Synthetic and natural iron chelators: Therapeutic potential and clinical use
Open accessAbstract
Iron-chelation therapy has its origins in the treatment of iron-overload syndromes. For many years, the standard for this purpose has been deferoxamine. Recently, considerable progress has been made in identifying synthetic chelators with improved pharmacologic properties relative to deferoxamine. Most notable are deferasirox (Exjade(®)) and deferiprone (Ferriprox(®)), which are now available clinically. In addition to treatment of iron overload, there is an emerging role for iron chelators in the treatment of diseases characterized by oxidative stress, including cardiovascular disease, atherosclerosis, neurodegenerative diseases and cancer. While iron is not regarded as the underlying cause of these diseases, it does play an important role in disease progression, either through promotion of cellular growth and proliferation or through participation in redox reactions that catalyze the formation of reactive oxygen species and increase oxidative stress. Thus, iron chelators may be of therapeutic benefit in many of these conditions. Phytochemicals, many of which bind iron, may also owe some of their beneficial properties to iron chelation. This review will focus on the advances in iron-chelation therapy for the treatment of iron-overload disease and cancer, as well as neurodegenerative and chronic inflammatory diseases. Established and novel iron chelators will be discussed, as well as the emerging role of dietary plant polyphenols that effectively modulate iron biochemistry.
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The natural siderophore desferrioxamine (DFO) as well as the synthetic chelator derasirox (DFX) and the thiosemicarbazone Triapine have shown promising anti-cancer activity in clinical trials.
“For instance, the natural siderophore desferrioxamine (DFO, Desferal®) [134,135] as well as the synthetic chelator derasirox (DFX, Exiade), which are clinically employed to treat iron overload due to chronic blood transfusion therapy [134], and the thiosemicarbazone Triapine® [136,137] have shown promising anti-cancer activity in clinical trials [138].”
From Iron as a central player and promising target in cancer progression (2019) · cites this paper as [138]
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- [121]Yang LP Keam SJ Keating GM Deferasirox: a review of its use in the management of transfusional chronic iron overload Drugs 2007 67 2211 2230 17927285
- [200]Youdim KA McDonald J Kalt W Joseph JA Potential role of dietary flavonoids in reducing microvascular endothelium vulnerability to oxidative and inflammatory insults (small star, filled) J. Nutr. Biochem 2002 13 282 288 12015158
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Iron and cancer: more ore to be mined
Torti, S. V., & Torti, F. M. (2013) · Nature Reviews Cancer · doi:10.1038/nrc3495 · Cited by 1,621 · see citing works
Hoes, M. F., Grote Beverborg, N., Kijlstra, J. D., Kuipers, J., Swinkels, D. W., Giepmans, B. N. G., Rodenburg, R. J., van Veldhuisen, D. J., de Boer, R. A., & van der Meer, P. (2018) · European Journal of Heart Failure · doi:10.1002/ejhf.1154 · Cited by 333 · see citing works
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Use of polyphenol-rich grape by-products in monogastric nutrition. A review
Brenes, A., Viveros, A., Chamorro, S., & Arija, I. (2015) · Animal Feed Science and Technology · doi:10.1016/j.anifeedsci.2015.09.016 · Cited by 321 · see citing works
Iron as a central player and promising target in cancer progression
Jung, M., Mertens, C., Tomat, E., & Brüne, B. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20020273 · Cited by 268 · see citing works
“For instance, the natural siderophore desferrioxamine (DFO, Desferal®) [134,135] as well as the synthetic chelator derasirox (DFX, Exiade), which are clinically employed to treat iron overload due to chronic blood transfusion therapy [134], and the thiosemicarbazone Triapine® [136,137] have shown promising anti-cancer…”
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The role of lysosomes in iron metabolism and recycling
Kurz, T., Eaton, J. W., & Brunk, U. T. (2011) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2011.08.016 · Cited by 207 · see citing works
Redox Imbalance in Inflammation: The Interplay of Oxidative and Reductive Stress
Bellanti, F., Coda, A. R. D., Trecca, M. I., Buglio, A. L., Serviddio, G., & Vendemiale, G. (2025) · Antioxidants · doi:10.3390/antiox14060656 · Cited by 212 · see citing works
Macciò, A., Gramignano, G., Cherchi, M. C., Tanca, L., Melis, L., & Madeddu, C. (2020) · Scientific Reports · doi:10.1038/s41598-020-63276-1 · Cited by 182 · see citing works
Deferoxamine B: A Natural, Excellent and Versatile Metal Chelator
Bellotti, D., & Remelli, M. (2021) · Molecules · doi:10.3390/molecules26113255 · Cited by 152 · see citing works
Farr, A. C., & Xiong, M. P. (2020) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.0c00474 · Cited by 149 · see citing works
Restored iron transport by a small molecule promotes absorption and hemoglobinization in animals
Grillo, A. S., SantaMaria, A. M., Kafina, M. D., Cioffi, A. G., Huston, N. C., Han, M., Seo, Y. A., Yien, Y. Y., Nardone, C., Menon, A. V., et al. (2017) · Science · doi:10.1126/science.aah3862 · Cited by 147 · see citing works
Deferoxamine: An Angiogenic and Antioxidant Molecule for Tissue Regeneration
Holden, P., & Nair, L. S. (2019) · Tissue Engineering Part B Reviews · doi:10.1089/ten.teb.2019.0111 · Cited by 128 · see citing works
The Chelating Ability of Plant Polyphenols Can Affect Iron Homeostasis and Gut Microbiota
Scarano, A., Laddomada, B., Blando, F., Santis, S. D., Verna, G., Chieppa, M., & Santino, A. (2023) · Antioxidants · doi:10.3390/antiox12030630 · Cited by 130 · see citing works
Nath, H., Samtiya, M., & Dhewa, T. (2022) · Human Nutrition & Metabolism · doi:10.1016/j.hnm.2022.200147 · Cited by 124 · see citing works
The Role of Iron, Its Metabolism and Ferroptosis in Traumatic Brain Injury
Tang, S., Gao, P., Chen, H., Zhou, X., Ou, Y., & He, Y. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.590789 · Cited by 119 · see citing works
Biophysical and in vitro absorption studies of iron chelating peptide from barley proteins
Eckert, E., Lu, L., Unsworth, L. D., Chen, L., Xie, J., & Xu, R. (2016) · Journal of Functional Foods · doi:10.1016/j.jff.2016.06.011 · Cited by 108 · see citing works
Quercetin attenuates neurotoxicity induced by iron oxide nanoparticles
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Advances in iron chelation: an update
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Mertens, C., Akam, E. A., Rehwald, C., Brüne, B., Tomat, E., & Jung, M. (2016) · PLOS ONE · doi:10.1371/journal.pone.0166164 · Cited by 83 · see citing works
Hypoxia Mimetic Agents for Ischemic Stroke
Davis, C. K., Jain, S. A., Bae, O., Majid, A., & Rajanikant, G. K. (2019) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2018.00175 · Cited by 80 · see citing works
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Proanthocyanidin promotes functional recovery of spinal cord injury via inhibiting ferroptosis
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Recent advances in cancer treatment by iron chelators
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Role of Carbon Monoxide in Host–Gut Microbiome Communication
Hopper, C., Cruz, L. K. D. L., Lyles, K. V. M., Wareham, L. K., Gilbert, J. A., Eichenbaum, Z., Magierowski, M., Poole, R. K., Wollborn, J., & Wang, B. (2020) · Chemical Reviews · doi:10.1021/acs.chemrev.0c00586 · Cited by 72 · see citing works
Parkinson’s Disease: The Mitochondria-Iron Link
Muñoz, Y., Carrasco, C. M., Campos, J., Aguirre, P., & Núñez, M. T. (2016) · Parkinson s Disease · doi:10.1155/2016/7049108 · Cited by 73 · see citing works
Iron chelators in cancer therapy
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Singh, Y. P., Pandey, A., Vishwakarma, S., & Modi, G. P. (2018) · Molecular Diversity · doi:10.1007/s11030-018-9878-4 · Cited by 67 · see citing works
Tannic acid (TA): A molecular tool for chelating and imaging labile iron
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Mostajeran, M., Bondy, J.-M., Reynier, N., & Cameron, R. A. (2021) · Minerals Engineering · doi:10.1016/j.mineng.2021.107091 · Cited by 63 · see citing works
Natural Antioxidants in Anemia Treatment
Cotoraci, C. A., Ciceu, A., Sasu, A., & Hermenean, A. O. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22041883 · Cited by 69 · see citing works
Lipocalin-2 and iron trafficking in the tumor microenvironment
Jung, M., Mertens, C., Bauer, R., Rehwald, C., & Brüne, B. (2017) · Pharmacological Research · doi:10.1016/j.phrs.2017.03.018 · Cited by 60 · see citing works
Targeting ferroptosis in ischemia/reperfusion renal injury
Thapa, K., Singh, T. G., & Kaur, A. (2022) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-022-02277-5 · Cited by 60 · see citing works
Ferroptosis in acute kidney injury following crush syndrome: A novel target for treatment
Qiao, O., Wang, X., Wang, Y., Li, N., & Gong, Y. (2023) · Journal of Advanced Research · doi:10.1016/j.jare.2023.01.016 · Cited by 60 · see citing works
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Shedding a New Light on Skin Aging, Iron- and Redox-Homeostasis and Emerging Natural Antioxidants
Pourzand, C., Albieri, A., & Raczek, N. N. (2022) · Antioxidants · doi:10.3390/antiox11030471 · Cited by 62 · see citing works
Moayedi, B., Gharagozloo, M., Esmaeil, N., Maracy, M. R., Hoorfar, H., & Jalaeikar, M. (2012) · European Journal Of Haematology · doi:10.1111/ejh.12061 · Cited by 59 · see citing works
Quercetin as a shuttle for labile iron
Baccan, M. M., Chiarelli-Neto, O., Pereira, R. M. S., & Espósito, B. P. (2011) · Journal of Inorganic Biochemistry · doi:10.1016/j.jinorgbio.2011.11.014 · Cited by 59 · see citing works
Saxon, E., & Peng, X. (2021) · ChemBioChem · doi:10.1002/cbic.202100366 · Cited by 57 · see citing works
Therapeutic potential of iron chelators on osteoporosis and their cellular mechanisms
Zhang, J., Zhao, H., Yao, G., Qiao, P., Li, L., & Wu, S. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.111380 · Cited by 56 · see citing works
Zahirović, A., Fetahović, S., Feizi‐Dehnayebi, M., Bešta‐Gajević, R., Dizdar, M., Ostojić, J., & Roca, S. (2024) · Journal of Molecular Structure · doi:10.1016/j.molstruc.2024.138628 · Cited by 56 · see citing works
Hydroxypyridinone-Based Iron Chelators with Broad-Ranging Biological Activities
Jiang, X., Zhou, T., Bai, R., & Xie, Y. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01480 · Cited by 54 · see citing works
Dysregulation of iron metabolism in cardiovascular diseases: From iron deficiency to iron overload
Bi, Y., Ajoolabady, A., Demillard, L. J., Yu, W., Hilaire, M. L., Zhang, Y., & Ren, J. T. (2021) · Biochemical Pharmacology · doi:10.1016/j.bcp.2021.114661 · Cited by 54 · see citing works
Ultraviolet Light Protection: Is It Really Enough?
Farris, P. K., & Valacchi, G. (2022) · Antioxidants · doi:10.3390/antiox11081484 · Cited by 55 · see citing works
Bhowmik, A., Ojha, D., Goswami, D., Das, R., Chandra, N. S., Chatterjee, T. K., Chakravarty, A., Chakravarty, S., & Chattopadhyay, D. (2017) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2016.12.125 · Cited by 53 · see citing works
van Rensburg, Z. J., Abrahams, S., Bardien, S., & Kenyon, C. P. (2021) · Molecular Neurobiology · doi:10.1007/s12035-021-02516-5 · Cited by 51 · see citing works
Turchini, G. M., Francis, D. S., Du, Z., Olsen, R. E., Ringø, E., & Tocher, D. R. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-819587-1.00003-3 · Cited by 50 · see citing works
Iron Pathways and Iron Chelation Approaches in Viral, Microbial, and Fungal Infections
Chhabra, R., Saha, A., Chamani, A., Schneider, N., Shah, R., & Nanjundan, M. (2020) · Pharmaceuticals · doi:10.3390/ph13100275 · Cited by 51 · see citing works
Chelation in Antibacterial Drugs: From Nitroxoline to Cefiderocol and Beyond
Antić, D. R., Parčina, M., Gobin, I., & Didović, M. P. (2022) · Antibiotics · doi:10.3390/antibiotics11081105 · Cited by 49 · see citing works
Elessawy, F. M., Vandenberg, A., El‐Aneed, A., & Purves, R. W. (2021) · Molecules · doi:10.3390/molecules26133833 · Cited by 49 · see citing works
Fedenko, V. S., Landi, M., & Shemet, S. A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231911370 · Cited by 50 · see citing works
Williams, C. L., Caraballo‐Rodríguez, A. M., Allaband, C., Zarrinpar, A., Knight, R. D., & Gauglitz, J. M. (2018) · Drug Discovery Today Disease Models · doi:10.1016/j.ddmod.2019.08.012 · Cited by 46 · see citing works
Iron–Sulfur Cluster Biogenesis as a Critical Target in Cancer
Petronek, M. S., Spitz, D. R., & Allen, B. G. (2021) · Antioxidants · doi:10.3390/antiox10091458 · Cited by 46 · see citing works
Deng, Z., Manz, D. H., Torti, S. V., & Torti, F. M. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7023 · Cited by 47 · see citing works
Advances in Hypoxia-Inducible Factor-1 α Stabilizer Deferoxamine in Tissue Engineering
Zhu, Y., Chang, B., Pang, Y., Wang, H., & Zhou, Y. (2022) · Tissue Engineering Part B Reviews · doi:10.1089/ten.teb.2022.0168 · Cited by 46 · see citing works
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Dendritic Cells Modulate Iron Homeostasis and Inflammatory Abilities Following Quercetin Exposure
Galleggiante, V., Santis, S. D., Cavalcanti, E., Scarano, A., Benedictis, M. D., Serino, G., Caruso, M. L., Mastronardi, M., Pinto, A., Campiglia, P., et al. (2017) · Current Pharmaceutical Design · doi:10.2174/1381612823666170112125355 · Cited by 44 · see citing works
Combating Iron Overload: A Case for Deferoxamine-Based Nanochelators
Jones, G., Goswami, S. K., Kang, H., Choi, H. S., & Kim, J. (2020) · Nanomedicine · doi:10.2217/nnm-2020-0038 · Cited by 45 · see citing works
Broadening horizons: ferroptosis as a new target for traumatic brain injury
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Effect of the oral iron chelator deferiprone in diabetic nephropathy rats
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Lysosomal targeting strategies for design and delivery of bioactive for therapeutic interventions
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Iron Chelators with Topoisomerase-Inhibitory Activity and Their Anticancer Applications
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Ethylene, an early marker of systemic inflammation in humans
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Up-regulation of hypoxia-inducible factor antisense as a novel approach to treat ovarian cancer
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Proteomic profiling reveals that collismycin A is an iron chelator
Kawatani, M., Muroi, M., Wada, A., Inoue, G., Futamura, Y., Aono, H., Shimizu, K., Shimizu, T., Igarashi, Y., Takahashi, N., et al. (2016) · Scientific Reports · doi:10.1038/srep38385 · Cited by 36 · see citing works
Structural Basis for Xenosiderophore Utilization by the Human Pathogen Staphylococcus aureus
Endicott, N. P., Lee, E., & Wencewicz, T. A. (2017) · ACS Infectious Diseases · doi:10.1021/acsinfecdis.7b00036 · Cited by 34 · see citing works
Application of Deferoxamine in Tissue Regeneration Attributed to Promoted Angiogenesis
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Iron limitation in M. tuberculosis has broad impact on central carbon metabolism
Theriault, M., Pisu, D., Wilburn, K. M., Lê-Bury, G., MacNamara, C. W., Petrassi, H., Love, M., Rock, J., VanderVen, B. C., & Russell, D. (2022) · Communications Biology · doi:10.1038/s42003-022-03650-z · Cited by 27 · see citing works
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Expression of Iron-Related Proteins Differentiate Non-Cancerous and Cancerous Breast Tumors
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The complex interplay between ferroptosis and atherosclerosis
Zhang, M., Li, J., & Hu, W. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.117183 · Cited by 31 · see citing works
Synthetic and semi-synthetic antioxidants in medicine and food industry: a review
Tauchen, J., Huml, L., Jurášek, M., Regenstein, J. M., & Özoğul, F. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1599816 · Cited by 31 · see citing works
Anti-inflammatory effects of a novel iron chelator, DIBI, in experimental sepsis
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Understanding the Potential and Risk of Bacterial Siderophores in Cancer
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The Role of Iron in Atherosclerosis and its Association with Related Diseases
Gao, Y., Wang, B., Hu, M., Ma, Y., & Zheng, B. (2024) · Current Atherosclerosis Reports · doi:10.1007/s11883-024-01251-1 · Cited by 25 · see citing works
Small Molecule Chelators Reveal That Iron Starvation Inhibits Late Stages of Bacterial Cytokinesis
Santos, T. M. A., Lammers, M. G., Zhou, M., Sparks, I. L., Rajendran, M., Fang, D., Jesus, C. L. Y. D., Carneiro, G. F. R., Cui, Q., & Weibel, D. B. (2017) · ACS Chemical Biology · doi:10.1021/acschembio.7b00560 · Cited by 25 · see citing works
Forging New Antibiotic Combinations under Iron-Limiting Conditions
Chan, D. C. K., Guo, I., & Burrows, L. L. (2020) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01909-19 · Cited by 24 · see citing works
Orfanou, I.-M., Argyros, O., Papapetropoulos, A., Tseleni‐Balafouta, S., Vougas, K. N., & Tamvakopoulos, C. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.608201 · Cited by 25 · see citing works
- Authors
- Hatcher, H. C., Singh, R. N., Torti, F. M., & Torti, S. V.
- Affiliations
- Wake Forest University Health Sciences (US)
- Department of Cancer Biology, Winston-Salem, NC, USA
- Corresponding author
- Torti, Suzy V
- Venue
- Future Medicinal Chemistry
- Publisher
- Informa UK Limited
- Published
- 2009-12
- Volume
- 1
- Issue
- 9
- Pages
- 1643-1670
- ISSN
- 1756-8919 (ISSN-L)
- 1756-8927
- PMC
- PMC3821171
- OpenAlex
- W1989031118
- Cited by
- 242
- References
- 250
- Citations by year
- 2026: 13 · 2025: 15 · 2024: 25 · 2023: 22 · 2022: 28 · 2021: 25 · 2020: 24 · 2019: 13 · 2018: 14 · 2017: 22 · 2016: 16 · 2015: 6 · 2014: 8 · 2013: 2 · 2012: 5
- FWCI
- 0.42
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Future Medicinal Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (R01DK71892)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Heavy Metal Exposure and Toxicity
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Keywords
- iron chelators, iron overload, deferoxamine, deferasirox, deferiprone, oxidative stress, reactive oxygen species, cancer therapy, neurodegenerative diseases, chronic inflammatory diseases, cardiovascular disease, atherosclerosis, plant polyphenols, phytochemicals
- MeSH terms
- Humans, Iron Chelating Agents, Siderophores, Oxidative Stress, Iron Overload
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