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
-
Therapeutic Potential of Genus <i>Pongamia</i> and <i>Derris</i>: Phytochemical and Bioactivity
Mini-Reviews in Medicinal Chemistry Immune-Regulatory Mechanisms of Classical and Experimental Multiple Sclerosis Drugs: A Special Focus on Helminth-Derived Treatments
Current Medicinal Chemistry Imaging the Earliest Stages of Alzheimers Disease
Current Alzheimer Research The Role of CD8+ T Cells in Multiple Sclerosis and its Animal Models
Current Drug Targets - Inflammation & Allergy Does Diet Affect the Symptoms of ADHD?
Current Pharmaceutical Biotechnology New Potential Targets to Modulate Neutrophil Function in Inflammation
Mini-Reviews in Medicinal Chemistry Identification of Structural and Electronic Features for a Series of MCH1R Antagonists
Medicinal Chemistry Identification of Potential Dual Negative Allosteric Modulators of Group I mGluR Family: A Shape Based Screening, ADME Prediction, Induced Fit Docking and Molecular Dynamics Approach Against Neurodegenerative Diseases
Current Topics in Medicinal Chemistry Eating Disorder Symptoms and CYP2D6 Variation in Cuban Healthy Females: A Report from the Ibero-American Network of Pharmacogenetics
Current Pharmacogenomics and Personalized Medicine Unravelling the Role of Infectious Agents in the Pathogenesis of Human Autoimmunity: The Hypothesis of the Retroviral Involvement Revisited
Current Molecular Medicine PM6, PM7 and RM1 Quantum Chemistry Modeling of MEH-PPV and PEDOT Polymers
Current Physical Chemistry The Nanostructure of the Oriental Hornet (Hymenoptera, Vespinae) Cuticle and Silk and Some of their Biophysical Properties
Current Nanoscience Intracellular Expression of Inflammatory Proteins S100A8 and S100A9 Leads to Epithelial-mesenchymal Transition and Attenuated Aggressivity of Breast Cancer Cells
Anti-Cancer Agents in Medicinal Chemistry Alzheimer's Disease and Natural Products: Future Regimens Emerging from Nature
Current Topics in Medicinal Chemistry Cellular Niches for Endogenous Neural Stem Cells in the Adult Brain
CNS & Neurological Disorders - Drug Targets Vitamin D as a Potential Agent for Ischemic Axonal Regeneration after Epineurial Devascularization of the Sciatic Nerve
Current Neurovascular Research Correlates of Physical Activity of Children and Adolescents with Visual Impairments: A Systematic Review
Current Pharmaceutical Design Inhibition of Store-Operated Calcium Entry in Alzheimer’s Disease and the Associated Mechanisms
Current Alzheimer Research Fluoxetine Improves Behavioral Performance by Suppressing the Production of Soluble β-Amyloid in APP/PS1 Mice
Current Alzheimer Research The Glucocorticoid Receptor: Molecular Mechanism and New Therapeutic Opportunities
Current Drug Targets - Inflammation & Allergy