Abstract
Alzheimers disease has become one of the most serious healthcare problems nowadays, where age is clearly the major risk factor. The pathology of the disease is characterized by the formation of senile plaques outside the neurons, which are composed, predominantly, by the β-amyloid (Aβ) peptide. Considering that β-secretase is an aspartyl protease involved in the cleavage of the amyloid precursor, the first step required for the formation of Aβ, becomes an attractive therapeutic target for drug design. A virtual screening approach based on flexible docking was applied in order to identify potential inhibitor candidates of β-secretase, since the docking method used here showed to be able to reproduce the binding modes of crystallographic complexes. After validation, ten potential inhibitors were selected and evaluated with respect to the analysis of toxicological groups. The most promising inhibitor candidate was analyzed in a molecular dynamics trajectory to reinforce, theoretically, the potential inhibitory activity. Overall results obtained here suggest that this novel potential β-secretase inhibitor could be a promising pharmaceutical for the Alzheimers disease treatment.
Current Bioactive Compounds
Title: In Silico Search and Toxicology Prediction of Novel Potential β-Secretase Inhibitors in Alzheimers Disease
Volume: 5 Issue: 2
Author(s): Vinicius Barreto da Silva, Adriana Mieco Namba, Daniela Godoy Pantalena, Taina Ferreira do Prado and Carlos Henrique Tomich de Paula da Silva
Affiliation:
Abstract: Alzheimers disease has become one of the most serious healthcare problems nowadays, where age is clearly the major risk factor. The pathology of the disease is characterized by the formation of senile plaques outside the neurons, which are composed, predominantly, by the β-amyloid (Aβ) peptide. Considering that β-secretase is an aspartyl protease involved in the cleavage of the amyloid precursor, the first step required for the formation of Aβ, becomes an attractive therapeutic target for drug design. A virtual screening approach based on flexible docking was applied in order to identify potential inhibitor candidates of β-secretase, since the docking method used here showed to be able to reproduce the binding modes of crystallographic complexes. After validation, ten potential inhibitors were selected and evaluated with respect to the analysis of toxicological groups. The most promising inhibitor candidate was analyzed in a molecular dynamics trajectory to reinforce, theoretically, the potential inhibitory activity. Overall results obtained here suggest that this novel potential β-secretase inhibitor could be a promising pharmaceutical for the Alzheimers disease treatment.
Export Options
About this article
Cite this article as:
da Silva Barreto Vinicius, Namba Mieco Adriana, Pantalena Godoy Daniela, do Prado Ferreira Taina and de Paula da Silva Tomich Carlos Henrique, In Silico Search and Toxicology Prediction of Novel Potential β-Secretase Inhibitors in Alzheimers Disease, Current Bioactive Compounds 2009; 5 (2) . https://dx.doi.org/10.2174/157340709788452000
DOI https://dx.doi.org/10.2174/157340709788452000 |
Print ISSN 1573-4072 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6646 |
- 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
-
Alzheimers Disease and n-3 Polyunsaturated Fatty Acids: Beneficial Effects and Possible Molecular Pathways Involved
Current Signal Transduction Therapy Bilateral Interrelationship of Diabetes and Periodontium
Current Diabetes Reviews Small Artery Remodeling in Obesity and Insulin Resistance
Current Vascular Pharmacology Herb-Drug Interactions in Neurological Disorders: A Critical Appraisal
Current Drug Metabolism Dipeptidyl Peptidase-4 Inhibition: Linking Chemical Properties to Clinical Safety
Current Medicinal Chemistry Alzheimers Disease: Pathological Mechanisms and Recent Insights
Current Neuropharmacology Biochemical Properties of Indoleamine 2,3-dioxygenase: From Structure to Optimized Design of Inhibitors
Current Medicinal Chemistry Lipid-Based Nanocarriers for CNS-Targeted Drug Delivery
Recent Patents on CNS Drug Discovery (Discontinued) The Contribution of Cerebral Vascular Neuropathology to Mild Stage of Alzheimer’s Dementia Using the NACC Database
Current Alzheimer Research Ginkgo biloba Extract in Vascular Protection: Molecular Mechanisms and Clinical Applications
Current Vascular Pharmacology Pomegranate Extract Modulates Processing of Amyloid-β Precursor Protein in an Aged Alzheimer`s Disease Animal Model
Current Alzheimer Research Human Platelets Express Authentic CB1 and CB2 Receptors
Current Neurovascular Research Invokana (Canagliflozin) as a Dual Inhibitor of Acetylcholinesterase and Sodium Glucose Co-Transporter 2: Advancement in Alzheimer’s Disease- Diabetes Type 2 Linkage via an Enzoinformatics Study
CNS & Neurological Disorders - Drug Targets Adenosine A2A Receptor Antagonists and Parkinsons Disease: State of the Art and Future Directions
Current Pharmaceutical Design Sleep-Wake Patterns and Cognition of Older Adults with Amnestic Mild Cognitive Impairment (aMCI): A Comparison with Cognitively Healthy Adults and Moderate Alzheimer’s Disease Patients
Current Alzheimer Research Therapeutic Approaches Targeting Pathological Tau Aggregates
Current Pharmaceutical Design (±)-3,5-Bis(substitutedmethyl)pyrrolidines: Application to the Synthesis of Analogues of glycine-L-proline-L-glutamic Acid (GPE)
Current Organic Synthesis Silybin and Silymarin - New and Emerging Applications in Medicine
Current Medicinal Chemistry The Multifunctional Anti-inflammatory Drugs Used in the Therapy of Alzheimer’s Disease
Current Medicinal Chemistry The Potential Role of Glycogen Synthase Kinase 3 Inhibitors as Amyotrophic Lateral Sclerosis Pharmacological Therapy
Current Medicinal Chemistry