Abstract
Iron chelators may be of value as therapeutic agents in the treatment of cancer. They may act by depleting iron, a necessary nutrient, and limiting tumor growth. Alternatively or additionally, they may form redox-active metal complexes that cause oxidative stress via production of reactive oxygen species, damaging critical intracellular targets and thereby eliciting a cytotoxic response. Studies in vitro have evaluated the structure-activity relationships and mechanism of action of many classes of iron chelators, including desferrioxamine (DFO), pyridoxal isonicotinoyl hydrazone (PIH) analogs, desferrithiocin (DFT) analogs, tachpyridine, the heterocyclic carboxaldehyde thiosemicarbazones, and OTrensox. Animal studies have confirmed the antitumor activity of several chelators. Dexrazoxane has been approved for use in combination with doxorubicin, and its effectiveness in allowing higher doses of doxorubicin to be administered is, in part, based on the interactions of both drugs with iron. Clinical trials of the antitumor activity of chelators have been largely limited to DFO, which has been extensively studied as a consequence of its approved use for treatment of secondary iron overload. While the modest antitumor effects of DFO are encouraging, it is likely that more effective iron chelators may be identified
Keywords: apoptosis, cytotoxicity, drug design, ribonucleotide reductase, desferrioxamine, iron depletion, cell cycle, cancer
Current Topics in Medicinal Chemistry
Title: Iron Chelators in Cancer Chemotherapy
Volume: 4 Issue: 15
Author(s): Joan L. Buss, Bryan T. Greene, JoLyn Turner, Frank M. Torti and Suzy V. Torti
Affiliation:
Keywords: apoptosis, cytotoxicity, drug design, ribonucleotide reductase, desferrioxamine, iron depletion, cell cycle, cancer
Abstract: Iron chelators may be of value as therapeutic agents in the treatment of cancer. They may act by depleting iron, a necessary nutrient, and limiting tumor growth. Alternatively or additionally, they may form redox-active metal complexes that cause oxidative stress via production of reactive oxygen species, damaging critical intracellular targets and thereby eliciting a cytotoxic response. Studies in vitro have evaluated the structure-activity relationships and mechanism of action of many classes of iron chelators, including desferrioxamine (DFO), pyridoxal isonicotinoyl hydrazone (PIH) analogs, desferrithiocin (DFT) analogs, tachpyridine, the heterocyclic carboxaldehyde thiosemicarbazones, and OTrensox. Animal studies have confirmed the antitumor activity of several chelators. Dexrazoxane has been approved for use in combination with doxorubicin, and its effectiveness in allowing higher doses of doxorubicin to be administered is, in part, based on the interactions of both drugs with iron. Clinical trials of the antitumor activity of chelators have been largely limited to DFO, which has been extensively studied as a consequence of its approved use for treatment of secondary iron overload. While the modest antitumor effects of DFO are encouraging, it is likely that more effective iron chelators may be identified
Export Options
About this article
Cite this article as:
Joan L. Buss , Bryan T. Greene , JoLyn Turner , Frank M. Torti and Suzy V. Torti , Iron Chelators in Cancer Chemotherapy, Current Topics in Medicinal Chemistry 2004; 4 (15) . https://dx.doi.org/10.2174/1568026043387269
DOI https://dx.doi.org/10.2174/1568026043387269 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Medicinal Chemistry Advancement in Life-Threatening Diseases
The current issue will highlight concise reports that specify ground-breaking insights, including the novel discovery of drug targets and their action mechanism or drugs of novel classes. These are projected to encourage medicinal chemistry future efforts to address the most challenging medical needs. The current issue highlights further efforts to ...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
-
Glucose Control and Use of Continuous Glucose Monitoring in the Intensive Care Unit: A Critical Review
Current Diabetes Reviews Hypertension in Diabetes: Optimal Pharmacotherapy
Cardiovascular & Hematological Agents in Medicinal Chemistry SUMOylation in Neurological Diseases
Current Molecular Medicine Pulmonary Hemorrhage in Patients with Systemic Lupus Erythematosus
Current Respiratory Medicine Reviews Pharmacological Properties and Therapeutic Possibilities for Drugs Acting Upon Endocannabinoid Receptors
Current Drug Targets - CNS & Neurological Disorders Signal Proteins Involved in Myogenic Stem Cells Differentiation
Current Protein & Peptide Science microRNA as Biomarkers and Regulator of Cardiovascular Development and Disease
Current Pharmaceutical Design Phenotypes and Enviromental Factors: Their Influence in PCOS
Current Pharmaceutical Design Humic Acids as Therapeutic Compounds in Lead Intoxication
Current Clinical Pharmacology Editorial (Hot Topic: Platelets in Vascular Homeostasis and Inflammation: Current Perspectives from Bench to Bedside)
Current Vascular Pharmacology Patents on Technologies of Human Tissue and Organ Regeneration from Pluripotent Human Embryonic Stem Cells
Recent Patents on Regenerative Medicine Emerging Strategies and Challenges for Controlled Delivery of Taxanes: A Comprehensive Review
Current Drug Metabolism Survey of Mortality Due to Influenza A in North of Iran, 2015-2016
Current Respiratory Medicine Reviews Mechanism-Based Inhibitors from Phytomedicine: Risks of Hepatotoxicity and their Potential Hepatotoxic Substructures
Current Drug Metabolism Silent Partner in Blood Vessel Homeostasis? Pervasive Role of Nitric Oxide in Vascular Disease
Current Hypertension Reviews Inflammatory Mechanisms in Atherosclerosis: The Impact of Matrix Metalloproteinases
Current Topics in Medicinal Chemistry The Boundary between Hypochondriasis, Personality Dysfunction, and Trauma
Current Psychiatry Reviews Novel Classes of Dimer Antitumour Drug Candidates
Current Pharmaceutical Design Effects of Altered Plasminogen Activator Inhibitor-1 Expression on Cardiovascular Disease
Current Drug Targets NGAL is a Precocious Marker of Therapeutic Response
Current Pharmaceutical Design