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
-
Approaches to Improve Efficiency of Dendritic Cell-based Therapy of High Grade Gliomas
Current Pharmaceutical Design Microenvironmental Regulation of Cancer Stem Cell Phenotypes
Current Stem Cell Research & Therapy Antitumor Properties of Natural Compounds and Related Molecules
Recent Patents on Anti-Cancer Drug Discovery Histone Lysine-Specific Methyltransferases and Demethylases in Carcinogenesis: New Targets for Cancer Therapy and Prevention
Current Cancer Drug Targets Transcriptionally Targeted Adenovirus Vectors
Current Gene Therapy Effective Anticancer Drug and Food Choices Based on Polyamine Levels in Cancer Tissues
Current Drug Therapy Rationale Design, Synthesis, Cytotoxicity Evaluation, and Molecular Docking Studies of 1,3,4-oxadiazole Analogues
Anti-Cancer Agents in Medicinal Chemistry Potential Deployment of Angiotensin I Converting Enzyme Inhibitors and of Angiotensin II Type 1 and Type 2 Receptor Blockers in Cancer Chemotherapy
Anti-Cancer Agents in Medicinal Chemistry Neuregulin Signaling in Pieces-Evolution of the Gene Family
Current Pharmaceutical Design Nasal Polyposis: An Overview of Differential Diagnosis and Treatment
Recent Patents on Inflammation & Allergy Drug Discovery Tumor Suppression by DNA Base Excision Repair
Mini-Reviews in Medicinal Chemistry Adrenoceptors: Non Conventional Target for Breast Cancer?
Current Medicinal Chemistry From Alpha to Omega with Aβ: Targeting the Multiple Molecular Appearances of the Pathogenic Peptide in Alzheimers Disease
Current Medicinal Chemistry DNA Drug Design for Cancer Therapy
Current Pharmaceutical Design Radiation and Gene Therapy: Rays of Hope for the New Millennium?
Current Gene Therapy Soy Phytoestrogens and Breast Cancer Chemoprevention: Molecular Mechanisms
Current Nutrition & Food Science Algal Biorefinery for the Extraction of Bioactive Compounds
Current Bioactive Compounds Apoptosis Induction by Erucylphosphohomocholine via the 18 kDa Mitochondrial Translocator Protein: Implications for Cancer Treatment
Anti-Cancer Agents in Medicinal Chemistry 4-Hydroxynonenal in the Pathogenesis and Progression of Human Diseases
Current Medicinal Chemistry Smart Polymer Based Delivery Systems for Peptides and Proteins
Recent Patents on Drug Delivery & Formulation