitors of human BuChE using classical and hologram QSAR (HQSAR) approaches. A training set of 40 compounds was employed to derive the models. Classical QSAR models showed moderate correlation (r2 = 0.836, q2 = 0.750), with no substantial predictive power for untested compounds. On the other hand, the best HQSAR model (r2 = 0.928, q2 = 0.723) was used to predict the potency of 10 test set compounds, and the predicted values were in good agreement with the experimental results, showing the potential of this model for new untested compounds.
Keywords: 2D QSAR, HQSAR, Alzheimer, Tacrine derivatives, Butyrylcholinesterase, Inhibitors
Letters in Drug Design & Discovery
Title: Classical and Hologram QSAR Studies on a Series of Tacrine Derivatives as Butyrylcholinesterase Inhibitors
Volume: 4 Issue: 2
Author(s): M. S. Castilho, R. V. C. Guido and A. D. Andricopulo
Affiliation:
Keywords: 2D QSAR, HQSAR, Alzheimer, Tacrine derivatives, Butyrylcholinesterase, Inhibitors
Abstract: Alzheimers disease (AD) is a major neurodegenerative disease that affects mainly people over 65 years of age. The main therapeutic approach to AD is based on the use of acetylcholinesterase (AChE) inhibitors. Recent studies have shown that butyrylcholinesterase (BuChE) can also be considered an attractive target for the development of novel drugs for AD therapy. The design of new potent and selective BuChE inhibitors is of great importance in drug discovery. 2D quantitative structure-activity relationship studies were conducted on a series of potent inhibitors of human BuChE using classical and hologram QSAR (HQSAR) approaches. A training set of 40 compounds was employed to derive the models. Classical QSAR models showed moderate correlation (r2 = 0.836, q2 = 0.750), with no substantial predictive power for untested compounds. On the other hand, the best HQSAR model (r2 = 0.928, q2 = 0.723) was used to predict the potency of 10 test set compounds, and the predicted values were in good agreement with the experimental results, showing the potential of this model for new untested compounds.
Export Options
About this article
Cite this article as:
Castilho S. M., C. Guido V. R. and Andricopulo D. A., Classical and Hologram QSAR Studies on a Series of Tacrine Derivatives as Butyrylcholinesterase Inhibitors, Letters in Drug Design & Discovery 2007; 4 (2) . https://dx.doi.org/10.2174/157018007779422505
DOI https://dx.doi.org/10.2174/157018007779422505 |
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
-
Dexrazoxane for the Prevention of Cardiac Toxicity and Treatment of Extravasation Injury from the Anthracycline Antibiotics
Current Pharmaceutical Biotechnology Drug Design Should Involve Consideration of Environmental Risk and Hazard
Letters in Drug Design & Discovery The Sigma Receptor: Evolution of the Concept in Neuropsychopharmacology
Current Neuropharmacology Ethanol Withdrawal and Hyperalgesia
Current Drug Abuse Reviews Dopamine Neurons in the Ventral Tegmental Area: Drug-induced Synaptic Plasticity and Its Role in Relapse to Drug-seeking Behavior
Current Drug Abuse Reviews Effects of Antiretroviral Therapy on Immunity in Patients Infected with HIV
Current Pharmaceutical Design The Effect of Vitamin D3 Supplementation on Serum BDNF, Dopamine, and Serotonin in Children with Attention-Deficit/Hyperactivity Disorder
CNS & Neurological Disorders - Drug Targets Soy Isoflavone Alleviates Aβ1-42-Induced Impairment of Learning and Memory Ability Through the Regulation of RAGE/LRP-1 in Neuronal and Vascular Tissue
Current Neurovascular Research Pharmacogenetics of the Human MDR1 Multidrug Transporter
Current Pharmacogenomics Selectivity Problems with Drugs Acting on Cardiac Na<sup>+</sup> and Ca<sup>2+</sup> Channels
Current Medicinal Chemistry The NK-1 Receptor is Involved in the Antitumoural Action of L-733,060 and in the Mitogenic Action of Substance P on Human Pancreatic Cancer Cell Lines
Letters in Drug Design & Discovery [11C]Meta-Hydroxyephedrine PET/CT
Current Radiopharmaceuticals Immunocal® and Preservation of Glutathione as a Novel Neuroprotective Strategy for Degenerative Disorders of the Nervous System
Recent Patents on CNS Drug Discovery (Discontinued) Cognitive Identity in Schizophrenia: Vision, Space, and Body Perception from Prodrome to Syndrome
Current Psychiatry Reviews Triazino-caffeine Derivatives by Intramolecular Cyclization: Synthesis, Characterization and Antimicrobial Studies
Letters in Organic Chemistry Steroid Receptor Ligands for Breast Cancer Targeting: An Insight into Their Potential Role As Pet Imaging Agents
Current Medicinal Chemistry Storage, Expression and Function of Fas Ligand, the Key Death Factor of Immune Cells
Current Medicinal Chemistry Properties and Potency of Small Molecule Agents for Treatment of Mycobacterium Tuberculosis Infections of the Central Nervous System
Central Nervous System Agents in Medicinal Chemistry 2-Arylindoles: A Privileged Molecular Scaffold with Potent, Broad-Ranging Pharmacological Activity
Current Medicinal Chemistry Application of Molecular Imaging Technologies in Antitumor Drug Development and Therapy
Current Pharmaceutical Design