Abstract
The chelator currently used to treat iron (Fe) overload disease, desferrioxamine (DFO), has shown anti-proliferative activity against leukemia and neuroblastoma cells in vitro, in vivo and in clinical trials. Collectively, these studies suggest that Fe-deprivation may be a useful anti-cancer strategy. However, the efficacy of DFO is severely limited due to its poor ability to permeate cell membranes and bind intracellular Fe pools. These limitations have encouraged the development of other Fe chelators that are far more effective than DFO. One group of ligands that have been extensively investigated are those of the pyridoxal isonicotinoyl hydrazone (PIH) class. In this review the marked anti-proliferative effects of the PIH analogs are discussed with reference to their mechanisms of action and structure-activity relationships. In particular, we discuss the activity of a novel group of ligands that are “hybrid” chelators derived from our most effective PIH analogs and thiosemicarbazones. The anti-tumor activity of the PIH analogs and other chelators such as tachpyridine, O-trensox and the desferrithiocin analogs have been well characterized in vitro. However, further studies in animals are critical to evaluate their selective anti-tumor activity and potential as therapeutic agents.
Keywords: cancer, desferrioxamine, iron chelators, iron metabolism, pyridoxal isonicotinoyl hydrazone
Current Medicinal Chemistry
Title: Iron Chelators as Anti-Neoplastic Agents: Current Developments and Promise of the PIH Class of Chelators
Volume: 10 Issue: 12
Author(s): D. B. Lovejoy and D. R. Richardson
Affiliation:
Keywords: cancer, desferrioxamine, iron chelators, iron metabolism, pyridoxal isonicotinoyl hydrazone
Abstract: The chelator currently used to treat iron (Fe) overload disease, desferrioxamine (DFO), has shown anti-proliferative activity against leukemia and neuroblastoma cells in vitro, in vivo and in clinical trials. Collectively, these studies suggest that Fe-deprivation may be a useful anti-cancer strategy. However, the efficacy of DFO is severely limited due to its poor ability to permeate cell membranes and bind intracellular Fe pools. These limitations have encouraged the development of other Fe chelators that are far more effective than DFO. One group of ligands that have been extensively investigated are those of the pyridoxal isonicotinoyl hydrazone (PIH) class. In this review the marked anti-proliferative effects of the PIH analogs are discussed with reference to their mechanisms of action and structure-activity relationships. In particular, we discuss the activity of a novel group of ligands that are “hybrid” chelators derived from our most effective PIH analogs and thiosemicarbazones. The anti-tumor activity of the PIH analogs and other chelators such as tachpyridine, O-trensox and the desferrithiocin analogs have been well characterized in vitro. However, further studies in animals are critical to evaluate their selective anti-tumor activity and potential as therapeutic agents.
Export Options
About this article
Cite this article as:
Lovejoy B. D. and Richardson R. D., Iron Chelators as Anti-Neoplastic Agents: Current Developments and Promise of the PIH Class of Chelators, Current Medicinal Chemistry 2003; 10 (12) . https://dx.doi.org/10.2174/0929867033457557
DOI https://dx.doi.org/10.2174/0929867033457557 |
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
-
Survivin Modulators: An Updated Patent Review (2011 - 2015)
Recent Patents on Anti-Cancer Drug Discovery Recent Advances and Approaches in Targeting Apoptosis Signaling Pathways for Anti-Cancer Therapeutics
Current Cancer Therapy Reviews Promoters and Control Elements: Designing Expression Cassettes for Gene Therapy
Current Gene Therapy Novel Multifunctional Anti-Alzheimer Drugs with Various CNS Neurotransmitter Targets and Neuroprotective Moieties
Current Alzheimer Research MicroRNAs in Cancer Therapy: From Bench to Bedside
Current Cancer Therapy Reviews Glycosaminoglycans, Protein Aggregation and Neurodegeneration
Current Protein & Peptide Science Chemokines and Brain Functions
Current Drug Targets - Inflammation & Allergy Novel Anticancer Agents and Targets: Recent Advances and Future Perspectives
Mini-Reviews in Medicinal Chemistry Quinone-Based Drugs: An Important Class of Molecules in Medicinal Chemistry
Medicinal Chemistry The Role of Downstream Signaling Pathways of the Epidermal Growth Factor Receptor for Artesunates Activity in Cancer Cells
Current Cancer Drug Targets Aurora Kinase Inhibitors in Head and Neck Cancer
Current Topics in Medicinal Chemistry Neurotrophic Factor Treatment After Spinal Root Avulsion Injury
Central Nervous System Agents in Medicinal Chemistry Interaction of ABC Multidrug Transporters with Anticancer Protein Kinase Inhibitors: Substrates and/or Inhibitors?
Current Cancer Drug Targets Targeting Parkinson’s - Tyrosine Hydroxylase and Oxidative Stress as Points of Interventions
CNS & Neurological Disorders - Drug Targets Boron Nitride Nanotubes: Production, Properties, Biological Interactions and Potential Applications as Therapeutic Agents in Brain Diseases
Current Nanoscience Connections Between Herpes Simplex Virus Type 1 and Alzheimer's Disease Pathogenesis
Current Alzheimer Research Impaired Quality Control of Mitochondria Underlying the Pathogenesis of Alzheimer's Disease
Current Drug Targets Imaging Adoptive Cell Transfer Based Cancer Immunotherapy
Current Pharmaceutical Biotechnology HCV Infection by Cell-to-Cell Transmission: Choice or Necessity?
Current Molecular Medicine The Path from Anti Parkinson Drug Selegiline and Rasagiline to Multifunctional Neuroprotective Anti Alzheimer Drugs Ladostigil and M30
Current Alzheimer Research