Abstract
Antiandrogens bicalutamide, flutamide and enzalutamide etc. have been used in clinical trials to treat prostate cancer by binding to and antagonizing androgen receptor (AR). Although initially effective, the drug resistance problem will emerge eventually, which results in a high medical need for novel AR antagonist exploitation. Here in this work, to facilitate the rational design of novel AR antagonists, we studied the structure-activity relationships of a series of 2-quinolinone derivatives and investigated the structural requirements for their antiandrogenic activities. Different modeling methods, including 2D MLR, 3D CoMFA and CoMSIA, were implemented to evolve QSAR models. All these models, thoroughly validated, demonstrated satisfactory results especially for the good predictive abilities. The contour maps from 3D CoMFA and CoMSIA models provide visualized explanation of key structural characteristics relevant to the antiandrogenic activities, which is summarized to a position-specific conclusion at the end. The obtained results from this research are practically useful for rational design and screening of promising chemicals with high antiandrogenic activities.
Keywords: Androgen receptor (AR), comparative molecular field analysis (CoMFA), prostate cancer (PCa), comparative molecular similarity indices analysis (CoMSIA), multiple linear regression (MLR).
Combinatorial Chemistry & High Throughput Screening
Title:A Combined Quantitative Structure-Activity Relationship Research of Quinolinone Derivatives as Androgen Receptor Antagonists
Volume: 18 Issue: 9
Author(s): Yuwei Wang, Fang Bai, Hong Cao, Jiazhong Li, Huanxiang Liu and Paola Gramatica
Affiliation:
Keywords: Androgen receptor (AR), comparative molecular field analysis (CoMFA), prostate cancer (PCa), comparative molecular similarity indices analysis (CoMSIA), multiple linear regression (MLR).
Abstract: Antiandrogens bicalutamide, flutamide and enzalutamide etc. have been used in clinical trials to treat prostate cancer by binding to and antagonizing androgen receptor (AR). Although initially effective, the drug resistance problem will emerge eventually, which results in a high medical need for novel AR antagonist exploitation. Here in this work, to facilitate the rational design of novel AR antagonists, we studied the structure-activity relationships of a series of 2-quinolinone derivatives and investigated the structural requirements for their antiandrogenic activities. Different modeling methods, including 2D MLR, 3D CoMFA and CoMSIA, were implemented to evolve QSAR models. All these models, thoroughly validated, demonstrated satisfactory results especially for the good predictive abilities. The contour maps from 3D CoMFA and CoMSIA models provide visualized explanation of key structural characteristics relevant to the antiandrogenic activities, which is summarized to a position-specific conclusion at the end. The obtained results from this research are practically useful for rational design and screening of promising chemicals with high antiandrogenic activities.
Export Options
About this article
Cite this article as:
Wang Yuwei, Bai Fang, Cao Hong, Li Jiazhong, Liu Huanxiang and Gramatica Paola, A Combined Quantitative Structure-Activity Relationship Research of Quinolinone Derivatives as Androgen Receptor Antagonists, Combinatorial Chemistry & High Throughput Screening 2015; 18 (9) . https://dx.doi.org/10.2174/1386207318666150831125750
DOI https://dx.doi.org/10.2174/1386207318666150831125750 |
Print ISSN 1386-2073 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5402 |
Call for Papers in Thematic Issues
Artificial Intelligence Methods for Biomedical, Biochemical and Bioinformatics Problems
Recently, a large number of technologies based on artificial intelligence have been developed and applied to solve a diverse range of problems in the areas of biomedical, biochemical and bioinformatics problems. By utilizing powerful computing resources and massive amounts of data, methods based on artificial intelligence can significantly improve the ...read more
Eco-friendly Agents for Biological Control of Pathogenic Diseases
The discovery of an alternative biological approach to disease management includes work on medicinal products derived from natural sources as a starting point for the development of eco-friendly agents for these diseases and the injuries they cause, as well as reducing human contact with hazardous chemicals and their residues. We ...read more
Emerging trends in diseases mechanisms, noble drug targets and therapeutic strategies: focus on immunological and inflammatory disorders
Recently infectious and inflammatory diseases have been a key concern worldwide due to tremendous morbidity and mortality world Wide. Recent, nCOVID-9 pandemic is a good example for the emerging infectious disease outbreak. The world is facing many emerging and re-emerging diseases out breaks at present however, there is huge lack ...read more
Exploring Spectral Graph Theory in Combinatorial Chemistry
Scope of the Thematic Issue: Combinatorial chemistry involves the synthesis and analysis of a large number of diverse compounds simultaneously. Traditional methods rely on brute force experimentation, which can be time-consuming and resource-intensive. Spectral Graph Theory, a branch of mathematics dealing with the properties of graphs in relation to 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
-
Flavonoids in Cancer Prevention
Anti-Cancer Agents in Medicinal Chemistry The Role of CD40 Expression in Dendritic Cells in Cancer Biology; A Systematic Review
Current Cancer Drug Targets The Role of Culture and Ethnicity in the Adjustment to Gynecological Cancer
Current Women`s Health Reviews An Update on Peptide Drugs for Voltage-Gated Calcium Channels
Recent Patents on CNS Drug Discovery (Discontinued) Current Advances and Therapeutic Potential of Agents Targeting Dipeptidyl Peptidases-IV, -II, 8/9 and Fibroblast Activation Protein
Current Topics in Medicinal Chemistry Pharmacological Perspectives of Wasp Venom
Protein & Peptide Letters Drug Resistance and Apoptosis in Cancer Treatment: Development of New Apoptosis-Inducing Agents Active in Drug Resistant Malignancies
Current Medicinal Chemistry - Anti-Cancer Agents Targeting the Tumor Stroma with Peroxisome Proliferator Activated Receptor (PPAR) Agonists
Anti-Cancer Agents in Medicinal Chemistry Aminobisphosphonates as New Weapons for γ δ T Cell-Based Immunotherapy of Cancer
Current Medicinal Chemistry Host Innate Immune Responses to Microbial Pathogens
Current Vascular Pharmacology Resveratrol: A New Potential Therapeutic Agent for Melanoma?
Current Medicinal Chemistry Monoclonal Antibodies as Cancer Therapeutics
Recent Patents on Biotechnology B7-H3-targeted Radioimmunotherapy of Human Cancer
Current Medicinal Chemistry Advancement Towards Tin-based Anticancer Chemotherapeutics: Structural Modification and Computer Modeling Approach to Drug-Enzyme Interactions
Current Topics in Medicinal Chemistry Cognitive Function and Quality of Life in Mild Thyroid Hormone Deficiency
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Current Advances in Therapy for Metastatic Melanoma
Current Cancer Therapy Reviews Phosphodiesterase 5 Inhibitors - Drug Design and Differentiation Based on Selectivity, Pharmacokinetic and Efficacy Profiles
Current Pharmaceutical Design Biomarkers of Asthma: Recent Patents from 2009-2011
Recent Patents on Biomarkers Transcription, DNA Damage and Beyond: The Roles of Histone Ubiquitination and Deubiquitination
Current Protein & Peptide Science Uncoupling Protein-2 and the Potential Link Between Metabolism and Longevity
Current Aging Science