Abstract
Arsenic trioxide appears to be effective in the treatment of pro-myelocytic leukaemia. The substituted phenylarsen(III)oxides are highly polar, they have a high tendency to undergo oxidation to As (V) and to form oligomers, to prevent this we protected the As-(OH)2 group as cyclic dithiaarsanes. To increase the compounds biological stability and passive diffusion we conjugated the compound of interest with lipoamino acids (Laas). Alternatively, we further conjugated the dithiaarsane derivative with a carbohydrate to utilize active transport systems and to target compound. We investigated two novel glyco-lipid arsenicals (III) (compounds 9 and 11) for their ability to initiate MCF-7 breast cancer cell death and characterized the mechanism by which death was initiated. A significant decrease in MCF-7 cell proliferation was observed using 1 μM and 10 μM compound (11) and 10 μM of compound (9). Treatment with compound (11) triggered apoptosis of MFC-7 cells while compound (9) induced inhibition of cellular proliferation was not via rapid induction of apoptosis and more likely reflected necrosis and/or alterations in the cell cycle. Differences in the anti-proliferative potency of the two compounds indicate that structural modifications influence effectiveness.
Keywords: Arsenicals, trivalent, trivalent organoarsenicals, Lipoaminoacid (Laa), chemotherapeutics
Medicinal Chemistry
Title: Anti-Proliferative Effects of Novel Glyco-Lipid-Arsenicals (III) on MCF-7 Human Breast Cancer Cells
Volume: 2 Issue: 1
Author(s): Norbert Wimmer, Jodie A. Robinson, Nagaraj Gopisetty-Venkata, Sarah J. Roberts-Thomson, Gregory R. Monteith and Istvan Toth
Affiliation:
Keywords: Arsenicals, trivalent, trivalent organoarsenicals, Lipoaminoacid (Laa), chemotherapeutics
Abstract: Arsenic trioxide appears to be effective in the treatment of pro-myelocytic leukaemia. The substituted phenylarsen(III)oxides are highly polar, they have a high tendency to undergo oxidation to As (V) and to form oligomers, to prevent this we protected the As-(OH)2 group as cyclic dithiaarsanes. To increase the compounds biological stability and passive diffusion we conjugated the compound of interest with lipoamino acids (Laas). Alternatively, we further conjugated the dithiaarsane derivative with a carbohydrate to utilize active transport systems and to target compound. We investigated two novel glyco-lipid arsenicals (III) (compounds 9 and 11) for their ability to initiate MCF-7 breast cancer cell death and characterized the mechanism by which death was initiated. A significant decrease in MCF-7 cell proliferation was observed using 1 μM and 10 μM compound (11) and 10 μM of compound (9). Treatment with compound (11) triggered apoptosis of MFC-7 cells while compound (9) induced inhibition of cellular proliferation was not via rapid induction of apoptosis and more likely reflected necrosis and/or alterations in the cell cycle. Differences in the anti-proliferative potency of the two compounds indicate that structural modifications influence effectiveness.
Export Options
About this article
Cite this article as:
Wimmer Norbert, Robinson A. Jodie, Gopisetty-Venkata Nagaraj, Roberts-Thomson J. Sarah, Monteith R. Gregory and Toth Istvan, Anti-Proliferative Effects of Novel Glyco-Lipid-Arsenicals (III) on MCF-7 Human Breast Cancer Cells, Medicinal Chemistry 2006; 2 (1) . https://dx.doi.org/10.2174/157340606775197714
DOI https://dx.doi.org/10.2174/157340606775197714 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
Call for Papers in Thematic Issues
Carbohydrates in Computational and Medicinal Chemistry
Carbohydrates are the most essential organic molecules and are involved in the maintenance of various physiological and metabolic processes in living organisms. Carbohydrate-based compounds have come to the attention of researchers because of their significant contributions to biological functions, such as cell development and cell proliferation, connections between several cells, ...read more
Recent Advances in the Medicinal Chemistry of Cancer
Scope of the Thematic Issue: Correlation between structure and function is one of the important aspects of the success of anti-cancer compounds associated with their structure-activity interactions, physiology, biochemical, molecular, and genetic processes. Overcoming these obstacles is key to obtaining further insights into developments in rational drug design, bioorganic chemistry, ...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
-
Biological Drugs in Guillain-Barré Syndrome: An Update
Current Neuropharmacology 1,3,4-Oxadiazole Derivatives as Potential Biological Agents
Mini-Reviews in Medicinal Chemistry Pathophysiological and Clinical Aspects of Iron Chelation Therapy in MDS
Current Pharmaceutical Design Fused Xanthone Derivatives as Antiproliferative Agents
Anti-Cancer Agents in Medicinal Chemistry Neuroimaging Features of Acquired Metabolic and Toxic Encephalopathies
Current Medical Imaging Pyrimethamine as a Potent and Selective Inhibitor of Acute Myeloid Leukemia Identified by High-throughput Drug Screening
Current Cancer Drug Targets Bench to Bedside Targeting of FLT3 in Acute Leukemia
Current Drug Targets Characterization of the Early CNS Stress Biomarkers and Profiles Associated with Neuropsychiatric Diseases
Current Genomics Resveratrol and Neurodegenerative Diseases: Activation of SIRT1 as the Potential Pathway towards Neuroprotection
Current Neurovascular Research Quinone-Based Drugs: An Important Class of Molecules in Medicinal Chemistry
Medicinal Chemistry Alternatives to Conventional Vaccines - Mediators of Innate Immunity
Current Drug Targets Repositioning of DHFR Inhibitors
Current Topics in Medicinal Chemistry Measurement of Vitamin K Metabolites in Neonatal Faecal Matter by HPLC with Electrochemical Detection
Current Chromatography New Strategies in the Chemotherapy of Leukemia: Eradicating Cancer Stem Cells in Chronic Myeloid Leukemia
Current Cancer Drug Targets Genes Associated with Epithelial-Mesenchymal Transition: Possible Therapeutic Targets in Ductal Pancreatic Adenocarcinoma?
Anti-Cancer Agents in Medicinal Chemistry Development of Decision Tree Models for Substrates, Inhibitors, and Inducers of P-Glycoprotein
Current Drug Metabolism The 18 kDa Translocator Protein (TSPO): A New Perspective in Mitochondrial Biology
Current Molecular Medicine Vitamin D and Lung Cancer
Current Respiratory Medicine Reviews Potential Gene Therapy Strategies for Cancer Stem Cells
Current Gene Therapy Monoclonal Antibodies: New Therapeutic Agents for Autoimmune Hemolytic Anemia?
Endocrine, Metabolic & Immune Disorders - Drug Targets