Abstract
A topological-mathematical model obtained by linear discriminant analysis has been used to the search of new nonsteroidal antinflammatory drugs (NSAIDs). After carrying out an in silico screening based on such a model, on the Aldrich database, new structures potentially active were selected. Among these structures stand fourteen compounds, from which only one had been previously recorded as NSAID in the literature. The experimental tests performed on the remaining substances demonstrated that several compounds showed either in vitro or in vivo or both activity. Moreover, four compounds, namely 1,3-bis(benzyloxycarbonyl)-2-methyl-2-thiopseudourea, 4,6-dichloro-2-methylthio-5-phenylpyrimidine, 2-chloro-2,6-acetoxylidide and trans-1,3-diphenyl-2-propen-1-ol, showed a significant in vivo antinflammatory activity as compared to the reference drug (indomethacin). These results reinforce the role of Molecular Topology as a useful tool for drug discovery.
Keywords: COX-1 and COX-2 Inhibitors, Linear Discriminant Analisis, Molecular Topology, Nonsteroidal Antinflammatory
Letters in Drug Design & Discovery
Title: Application of Molecular Topology to the Search of Novel NSAIDs: Experimental Validation of Activity
Volume: 7 Issue: 6
Author(s): Maria Galvez-Llompart, Rosa M. Giner, Maria C. Recio, Sanzio Candeletti and Ramon Garcia-Domenech
Affiliation:
Keywords: COX-1 and COX-2 Inhibitors, Linear Discriminant Analisis, Molecular Topology, Nonsteroidal Antinflammatory
Abstract: A topological-mathematical model obtained by linear discriminant analysis has been used to the search of new nonsteroidal antinflammatory drugs (NSAIDs). After carrying out an in silico screening based on such a model, on the Aldrich database, new structures potentially active were selected. Among these structures stand fourteen compounds, from which only one had been previously recorded as NSAID in the literature. The experimental tests performed on the remaining substances demonstrated that several compounds showed either in vitro or in vivo or both activity. Moreover, four compounds, namely 1,3-bis(benzyloxycarbonyl)-2-methyl-2-thiopseudourea, 4,6-dichloro-2-methylthio-5-phenylpyrimidine, 2-chloro-2,6-acetoxylidide and trans-1,3-diphenyl-2-propen-1-ol, showed a significant in vivo antinflammatory activity as compared to the reference drug (indomethacin). These results reinforce the role of Molecular Topology as a useful tool for drug discovery.
Export Options
About this article
Cite this article as:
Galvez-Llompart Maria, M. Giner Rosa, C. Recio Maria, Candeletti Sanzio and Garcia-Domenech Ramon, Application of Molecular Topology to the Search of Novel NSAIDs: Experimental Validation of Activity, Letters in Drug Design & Discovery 2010; 7 (6) . https://dx.doi.org/10.2174/157018010791306597
DOI https://dx.doi.org/10.2174/157018010791306597 |
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
-
Discovery and Development of Natural Products and their Derivatives as Photosensitizers for Photodynamic Therapy
Current Medicinal Chemistry Plasma-Activated Solutions for Bacteria and Biofilm Inactivation
Current Bioactive Compounds Non-Cholinergic Pharmacotherapy Approaches to Alzheimers Disease: The Use of Non-Steroidal Anti-Inflammatory Drugs
CNS & Neurological Disorders - Drug Targets A New Light Device for Wound Healing
Recent Patents on Biomedical Engineering (Discontinued) Cigarette Smoke Exposure Inhibits Early Phase of Antibody Production through Inhibition of Immune Functions in Alveolar Macrophage
Current Respiratory Medicine Reviews Porphyromonas Gingivalis Antigenic Determinants - Potential Targets for the Vaccine Development against Periodontitis
Infectious Disorders - Drug Targets Polymers for Drug Eluting Stents
Current Pharmaceutical Design A Review of Five Automatic Point Correspondence Methods for Application on Medical Images
Current Medical Imaging Mechanisms Underlying the Cardiovascular Effects of COX-Inhibition: Benefits and Risks
Current Pharmaceutical Design Aloe-emodin: Progress in Pharmacological Activity, Safety, and Pharmaceutical Formulation Applications
Mini-Reviews in Medicinal Chemistry Dietary Intake and Bone Status with Aging
Current Pharmaceutical Design Anatomical and Functional Relationships Between Sensory Nerves and Mast Cells
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Teeth with Apical Periodontitis Obturated in the Presence or Absence of Cultivable Micro-Organisms: A Two-Year Prospective Study of Treatment Outcomes
Current Dentistry Cytokine Polymorphisms in Chronic Inflammatory Diseases with Reference to Occupational Diseases
Current Molecular Medicine Functional and Molecular Changes of MSCs in Aging
Current Stem Cell Research & Therapy New Potential Targets to Modulate Neutrophil Function in Inflammation
Mini-Reviews in Medicinal Chemistry Amalgamation of Stem Cells with Nanotechnology: A Unique Therapeutic Approach
Current Stem Cell Research & Therapy Drug in Adhesive Transdermal Formulation of Valsartan and Nifedipine: Pharmacokinetics and Pharmacodynamics in Rats
Current Drug Therapy Does It Make Sense that Diabetes is Reciprocally Associated with Periodontal Disease?
Endocrine, Metabolic & Immune Disorders - Drug Targets Optimal antibiotic dosage for chronic kidney disease patient: a pharmacological manual for oral clinicians
Recent Patents on Anti-Infective Drug Discovery