Abstract
In the overall scheme of the future development of new drugs for the treatment of breast cancer, specially tamoxifen resistant tumours, we have explored the unprecedented use of organometallic SERMs. The initial idea is to enhance the efficacy of the current standard, i.e. tamoxifen, by modifying the structure through judicious incorporation of an organometallic moiety possessing novel properties. Results have been varied, justifying a systematic approach that has proved to be full of surprised. The following differing situations were observed (a) the anti-proliferative effect is due to the vector and the organometallic moiety does not improve the effects of the SERM, no matter what concentration is used. In particular, this is the case for the hydroxytamoxifen derivative bearing a CpRe(CO)3 group, which behaves almost identically to hydroxytamoxifen. These stable species have future promise for use with radionucleides of Re and Tc (b) the effect of the organometallic moiety counteracts the anti-estrogenic behaviour of the vector and leads to species with proliferative activity; this is the case with Cp2TiCl2 entity, which when attached to tamoxifen behaves as a powerful estrogen, probably due to in situ release of Ti(IV) (c) a synergy exists between the cytotoxic organometallic moiety and its organic vector, leading to unique anti-proliferative effects on breast cancer cells classed ER+ and ER-. This result opens a new window on organometallic oncology. It is also clear that the range of possibilities is broad, varied and currently unpredictable. A systematic study combining organometallic chemistry and biology is the only option in the search for new SERMs with novel properties.
Keywords: bioorganometallic chemistry, ferrocene, metallocene, breast cancer, tamoxifen, serm
Current Medicinal Chemistry
Title: The First Organometallic Selective Estrogen Receptor Modulators (SERMs) and Their Relevance to Breast Cancer
Volume: 11 Issue: 18
Author(s): Gerard Jaouen, Siden Top, Anne Vessieres, G. Leclercq and Michael J. McGlinchey
Affiliation:
Keywords: bioorganometallic chemistry, ferrocene, metallocene, breast cancer, tamoxifen, serm
Abstract: In the overall scheme of the future development of new drugs for the treatment of breast cancer, specially tamoxifen resistant tumours, we have explored the unprecedented use of organometallic SERMs. The initial idea is to enhance the efficacy of the current standard, i.e. tamoxifen, by modifying the structure through judicious incorporation of an organometallic moiety possessing novel properties. Results have been varied, justifying a systematic approach that has proved to be full of surprised. The following differing situations were observed (a) the anti-proliferative effect is due to the vector and the organometallic moiety does not improve the effects of the SERM, no matter what concentration is used. In particular, this is the case for the hydroxytamoxifen derivative bearing a CpRe(CO)3 group, which behaves almost identically to hydroxytamoxifen. These stable species have future promise for use with radionucleides of Re and Tc (b) the effect of the organometallic moiety counteracts the anti-estrogenic behaviour of the vector and leads to species with proliferative activity; this is the case with Cp2TiCl2 entity, which when attached to tamoxifen behaves as a powerful estrogen, probably due to in situ release of Ti(IV) (c) a synergy exists between the cytotoxic organometallic moiety and its organic vector, leading to unique anti-proliferative effects on breast cancer cells classed ER+ and ER-. This result opens a new window on organometallic oncology. It is also clear that the range of possibilities is broad, varied and currently unpredictable. A systematic study combining organometallic chemistry and biology is the only option in the search for new SERMs with novel properties.
Export Options
About this article
Cite this article as:
Jaouen Gerard, Top Siden, Vessieres Anne, Leclercq G. and McGlinchey J. Michael, The First Organometallic Selective Estrogen Receptor Modulators (SERMs) and Their Relevance to Breast Cancer, Current Medicinal Chemistry 2004; 11 (18) . https://dx.doi.org/10.2174/0929867043364487
DOI https://dx.doi.org/10.2174/0929867043364487 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
- Announcements
Related Articles
-
Ganoderma lucidum (Ling-zhi): The Impact of Chemistry on Biological Activity in Cancer
Current Bioactive Compounds Long-circulating Targeted Nanoparticles for Cancer Therapy
Current Nanoscience Personalizing HER2-Targeted Therapy in Metastatic Breast Cancer Beyond HER2 Status: What We Have Learned from Clinical Specimens
Current Pharmacogenomics and Personalized Medicine Recent Advances in Curcumin Nanocarriers for the Treatment of Different Types of Cancer with Special Emphasis on In Vitro Cytotoxicity and Cellular Uptake Studies
Nanoscience & Nanotechnology-Asia Selected Attributes of Polyphenols in Targeting Oxidative Stress in Cancer
Current Topics in Medicinal Chemistry Targeting Microtubules to Inhibit Angiogenesis and Disrupt Tumour Vasculature:Implications for Cancer Treatment
Current Cancer Drug Targets Estrogen, Immunity & Autoimmune Disease
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents Advances in Oncolytic Virus Therapy for Glioma
Recent Patents on CNS Drug Discovery (Discontinued) Cardioprotection by Targeting the Pool of Resident and Extracardiac Progenitors
Current Drug Targets 9-Hydroxyellipticine and Derivatives as Chemotherapy Agents
Mini-Reviews in Medicinal Chemistry Anti-Cytokine Therapeutics: History and Update
Current Pharmaceutical Design Development of Genomics-Based Gene Expression Signature Biomarkers in Oncology and Toxicology to Facilitate Drug Discovery and Translational Medicine
Current Bioinformatics Challenging the Current Approaches to Multiple Myeloma-Related Bone Disease: From Bisphosphonates to Target Therapy
Current Cancer Drug Targets Tumor Initiating Cells
Current Pharmaceutical Biotechnology SNAP-Tag Technology: A Powerful Tool for Site Specific Conjugation of Therapeutic and Imaging Agents
Current Pharmaceutical Design New Medical Strategies for Midgut Carcinoids
Anti-Cancer Agents in Medicinal Chemistry Biochemical Aspects of Nitric Oxide
Current Pharmaceutical Design An Update on Potential Molecular Mechanisms Underlying the Actions of Snake Venom L-amino Acid Oxidases (LAAOs)
Current Medicinal Chemistry Proliferation of Breast Cancer Cells: Regulation, Mediators, Targets for Therapy
Anti-Cancer Agents in Medicinal Chemistry Recurrence in Bladder Cancer: A Molecular Dead End?
Current Genomics