Abstract
Various derivatives of a modified estradiol core bearing a fused γ-lactone were designed as non-estrogenic inhibitors of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1). The compounds were synthesized, characterized and tested for their ability to inhibit enzyme activity (transformation of estrone into estradiol). The proliferative (estrogenic) activity of the compounds was also investigated on estrogen-sensitive breast cancer T-47D cells. Interestingly, one of the estradiol derivatives (compound 24) showed a dual action by inhibiting 17β-HSD1 (IC50 = 1.0 µM) and by producing an antiestrogenic effect on T-47D cells.
Keywords: Chemical synthesis, enzyme inhibitor, estrogen, lactone, steroid, 17β-hydroxysteroid dehydrogenase.
Current Enzyme Inhibition
Title:Synthesis and Biological Evaluation of Estradiol-Core Derivatives Bearing a Fused γ-Lactone as Inhibitors of 17β-Hydroxysteroid Dehydrogenase Type 1
Volume: 10 Issue: 1
Author(s): Etienne Ouellet, Diana Ayan and Donald Poirier
Affiliation:
Keywords: Chemical synthesis, enzyme inhibitor, estrogen, lactone, steroid, 17β-hydroxysteroid dehydrogenase.
Abstract: Various derivatives of a modified estradiol core bearing a fused γ-lactone were designed as non-estrogenic inhibitors of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1). The compounds were synthesized, characterized and tested for their ability to inhibit enzyme activity (transformation of estrone into estradiol). The proliferative (estrogenic) activity of the compounds was also investigated on estrogen-sensitive breast cancer T-47D cells. Interestingly, one of the estradiol derivatives (compound 24) showed a dual action by inhibiting 17β-HSD1 (IC50 = 1.0 µM) and by producing an antiestrogenic effect on T-47D cells.
Export Options
About this article
Cite this article as:
Ouellet Etienne, Ayan Diana and Poirier Donald, Synthesis and Biological Evaluation of Estradiol-Core Derivatives Bearing a Fused γ-Lactone as Inhibitors of 17β-Hydroxysteroid Dehydrogenase Type 1, Current Enzyme Inhibition 2014; 10 (1) . https://dx.doi.org/10.2174/1573408010666140118002739
DOI https://dx.doi.org/10.2174/1573408010666140118002739 |
Print ISSN 1573-4080 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6662 |
- 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
-
Molecularly Targeted Therapy in Breast Cancer: The New Generation
Recent Patents on Anti-Cancer Drug Discovery Patent Selections
Recent Patents on Drug Delivery & Formulation Molecular Mechanisms of Inflammation. Anti-Inflammatory Benefits of Virgin Olive Oil and the Phenolic Compound Oleocanthal
Current Pharmaceutical Design High Cytotoxicity and Apoptotic Effects of Natural Bioactive Benzofuran Derivative on the MCF-7 Breast Cancer Cell Line
Combinatorial Chemistry & High Throughput Screening Targeting IAPs as An Approach to Anti-Cancer Therapy
Current Topics in Medicinal Chemistry Current Strategies for the Treatment of Ulcerative Colitis
Recent Patents on Inflammation & Allergy Drug Discovery Vitamin E–TPGS Stabilized Self-Assembled Tripeptide Nanostructures for Drug Delivery
Current Topics in Medicinal Chemistry Integrative Approaches for microRNA Target Prediction: Combining Sequence Information and the Paired mRNA and miRNA Expression Profiles
Current Bioinformatics Delivery Systems for Applications in siRNA Technology
Drug Delivery Letters Biomarkers and Multiple Drug Resistance in Breast Cancer
Current Cancer Drug Targets Curcumin: A Potential Neuroprotective Agent in Parkinson's Disease
Current Pharmaceutical Design 10 Years of SELDI: What Have we Learnt?
Current Proteomics Targeting the Tumor Proteasome as a Mechanism to Control the Synthesis and Bioactivity of Matrix Macromolecules
Current Molecular Medicine Tankyrase as a Novel Molecular Target in Cancer and Fibrotic Diseases
Current Drug Targets Cross-Talk between Tumor Cells and the Microenvironment at the Metastatic Niche
Current Pharmaceutical Biotechnology The Rationale of Targeting Neutrophils with Dapsone during Glioblastoma Treatment
Anti-Cancer Agents in Medicinal Chemistry Disulfide Linkage: A Potent Strategy in Tumor-Targeting Drug Discovery
Current Medicinal Chemistry Combining Oncolytic Virotherapy and Cytotoxic Therapies to Fight Cancer
Current Pharmaceutical Design Anti-Invasive and Anti-Metastasis Strategies: New Roads, New Tools and New Hopes
Current Cancer Drug Targets Dihydropyrimidinones Scaffold as a Promising Nucleus for Synthetic Profile and Various Therapeutic Targets: A Review
Current Organic Synthesis