The Design of Orally Active Iron Chelators
Abstract
A bstract: It is now generally accepted that it is not possible to design iron(III)‐selective hexadentate chelators with high oral bioavailability. In order to achieve suitable levels of oral activity for the treatment of systemic iron overload either tridentate or bidentate molecules need to be investigated. There are a number of such molecules in clinical practice, including hydroxypyridin‐4‐ones, desferrithiocin analogues and bis‐hydroxyphenyltriazoles. The underlying chemistry of each group is described, together with an indication of the distribution properties, redox cycling activity, and iron scavenging activity.
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It is not easy to make hexadentate ligands orally active.
“However, it is not easy to make hexadentate ligands orally active [1665].”
From Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases (2009) · cites this paper as [1665]
Bidentate or tridentate chelators that bind only 2 or 3 of the available iron chelation sites, especially when they bind both Fe(II) and Fe(III), can catalyse redox cycling and promote free radical generation.
“By contrast, bidentate or tridentate chelators that bind to only 2 or 3 of the available iron chelation sites, especially when they bind to both Fe(II) and Fe(III), can in fact catalyse redox cycling and thereby promote free radical generation [1437,1665,1670,1671].”
From Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases (2009) · cites this paper as [1665]
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- Authors
- HIDER, R. C., & ZHOU, T.
- Affiliations
- King's College London (GB)
- Corresponding author
- HIDER, ROBERT C.
- Venue
- Annals of the New York Academy of Sciences
- Publisher
- Wiley
- Published
- 2005-11
- Volume
- 1054
- Issue
- 1
- Pages
- 141-154
- ISSN
- 0077-8923 (ISSN-L)
- 1749-6632
- OpenAlex
- W2007680457
- Cited by
- 64
- References
- 19
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 1 · 2021: 3 · 2020: 4 · 2019: 3 · 2017: 3 · 2016: 3 · 2015: 2 · 2013: 4 · 2012: 2
- FWCI
- 2.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of the New York Academy of Sciences (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK057645, DK57645-01)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Oncology › Metal complexes synthesis and properties
- Physical Sciences › Chemistry › Organic Chemistry › Inorganic and Organometallic Chemistry
- Keywords
- iron chelators, oral bioavailability, redox cycling, iron scavenging, drug distribution
- MeSH terms
- Deferasirox, Administration, Oral, Benzoates, Clinical Trials as Topic, Dihydropyridines, Drug Evaluation, Preclinical, Humans, Iron, Iron Chelating Agents, Ligands, Models, Molecular, Oxidation-Reduction, Pyridones, Thiazoles, Triazoles, Drug Design, Molecular Structure
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