Abstract
The cytochrome-P450 (CYP) complex aromatase is the rate-limiting step in the production of endogenous estrogen. This synthesis can be controlled with aromatase inhibitor (AI). Different types of AIs are under extensive study for use in the treatment of advanced breast cancer in postmenopausal patients. In view of such significance, the present study explored the pharmacophores of benzofuran derivatives containing pyridine, imidazole and triazole substituents for inhibiting selective aromatase enzyme, CYP19 activity. Implementing classical QSAR (R2=0.858, Q2=0.737, s=0.349, R2 test=0.839) and space modeling (R2=0.908, Δ cost=179.138, rmsd=1.235, R2 test=0.867) approaches, it has been explored that molecular hydrophobicity, presence of suitable ring substituent and hydrogen bond acceptors are the crucial key features of the benzofuran scaffold for imparting CYP19 inhibitory activity. Moreover steric properties of the molecule have influence on the activity.
Keywords: Pharmacophore mapping, QSAR, Space modeling, Benzofuran derivatives, CYP19 aromatase inhibition
Letters in Drug Design & Discovery
Title: Pharmacophore Searching of Benzofuran Derivatives for Selective CYP19 Aromatase Inhibition
Volume: 6 Issue: 1
Author(s): Shuchi Nagar, Md Ataul Islam, Suvadra Das, Arup Mukherjee and Achintya Saha
Affiliation:
Keywords: Pharmacophore mapping, QSAR, Space modeling, Benzofuran derivatives, CYP19 aromatase inhibition
Abstract: The cytochrome-P450 (CYP) complex aromatase is the rate-limiting step in the production of endogenous estrogen. This synthesis can be controlled with aromatase inhibitor (AI). Different types of AIs are under extensive study for use in the treatment of advanced breast cancer in postmenopausal patients. In view of such significance, the present study explored the pharmacophores of benzofuran derivatives containing pyridine, imidazole and triazole substituents for inhibiting selective aromatase enzyme, CYP19 activity. Implementing classical QSAR (R2=0.858, Q2=0.737, s=0.349, R2 test=0.839) and space modeling (R2=0.908, Δ cost=179.138, rmsd=1.235, R2 test=0.867) approaches, it has been explored that molecular hydrophobicity, presence of suitable ring substituent and hydrogen bond acceptors are the crucial key features of the benzofuran scaffold for imparting CYP19 inhibitory activity. Moreover steric properties of the molecule have influence on the activity.
Export Options
About this article
Cite this article as:
Nagar Shuchi, Islam Ataul Md, Das Suvadra, Mukherjee Arup and Saha Achintya, Pharmacophore Searching of Benzofuran Derivatives for Selective CYP19 Aromatase Inhibition, Letters in Drug Design & Discovery 2009; 6 (1) . https://dx.doi.org/10.2174/157018009787158607
DOI https://dx.doi.org/10.2174/157018009787158607 |
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
-
Targeting Bcl-2 in CLL
Current Medicinal Chemistry The Role of the Complex USP1/WDR48 in Differentiation and Proliferation Processes in Cancer Stem Cells
Current Stem Cell Research & Therapy Dendritic Cells in Colorectal Cancer and a Potential for their Use in Therapeutic Approaches
Current Pharmaceutical Design Gene Expression Meta-Analysis of Potential Metastatic Breast Cancer Markers
Current Molecular Medicine Cancer and Cyclooxygenase-2 (COX-2) Inhibition
Current Pharmaceutical Design Oxidative Stress and Cellular Senescence: The Key Tumor-promoting Factors in Colon Cancer and Beneficial Effects of Polyphenols in Colon Cancer Prevention
Current Cancer Therapy Reviews Production, Purification and Characterization of Adeno-Associated Vectors
Current Gene Therapy Regulatory T Cells and Cancer Therapy: An Old Story with a New Hope
Current Cancer Therapy Reviews Natural Products Containing Olefinic Bond: Important Substrates for Semi-synthetic Modification Towards Value Addition
Current Organic Chemistry The Use of the Zebrafish Model to Aid in Drug Discovery and Target Validation
Current Topics in Medicinal Chemistry Patent Selections
Recent Patents on Anti-Cancer Drug Discovery Protective Effects of Melatonin and Mitochondria-targeted Antioxidants Against Oxidative Stress: A Review
Current Medicinal Chemistry Volatilome Metabolomics and Databases, Recent Advances and Needs
Current Metabolomics Coumarins as Promising Scaffold for the Treatment of Age-related Diseases – An Overview of the Last Five Years
Current Topics in Medicinal Chemistry Advances in Fish Cytokine Biology Give Clues to the Evolution of a Complex Network
Current Pharmaceutical Design Understanding Prostate Cancer Cells Metabolome: A Spectroscopic Approach
Current Metabolomics Antibody Recognition of Fluorinated Haptens and Antigens
Current Topics in Medicinal Chemistry Gene Polymorphisms and Pharmacogenetics in Rheumatoid Arthritis
Current Genomics Small Molecules as SIRT Modulators
Mini-Reviews in Medicinal Chemistry Autophagic Vacuole Secretion Triggered by Chidamide Participates in TRAIL Apoptosis Effect in Breast Cancer Cells
Current Pharmaceutical Design