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
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
-
Review on Patents for Ubiquitin-Proteasome Inhibitor as Medical Advance in Major Human Diseases
Recent Patents on Biomedical Engineering (Discontinued) Resistance to Diuretics in Heart Failure: Any Role for Empagliflozin?
Current Vascular Pharmacology Monoclonal Antibody-Based Targeted Therapy in Breast Cancer
Current Medicinal Chemistry - Anti-Cancer Agents Aspartic Protease Inhibitors as Potential Anti-Candida albicans Drugs: Impacts on Fungal Biology, Virulence and Pathogenesis
Current Medicinal Chemistry Minimally-invasive LVAD Implantation: State of the Art
Current Cardiology Reviews Do Advanced Glycation End Products (AGEs) Contribute to the Comorbidities of Polycystic Ovary Syndrome (PCOS)?
Current Pharmaceutical Design Insulin Therapy in Cardiac Surgery
Current Diabetes Reviews Adrenergic Drugs Blockers or Enhancers for Cognitive Decline ? What to Choose for Alzheimer’s Disease Patients?
CNS & Neurological Disorders - Drug Targets Flavonoid-Based Cancer Therapy: An Updated Review
Anti-Cancer Agents in Medicinal Chemistry Mini Heme-Proteins: Designability of Structure and Diversity of Functions
Current Protein & Peptide Science Clinical Trials Using Vasodilators in Pulmonary Arterial Hypertension:Where Do We Go from Here?
Reviews on Recent Clinical Trials Medicinal Plants Towards Modeling Skin Cancer
Current Drug Targets Cardiac Biomarkers in the Identification of Future Risk in Chronic Obstructive Pulmonary Disease
Current Topics in Medicinal Chemistry Device-based Therapies for Resistant Hypertension
Current Pharmaceutical Design Medical Management of the Diabetic Patient with Coronary Artery Disease
Current Pharmaceutical Design Inhibition of IκB Phosphorylation by a Novel IKK Inhibitor IMD-1041 Attenuates Myocardial Dysfunction After Infarction
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Calcium Channel Blockers in Obesity-Related Hypertension
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) The Relationship between Inflammatory and Oxidative Stress Biomarkers, Atherosclerosis and Rheumatic Diseases
Current Pharmaceutical Design Remodeling of Protein Aggregates by Hsp104
Protein & Peptide Letters The Role of Insertion Allele of Angiotensin Converting Enzyme Gene in Higher Endurance Efficiency and Some Aspects of Pathophysiological and Drug Effects
Current Medicinal Chemistry