Skip to content
2000
Volume 32, Issue 21
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

Abstract

Iron, as an essential element, plays a crucial role in ensuring the proper functioning of all living organisms. While the appropriate level of iron for the optimal functioning of organisms cannot be disregarded, an excessive amount of this element can be detrimental and give rise to various issues. Nonetheless, the condition of iron accumulation is exceedingly uncommon in the majority of individuals due to the presence of biological autoregulation systems. However, in certain genetic disorders, such as β-thalassemia major, sickle cell anemia, and others, the nature of the diseases or treatment procedures can lead to an overload of iron. Furthermore, numerous studies have substantiated the role of iron in exacerbating conditions in some non-iron-dependent disorders, such as cardiovascular diseases, cancer, malaria, and microbial infections. For the past few decades, iron-chelating agents have been employed to enhance the quality of life for patients with iron accumulation conditions. This review attempts to express the importance of natural and artificial iron chelating agents, as well as the necessity of their extraction, production, and use in vital situations. It also provides a brief overview of the paths pursued by researchers in these fields to introduce suitable compounds as practical iron scavengers for entry into the pharmaceutical market.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cmc/10.2174/0109298673264118231228042816
2024-01-31
2025-10-09

  • From This Site

    /content/journals/cmc/10.2174/0109298673264118231228042816
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. SabetR. FassihiA. HemmateenejadB. SaghaeiL. MiriR. GholamiM. Computer-aided design of novel antibacterial 3-hydroxypyridine-4-ones: Application of QSAR methods based on the MOLMAP approach.J. Comput. Aided Mol. Des.201226334936110.1007/s10822‑012‑9561‑2 22456859
     [Google Scholar]
  2. HalliwellB. Lipid peroxidation: A radical chain reaction. Free radicals in biology and medicine.Clarendon Press1989188267
     [Google Scholar]
  3. MeiwesJ. FiedlerH.P. HaagH. ZähnerH. Konetschny-RappS. JungG. Isolation and characterization of staphyloferrin A, a compound with siderophore activity from Staphylococcus hyicus DSM 20459.FEMS Microbiol. Lett.1990671-220120610.1111/j.1574‑6968.1990.tb13863.x 2139423
     [Google Scholar]
  4. LiJ. WangS. DuanJ. LeP. LiC. DingY. WangR. GaoY. The protective mechanism of resveratrol against hepatic injury induced by iron overload in mice.Toxicol. Appl. Pharmacol.202142411559610.1016/j.taap.2021.115596 34044072
     [Google Scholar]
  5. UtkurovichN.A. An overview of iron metabolism in health and disease.J. Adv. Med. Med. Res.2021338707810.9734/jammr/2021/v33i830888
     [Google Scholar]
  6. HershkoC. KonijnA.M. LinkG. Iron chelators for thalassaemia.Br. J. Haematol.1998101339940610.1046/j.1365‑2141.1998.00726.x 9633877
     [Google Scholar]
  7. Anne-CathrineS.V. TasneemA. MonaM. MoniqueV. VaniaM. MartinF.B. On iron metabolism and its regulation.Int. J. Mol. Sci.20212294591
     [Google Scholar]
  8. JacobsA. An intracellular transit iron pool.Ciba Found. Symp.19771519110610.1002/9780470720325.ch5
     [Google Scholar]
  9. PipernoA. PelucchiS. MarianiR. Inherited iron overload disorders.Transl. Gastroenterol. Hepatol.202052510.21037/tgh.2019.11.15 32258529
     [Google Scholar]
  10. SilvaA.M.N. HiderR.C. Influence of non-enzymatic post-translation modifications on the ability of human serum albumin to bind iron.Biochim. Biophys. Acta. Proteins Proteomics20091794101449145810.1016/j.bbapap.2009.06.003 19505594
     [Google Scholar]
  11. BerdoukasV. CoatesT.D. CabantchikZ.I. Iron and oxidative stress in cardiomyopathy in thalassemia.Free Radic. Biol. Med.201588Pt A3910.1016/j.freeradbiomed.2015.07.01926216855
     [Google Scholar]
  12. FassihiA. AbediD. SaghaieL. SabetR. FazeliH. BostakiG. DeilamiO. SadinpourH. Synthesis, antimicrobial evaluation and QSAR study of some 3-hydroxypyridine-4-one and 3-hydroxypyran-4-one derivatives.Eur. J. Med. Chem.20094452145215710.1016/j.ejmech.2008.10.022 19056147
     [Google Scholar]
  13. El SayedS.M. Abou-TalebA. MahmoudH.S. BaghdadiH. MariaR.A. AhmedN.S. NaboM.M.H. Percutaneous excretion of iron and ferritin (through Al-hijamah) as a novel treatment for iron overload in beta-thalassemia major, hemochromatosis and sideroblastic anemia.Med. Hypotheses201483223824610.1016/j.mehy.2014.04.001 24857772
     [Google Scholar]
  14. NoguchiC.T. SchechterA.N. The intracellular polymerization of sickle hemoglobin and its relevance to sickle cell disease.Blood19815861057106810.1182/blood.V58.6.1057.1057 7030432
     [Google Scholar]
  15. Saghaie DehkordiL. Design of Orally Active Pyridinone Iron (III)-selective LigandsKing's College London. (University of London).1996
     [Google Scholar]
  16. CohenA.R. GlimmE. PorterJ.B. Effect of transfusional iron intake on response to chelation therapy in β-thalassemia major.Blood2008111258358710.1182/blood‑2007‑08‑109306 17951527
     [Google Scholar]
  17. MilmanN.T. Managing genetic hemochromatosis: An overview of dietary measures, which may reduce intestinal iron absorption in persons with iron overload.Gastroenterol. Res.2021142668010.14740/gr1366 34007348
     [Google Scholar]
  18. DiW. CleggJ. The Thalassemia Syndromes.OxfordBlackwell Scientific1981156191
     [Google Scholar]
  19. GabuttiV. Borgna-PignattiC. 9 Clinical manifestations and therapy of transfusional haemosiderosis.Baillieres Clin. Haematol.19947491994010.1016/S0950‑3536(05)80131‑3 7881160
     [Google Scholar]
  20. SaghaieL. LiuD. HiderR.C. Synthesis of polymers containing 3-hydroxypyridin-4-one bidentate ligands for treatment of iron overload.Res. Pharm. Sci.2015104364377 26600863
     [Google Scholar]
  21. SaghaieL. Sadeghi-aliabadiH. TadayonniaN. MirianM. Hydroxypyridinone derivatives: Synthesis and cytotoxic evaluation.J. Rep. Pharm. Sci.20132151510.4103/2322‑1232.222237
     [Google Scholar]
  22. WaseemA. SheikhN. KosalgeS. Natural Iron Chelators as Potential Therapeutic Agents for the Treatment of Iron Overload Diseases. Trace Elements and Their Effects on Human Health and DiseasesIntechOpen20211243
     [Google Scholar]
  23. RibeiroM. SousaC.A. SimõesM. Harnessing microbial iron chelators to develop innovative therapeutic agents.J. Adv. Res.2022398910110.1016/j.jare.2021.10.010 35777919
     [Google Scholar]
  24. ChuljermH. Deferiprone-resveratrol hybrid, an iron-chelating compound, acts as an antimalarial and hepatoprotective agent in Plasmodium berghei infected mice.Bioinorg. Chem. Appl.202220223869337
     [Google Scholar]
  25. ChenW.J. KungG.P. Gnana-PrakasamJ.P. Role of iron in aging related diseases.Antioxidants202211586510.3390/antiox11050865 35624729
     [Google Scholar]
  26. Sadeghi-AliabadiH. ZanjanchiM.A. SaghaieL. BorzoeiM. Evaluation of the cytotoxic effect of hydroxypyridinone derivatives on HCT116 and SW480 colon cancer cell lines.Pharm. Chem. J.201953538839110.1007/s11094‑019‑02010‑2
     [Google Scholar]
  27. ParhizgarA.R. TahghighiA. Introducing new antimalarial analogues of chloroquine and amodiaquine: A narrative review.Iran. J. Med. Sci.2017422115128 28360437
     [Google Scholar]
  28. ThaithongS. BealeG. Malaria parasites.Chulalongkorn University Printing House1992
     [Google Scholar]
  29. YangY.Z. RanzA. LinX-B. ZhangZ.N. MeshnickS.R. PanH-Z. Daphnetin: A novel antimalarial agent with in vitro and in vivo activity.Am. J. Trop. Med. Hyg.1992461152010.4269/ajtmh.1992.46.15 1311154
     [Google Scholar]
  30. GordeukV.R. ThumaP.E. BrittenhamG.M. Iron chelation therapy for malaria.Adv. Exp. Med. Biol.199435637138310.1007/978‑1‑4615‑2554‑7_39
     [Google Scholar]
  31. TangY.Q. YeQ. HuangH. ZhengW.Y. An overview of available antimalarials: Discovery, mode of action and drug resistance.Curr. Mol. Med.202020858359210.2174/1566524020666200207123253 32031068
     [Google Scholar]
  32. BlolandP.B. Drug Resistance in Malaria, World Health Organization.Available from: https://www.cdc.gov/malaria/resources/pdf/drug_resistance/bloland_who2001.pdf 2001
  33. TiwariR. Synthesis and antimalarial activity of amide and ester conjugates of siderophores and ozonides.Biometals2022362315320 35229216
     [Google Scholar]
  34. MohantyS. PatelD.K. PatiS.S. MishraS.K. Adjuvant therapy in cerebral Malaria.Indian J. Med. Res.20061243245260 17085828
     [Google Scholar]
  35. SaberiS. ZarrabiZ. SaghaieL. FassihiA. PestechianN. Synthesis and comparison of anti- Leishmania major activity of antimony and iron complexes of 3-hydroxypyran-4-one and 3-hydroxypyridine-4-one as bi-dentate ligands.J. Rep. Pharm. Sci.20209217710.4103/jrptps.JRPTPS_64_18
     [Google Scholar]
  36. CharleboisE. LiY. WagnerV. PantopoulosK. OlivierM. Genetic iron overload hampers development of cutaneous leishmaniasis in mice.Int. J. Mol. Sci.2023242166910.3390/ijms24021669 36675185
     [Google Scholar]
  37. NegashK.H. NorrisJ.K.S. HodgkinsonJ.T. Siderophore–antibiotic conjugate design: New drugs for bad bugs?Molecules20192418331410.3390/molecules24183314 31514464
     [Google Scholar]
  38. ZhengT. NolanE.M. Enterobactin-mediated delivery of β-lactam antibiotics enhances antibacterial activity against pathogenic Escherichia coli.J. Am. Chem. Soc.2014136279677969110.1021/ja503911p 24927110
     [Google Scholar]
  39. KocienskiP. Synthesis of cefiderocol. Synfacts2019151001868
     [Google Scholar]
  40. ArosioP. EliaL. PoliM. Ferritin, cellular iron storage and regulation.IUBMB Life201769641442210.1002/iub.1621 28349628
     [Google Scholar]
  41. SullivanJ.L. Is stored iron safe?J. Lab. Clin. Med.2004144628028410.1016/j.lab.2004.10.006 15614249
     [Google Scholar]
  42. SullivanJ.L. The iron paradigm of ischemic heart disease.Am. Heart J.198911751177118810.1016/0002‑8703(89)90887‑9 2653014
     [Google Scholar]
  43. SullivanJ.L. Stored iron as a risk factor for ischemic heart disease. Iron and Human Disease.CRC Press201829531210.1201/9781351073899‑12
     [Google Scholar]
  44. BomfordA. IsaacJ. RobertsS. EdwardsA. YoungS. WilliamsR. The effect of desferrioxamine on transferrin receptors, the cell cycle and growth rates of human leukaemic cells.Biochem. J.1986236124324910.1042/bj2360243 3790074
     [Google Scholar]
  45. VoestE.E. VreugdenhilG. MarxJ.J. Iron-chelating agents in non-iron overload conditions.Ann. Intern. Med.1994120649049910.7326/0003‑4819‑120‑6‑199403150‑00008 8311372
     [Google Scholar]
  46. AmanoS. KainoS. ShinodaS. HarimaH. MatsumotoT. FujisawaK. TakamiT. YamamotoN. YamasakiT. SakaidaI. Invasion inhibition in pancreatic cancer using the oral iron chelating agent deferasirox.BMC Cancer202020168110.1186/s12885‑020‑07167‑8 32698792
     [Google Scholar]
  47. WangF. LvH. ZhaoB. ZhouL. WangS. LuoJ. LiuJ. ShangP. Iron and leukemia: New insights for future treatments.J. Exp. Clin. Cancer Res.201938140610.1186/s13046‑019‑1397‑3 31519186
     [Google Scholar]
  48. BellottiD. RemelliM. Deferoxamine B: A natural, excellent and versatile metal chelator.Molecules20212611325510.3390/molecules26113255 34071479
     [Google Scholar]
  49. SoaresE.V. Perspective on the biotechnological production of bacterial siderophores and their use.Appl. Microbiol. Biotechnol.2022106113985400410.1007/s00253‑022‑11995‑y 35672469
     [Google Scholar]
  50. MohammadH.A. AfshinF. FarshidH. LotfollahS. AhmadM.A. Mohammad-BeigH. Synthesis, antioxidant activity, and density functional theory study of some novel 4-[(benzo [d] thiazol-2-ylimino) methyl] phenol derivatives: A comparative approach for the explanation of their radical scavenging activities.Res. Pharm. Sci.202116135
     [Google Scholar]
  51. PetrakK. Essential properties of drug-targeting delivery systems.Drug Discov. Today20051023-241667167310.1016/S1359‑6446(05)03698‑6 16376827
     [Google Scholar]
  52. ChenY. DalwadiG. BensonH. Drug delivery across the blood-brain barrier.Curr. Drug Deliv.20041436137610.2174/1567201043334542 16305398
     [Google Scholar]
  53. FlorenceA. AttwoodD. Surface and Interfacial Properties of Surfactants. Physicochemical Principles of Pharmacy.2nd EdRed Globe Press1988172227
     [Google Scholar]
  54. HollanderD. Importance of “probe” molecular geometry in determining intestinal permeability.Can. J. Gastroenterol.1988235A38A
     [Google Scholar]
  55. HiderR.C. KongX. Iron: Effect of overload and deficiency.Met. Ions Life Sci.20131322929410.1007/978‑94‑007‑7500‑8_8
     [Google Scholar]
  56. SigelA. SigelH. SigelR.K. Interrelations between essential metal ions and human diseases. Metal Ions in Life Sciences, 1st.DordrechtSpringer201310.1007/978‑94‑007‑7500‑8
     [Google Scholar]
  57. HarrisD.C. AisenP. Facilitation of Fe(II) antoxidation by Fe(III) complexing agents.Biochim. Biophys. Acta, Gen. Subj.1973329115615810.1016/0304‑4165(73)90019‑6
     [Google Scholar]
  58. LiuZ.D. HiderR.C. Design of iron chelators with therapeutic application.Coord. Chem. Rev.20022321-215117110.1016/S0010‑8545(02)00050‑4
     [Google Scholar]
  59. NurchiV.M. PivettaT. LachowiczJ.I. CrisponiG. Effect of substituents on complex stability aimed at designing new iron(III) and aluminum(III) chelators.J. Inorg. Biochem.2009103222723610.1016/j.jinorgbio.2008.10.011 19036454
     [Google Scholar]
  60. MukoseraG.T. LiuT. ManaenM. ZhuL. PowerG. SchroederH. BloodA.B. Deferoxamine produces nitric oxide under ferricyanide oxidation, blood incubation, and UV-irradiation.Free Radic. Biol. Med.202016045847010.1016/j.freeradbiomed.2020.08.004 32828952
     [Google Scholar]
  61. LiuZ.D. HiderR.C. Design of clinically useful iron(III)-selective chelators.Med. Res. Rev.2002221266410.1002/med.1027 11746175
     [Google Scholar]
  62. MaY. ZhouT. KongX. HiderR.C. Chelating agents for the treatment of systemic iron overload.Curr. Med. Chem.201219172816282710.2174/092986712800609724 22455586
     [Google Scholar]
  63. JiangX. ZhouT. BaiR. XieY. Hydroxypyridinone-based iron chelators with broad-ranging biological activities.J. Med. Chem.20206323144701450110.1021/acs.jmedchem.0c01480 33023291
     [Google Scholar]
  64. BudhrajaR. DingC. WalterP. WagnerS. ReemtsmaT. Gary SawersR. AdrianL. The impact of species, respiration type, growth phase and genetic inventory on absolute metal content of intact bacterial cells.Metallomics201911592593510.1039/c9mt00009g 30848269
     [Google Scholar]
  65. ChoiJ.S. SeokY.J. ChoY.H. RoeJ.H. Iron-induced respiration promotes antibiotic resistance in actinomycete bacteria.M.Bio2022132e00425e2210.1128/mbio.00425‑22 35357210
     [Google Scholar]
  66. RishiG. HuangG. SubramaniamV.N. Cancer: The role of iron and ferroptosis.Int. J. Biochem. Cell Biol.202114110609410.1016/j.biocel.2021.106094 34628027
     [Google Scholar]
  67. HiderR.C. Siderophore Mediated Absorption of Iron. Siderophores from Microorganisms and Plants. Structure and Bonding.Berlin, HeidelbergSpringer1984258710.1007/BFb0111310
     [Google Scholar]
  68. RaymondK.N. MüllerG. MatzankeB.F. Complexation of iron by siderophores a review of their solution and structural chemistry and biological function.Struct. Chem.198449102
     [Google Scholar]
  69. JewulaP. GrandmouginM. ChoppinM. TivelliA.M.C. AmatiA. RousselinY. KarmazinL. ChambronJ-C. MeyerM. Complexes of Fe(III) and Ga(III) derived from the cyclic 6- and 7-membered hydroxamic acids found in mixed siderophores.Eur. J. Inorg. Chem.20232613e20230003810.1002/ejic.202300038
     [Google Scholar]
  70. HiderR.C. Mohd-NorA.R. SilverJ. MorrisonI.E.G. ReesL.V.C. Model compounds for microbial iron-transport compounds. Part 1. Solution chemistry and Mössbauer study of iron(II) and iron(III) complexes from phenolic and catecholic systems.J. Chem. Soc., Dalton Trans.1981260962210.1039/DT9810000609
     [Google Scholar]
  71. HiderR.C. HallA.D. Clinically useful chelators of tripositive elements.Prog. Med. Chem.1991284117310.1016/S0079‑6468(08)70363‑1 1843549
     [Google Scholar]
  72. BissetW. JacobsH. KoshtiN. StarkP. GopalanA. Synthesis and metal ion complexation properties of a novel polyethyleneimine N-methylhydroxamic acid water soluble polymer.React. Funct. Polym.200355210911910.1016/S1381‑5148(02)00199‑2
     [Google Scholar]
  73. CrumblissA.L. Aqueous solution equilibrium and kinetic studies of iron siderophore and model siderophore complexes. Handbook of Microbial Iron Chelates.Duke2017177234
     [Google Scholar]
  74. MarmionC.J. GriffithD. NolanK.B. Hydroxamic acids− an intriguing family of enzyme inhibitors and biomedical ligands.Eur. J. Inorg. Chem.20042004153003301610.1002/ejic.200400221
     [Google Scholar]
  75. KeberleH. The biochemistry of desferrioxamine and its relation to iron metabolism.Ann. N. Y. Acad. Sci.1964119275876810.1111/j.1749‑6632.1965.tb54077.x 14219455
     [Google Scholar]
  76. SummersJ.B. GunnB.P. MartinJ.G. MazdiyasniH. StewartA.O. YoungP.R. GoetzeA.M. BouskaJ.B. DyerR.D. BrooksD.W. Orally active hydroxamic acid inhibitors of leukotriene biosynthesis.J. Med. Chem.19883113510.1021/jm00396a002 3336029
     [Google Scholar]
  77. GradyR.W. GrazianoJ.H. AkersH.A. CeramiA. The development of new iron-chelating drugs.J. Pharmacol. Exp. Ther.19761962478485 1255491
     [Google Scholar]
  78. TominagaT. ShimomuraS. TanosakiS. KobayashiN. IkedaT. YamamotoT. TamuraT. UmemuraS. Horibuchi-MatsusakiS. HachiyaM. AkashiM. Effects of the chelating agent DTPA on naturally accumulating metals in the body.Toxicol. Lett.202135028329110.1016/j.toxlet.2021.08.001 34371142
     [Google Scholar]
  79. ReddyJ.D. CobbR.R. DunganN.W. MatthewsL.L. AielloK.V. RitterG. EpplerB. KirkJ.F. AbernethyJ.A. TomisakaD.M. TaltonJ.D. Preclinical toxicology, pharmacology, and efficacy of a novel orally administered diethylenetriaminepentaacetic acid (DTPA) formulation.Drug Dev. Res.201273523224210.1002/ddr.21018
     [Google Scholar]
  80. SugiuraY. TanakaH. MinoY. IshidaT. OtaN. InoueM. NomotoK. YoshiokaH. TakemotoT. Structure, properties, and transport mechanism of iron(III) complex of mugineic acid, a possible phytosiderophore.J. Am. Chem. Soc.1981103236979698210.1021/ja00413a043
     [Google Scholar]
  81. von WirénN. KhodrH. HiderR.C. Hydroxylated phytosiderophore species possess an enhanced chelate stability and affinity for iron(III).Plant Physiol.200012431149115810.1104/pp.124.3.1149 11080292
     [Google Scholar]
  82. SpiroT.G. BatesG. SaltmanP. Hydrolytic polymerization of ferric citrate. II. Influence of excess citrate.J. Am. Chem. Soc.196789225559556210.1021/ja00998a009
     [Google Scholar]
  83. ThiekenA. WinkelmannG.Ã. Rhizoferrin: A complexone type siderophore of the mocorales and entomophthorales (Zygomycetes).FEMS Microbiol. Lett.1992941-2374110.1111/j.1574‑6968.1992.tb05285.x 1387861
     [Google Scholar]
  84. PonkaP. BorováJ. NeuwirtJ. FuchsO. Mobilization of iron from reticulocytes.FEBS Lett.197997231732110.1016/0014‑5793(79)80111‑8 761636
     [Google Scholar]
  85. PoňkaP. BorováJ. NeuwirtJ. FuchsO. NečasE. A study of intracellular iron metabolism using pyridoxal isonicotinoyl hydrazone and other synthetic chelating agents.Biochim. Biophys. Acta, Gen. Subj.1979586227829710.1016/0304‑4165(79)90100‑4 476142
     [Google Scholar]
  86. RichardsonD.R. PonkaP. Pyridoxal isonicotinoyl hydrazone and its analogs: Potential orally effective iron-chelating agents for the treatment of iron overload disease.J. Lab. Clin. Med.1998131430631510.1016/S0022‑2143(98)90180‑9 9579383
     [Google Scholar]
  87. NickH. A new, Potent, Orally Active Iron Chelator.The Saratoga Group Florida2000
     [Google Scholar]
  88. RyabukhinY.I. S.N.; Kuzharov, A. Synthesis and investigation of complex compounds of transition metals with Di (ohydroxyphenyl)-1, 2, 4-oxadiazole and its 1, 2, 4 triazole analogs.Sov. J. Coord. Chem.198713493499
     [Google Scholar]
  89. Al-RadadiN.S. ZayedE.M. MohamedG.G. Abd El SalamH.A. Synthesis, spectroscopic characterization, molecular docking, and evaluation of antibacterial potential of transition metal complexes obtained using triazole chelating ligand.J. Chem.2020202011210.1155/2020/1548641
     [Google Scholar]
  90. PorterJ.B. HuehnsE.R. HiderR.C. 2 The development of iron chelating drugs.Baillieres Clin. Haematol.19892225729210.1016/S0950‑3536(89)80018‑6 2660929
     [Google Scholar]
  91. HiderR.C. HoffbrandA.V. The role of deferiprone in iron chelation.N. Engl. J. Med.2018379222140215010.1056/NEJMra1800219 30485781
     [Google Scholar]
  92. ClarkeE.T. MartellA.E. ReibenspiesJ. Crystal structure of the tris 1,2-dimethyl-3-hydroxy-4-pyridinone (DMHP) complex with the Fe(III) ion.Inorg. Chim. Acta1992196217718310.1016/S0020‑1693(00)86121‑6
     [Google Scholar]
  93. CusnirR. ImbertiC. HiderR. BlowerP. MaM. Hydroxypyridinone chelators: From iron scavenging to radiopharmaceuticals for PET imaging with gallium-68.Int. J. Mol. Sci.201718111610.3390/ijms18010116 28075350
     [Google Scholar]
  94. BergeronR.J. A comparison of the iron-clearing properties of 1,2-dimethyl-3-hydroxypyrid-4-one, 1,2-diethyl-3-hydroxypyrid-4-one, and deferoxamine.Blood199279718821890
     [Google Scholar]
  95. ChavesS. MarquesS.M. MatosA.M.F. NunesA. GanoL. TuccinardiT. MartinelliA. SantosM.A. New tris(hydroxypyridinones) as iron and aluminium sequestering agents: Synthesis, complexation and in vivo studies.Chemistry20101634105351054510.1002/chem.201001335 20665585
     [Google Scholar]
  96. DehkordiL.S. LiuZ.D. HiderR.C. Basic 3-hydroxypyridin-4-ones: Potential antimalarial agents.Eur. J. Med. Chem.20084351035104710.1016/j.ejmech.2007.07.011 17869385
     [Google Scholar]
  97. HiderR. LiuZ. Emerging understanding of the advantage of small molecules such as hydroxypyridinones in the treatment of iron overload.Curr. Med. Chem.200310121051106410.2174/0929867033457629 12678676
     [Google Scholar]
  98. DobbinP.S. HiderR.C. HallA.D. TaylorP.D. SarpongP. PorterJ.B. XiaoG. van der HelmD. Synthesis, physicochemical properties, and biological evaluation of N-substituted 2-alkyl-3-hydroxy-4(1H)-pyridinones: Orally active iron chelators with clinical potential.J. Med. Chem.199336172448245810.1021/jm00069a002 8355246
     [Google Scholar]
  99. UmemuraM. KimJ.H. AoyamaH. HoshinoY. FukumuraH. NakakajiR. SatoI. OhtakeM. AkimotoT. NarikawaM. TanakaR. FujitaT. YokoyamaU. TaguriM. OkumuraS. SatoM. EguchiH. IshikawaY. The iron chelating agent, deferoxamine detoxifies Fe(Salen)-induced cytotoxicity.J. Pharmacol. Sci.2017134420321010.1016/j.jphs.2017.07.002 28779994
     [Google Scholar]
  100. VelasquezJ. WrayA.A. Deferoxamine. StatPearls.StatPearls Publishing2022 32491586
     [Google Scholar]
  101. PorterJ.B. AbeysingheR.D. HoyesK.P. BarraC. HuehnsE.R. BrooksP.N. BlackwellM.P. AranetaM. BrittenhamG. SinghS. DobbinP. HiderR.C. Contrasting interspecies efficacy and toxicology of 1,2-diethy 1–3-hydroxypyridin-4-one, CP9 4, relates to differing metabolism of the iron chelating site.Br. J. Haematol.199385115916810.1111/j.1365‑2141.1993.tb08660.x 8251385
     [Google Scholar]
  102. LiuZ.D. KhodrH.H. LiuD.Y. LuS.L. HiderR.C. Synthesis, physicochemical characterization, and biological evaluation of 2-(1′-hydroxyalkyl)-3-hydroxypyridin-4-ones: novel iron chelators with enhanced pFe3+ values.J. Med. Chem.199942234814482310.1021/jm991080o 10579844
     [Google Scholar]
  103. LiuZ.D. PiyamongkolS. LiuD.Y. KhodrH.H. LuS.L. HiderR.C. Synthesis of 2-amido-3-hydroxypyridin-4(1H)-ones: Novel iron chelators with enhanced pFe3+ values.Bioorg. Med. Chem.20019356357310.1016/S0968‑0896(00)00273‑X 11310590
     [Google Scholar]
  104. KohgoY. IkutaK. OhtakeT. TorimotoY. KatoJ. Body iron metabolism and pathophysiology of iron overload.Int. J. Hematol.200888171510.1007/s12185‑008‑0120‑5 18594779
     [Google Scholar]
  105. LiuZ.D. KhodrH.H. LuS.L. HiderR.C. Design, synthesis and evaluation of N-basic substituted 3-hydroxypyridin-4-ones: Orally active iron chelators with lysosomotrophic potential.J. Pharm. Pharmacol.201052326327210.1211/0022357001773940 10757413
     [Google Scholar]
  106. SaghaieL. Sadeghi-AliabadiH. KafiriM. Synthesis and biological evaluation of bidentate 3-hydroxypyridin-4-ones iron chelating agents.Res. Pharm. Sci.201162117122 22224095
     [Google Scholar]
  107. SaghaieL. Sadeghi-AliabadiH. AshaehshoarM. Synthesis, analysis and cytotoxic evaluation of some hydroxypyridinone derivatives on HeLa and K562 cell lines.Res. Pharm. Sci.201383185195 24019828
     [Google Scholar]
  108. Hermes-LimaM. PonkaP. SchulmanH.M. The iron chelator pyridoxal isonicotinoyl hydrazone (PIH) and its analogues prevent damage to 2-deoxyribose mediated by ferric iron plus ascorbate.Biochim. Biophys. Acta, Gen. Subj.200015232-315416010.1016/S0304‑4165(00)00115‑X 11042379
     [Google Scholar]
  109. ŠtěrbaM. PopelováO. ŠimůnekT. MazurováY. PotáčováA. AdamcováM. KaiserováH. PoňkaP. GeršlV. Cardioprotective effects of a novel iron chelator, pyridoxal 2-chlorobenzoyl hydrazone, in the rabbit model of daunorubicin-induced cardiotoxicity.J. Pharmacol. Exp. Ther.200631931336134710.1124/jpet.106.111468 17003229
     [Google Scholar]
  110. SabetR. BehjatiM. VahabpourR. MemarnejadianA. RostamiM. FassihiA. AghasadeghiM.R. SaghaieL. MiriR. Iron chelation afforded cardioprotection against H2O2-induced H9C2 cell injury: Application of novel 3-hydroxy pyridine-4-one derivatives.Int. J. Cardiol.20121621606310.1016/j.ijcard.2011.11.067 22225757
     [Google Scholar]
  111. PierreJ. BaretP. SerratriceG. Hydroxyquinolines as iron chelators.Curr. Med. Chem.200310121077108410.2174/0929867033457584 12678678
     [Google Scholar]
  112. CrisponiG. NurchiV.M. LachowiczJ.I. Iron chelation for iron overload in thalassemia.Met. Ions Life Sci.2019199498610.1515/9783110527872‑003 30855104
     [Google Scholar]
  113. SaghaieL. MohebiM. FayaziN. EsmaeiliS. RostamiM. BagheriF. AliabadiA. AsadiP. Synthesis, characterization, molecular docking, antimalarial, and antiproliferative activities of benzyloxy-4-oxopyridin benzoate derivatives.Res. Pharm. Sci.202217325226410.4103/1735‑5362.343079 35531137
     [Google Scholar]
  114. HiderR.C. KongX. AbbateV. HarlandR. ConlonK. LukerT. Deferitazole, a new orally active iron chelator.Dalton Trans.201544115197520410.1039/C5DT00063G 25687725
     [Google Scholar]
  115. ShyamM. DevA. SinhaB.N. JayaprakashV. Scaffold based search on the desferithiocin archetype.Mini Rev. Med. Chem.201919191564157610.2174/1389557519666190301151151 30827237
     [Google Scholar]
  116. SpingarnN.E. SartorelliA.C. Synthesis and evaluation of the thiosemicarbazone, dithiocarbazonate, and 2′-pyrazinylhydrazone of pyrazinecarboxaldehyde as agents for the treatment of iron overload.J. Med. Chem.197922111314131610.1021/jm00197a007 533878
     [Google Scholar]
  117. BeckerE. RichardsonD.R. Development of novel aroylhydrazone ligands for iron chelation therapy: 2-Pyridylcarboxaldehyde isonicotinoyl hydrazone analogs.J. Lab. Clin. Med.1999134551052110.1016/S0022‑2143(99)90173‑7 10560945
     [Google Scholar]
  118. OpletalováV. KalinowskiD.S. VejsováM. KunešJ. PourM. JampílekJ. BuchtaV. RichardsonD.R. Identification and characterization of thiosemicarbazones with antifungal and antitumor effects: Cellular iron chelation mediating cytotoxic activity.Chem. Res. Toxicol.20082191878188910.1021/tx800182k 18698850
     [Google Scholar]
  119. PotůčkováE. HruškováK. BurešJ. KovaříkováP. ŠpirkováI.A. PravdíkováK. KolbabováL. HergeselováT. HaškováP. JansováH. MacháčekM. JirkovskáA. RichardsonV. LaneD.J.R. KalinowskiD.S. RichardsonD.R. VávrováK. ŠimůnekT. Structure-activity relationships of novel salicylaldehyde isonicotinoyl hydrazone (SIH) analogs: Iron chelation, anti-oxidant and cytotoxic properties.PLoS One2014911e11205910.1371/journal.pone.0112059 25393531
     [Google Scholar]
  120. HruškováK. PotůčkováE. HergeselováT. LiptákováL. HaškováP. MingasP. KovaříkováP. ŠimůnekT. VávrováK. Aroylhydrazone iron chelators: Tuning antioxidant and antiproliferative properties by hydrazide modifications.Eur. J. Med. Chem.20161209711010.1016/j.ejmech.2016.05.015 27187862
     [Google Scholar]
  121. FerraliM. BambagioniS. CeccantiA. DonatiD. GiorgiG. FontaniM. LaschiF. ZanelloP. CasolaroM. PietrangeloA. Design, synthesis, and physicochemical and biological characterization of a new iron chelator of the family of hydroxychromenes.J. Med. Chem.200245265776578510.1021/jm021022u 12477360
     [Google Scholar]
  122. KongX. ZhouT. NeubertH. LiuZ. HiderR.C. 3-Hydroxy-2-(5-hydroxypentyl)-4H-chromen-4-one: A bidentate or tridentate iron(III) ligand?J. Med. Chem.200649103028303110.1021/jm050905t 16686545
     [Google Scholar]
  123. EkeltchikI. GunJ. LevO. ShelkovR. MelmanA. Bis(hydroxyamino)triazines: versatile and high-affinity tridentate hydroxylamine ligands for selective iron(III) chelation.Dalton Trans.2006101285129310.1039/B513719E 16505907
     [Google Scholar]
  124. GunJ. EkeltchikI. LevO. ShelkovR. MelmanA. Bis-(hydroxyamino)triazines: Highly stable hydroxylamine-based ligands for iron(III) cations.Chem. Commun.2005425319532110.1039/b508138f 16244741
     [Google Scholar]
  125. SunD. MelmanG. LeTourneauN.J. HaysA.M. MelmanA. Synthesis and antiproliferating activity of iron chelators of hydroxyamino-1,3,5-triazine family.Bioorg. Med. Chem. Lett.201020245846010.1016/j.bmcl.2009.11.130 20005708
     [Google Scholar]
  126. SaljooghiA.S. FatemiS.J.A. Clinical evaluation of Deferasirox for removal of cadmium ions in rat.Biometals201023470771210.1007/s10534‑010‑9337‑x 20401682
     [Google Scholar]
  127. KielarF. WangQ. BoyleP.D. FranzK.J. A boronate prochelator built on a triazole framework for peroxide-triggered tridentate metal binding.Inorg. Chim. Acta201239329430310.1016/j.ica.2012.06.011 23439614
     [Google Scholar]
  128. ReisiN. EsmaeilN. GharagozlooM. MoayediB. Therapeutic potential of silymarin as a natural iron-chelating agent in β-thalassemia intermedia.Clin. Case Rep.2022101e0529310.1002/ccr3.5293 35106163
     [Google Scholar]
  129. HiderR.C. KongX. Chemistry and biology of siderophores.Nat. Prod. Rep.201027563765710.1039/b906679a 20376388
     [Google Scholar]
  130. LawsonA.A. OwenE.T. MowatA.G. Nature of anaemia in rheumatoid arthritis. VII. Storage of iron in rheumatoid disease.Ann. Rheum. Dis.196726655255910.1136/ard.26.6.552 6066238
     [Google Scholar]
  131. VinuesaV. McConnellM.J. Recent advances in iron chelation and gallium-based therapies for antibiotic resistant bacterial infections.Int. J. Mol. Sci.2021226287610.3390/ijms22062876 33809032
     [Google Scholar]
  132. LauE.H. CernyE.A. WrightB.J. RahmanY.E. Improvement of iron removal from the reticuloendothelial system by liposome encapsulation of N,N′-bis[2-hydroxybenzyl]-ethylenediamine-N,N′-diacetic acid (HBED). Comparison with desferrioxamine.J. Lab. Clin. Med.19831015806816 6403640
     [Google Scholar]
  133. BergeronR.J. WiegandJ. BrittenhamG.M. HBED: A potential alternative to deferoxamine for iron-chelating therapy.Blood19989141446145210.1182/blood.V91.4.1446 9454776
     [Google Scholar]
  134. PittC.G. BaoY. ThompsonJ. WaniM.C. RosenkrantzH. MettervilleJ. Esters and lactones of phenolic amino carboxylic acids. Prodrugs for iron chelation.J. Med. Chem.19862971231123710.1021/jm00157a020 3806573
     [Google Scholar]
  135. KirchevaN. DudevT. Gallium as an antibacterial agent: A DFT/SMD study of the Ga3+/Fe3+ competition for binding bacterial siderophores.Inorg. Chem.20205996242625410.1021/acs.inorgchem.0c00367 32286066
     [Google Scholar]
  136. RodgersS.J. LeeC.W. NgC.Y. RaymondK.N. Ferric ion sequestering agents. 15. Synthesis, solution chemistry, and electrochemistry of a new cationic analog of enterobactin.Inorg. Chem.198726101622162510.1021/ic00257a030
     [Google Scholar]
  137. XuJ. KullgrenB. DurbinP.W. RaymondK.N. Specific sequestering agents for the actinides. 28. Synthesis and initial evaluation of multidentate 4-carbamoyl-3-hydroxyl-1-methyl-2(1H)-pyridinone ligands for in vivo plutonium(IV) chelation.J. Med. Chem.199538142606261410.1021/jm00014a013 7629800
     [Google Scholar]
  138. ZhouT. WinkelmannG. DaiZ.Y. HiderR.C. Design of clinically useful macromolecular iron chelators.J. Pharm. Pharmacol.201163789390310.1111/j.2042‑7158.2011.01291.x 21635254
     [Google Scholar]
  139. MeyerM. TelfordJ.R. CohenS.M. WhiteD.J. XuJ. RaymondK.N. High-yield synthesis of the enterobactin trilactone and evaluation of derivative siderophore analogs.J. Am. Chem. Soc.199711942100931010310.1021/ja970718n
     [Google Scholar]
  140. StreaterM. TaylorP.D. HiderR.C. PorterJ. Novel 3-hydroxy-2(1H)-pyridinones. Synthesis, iron(III)-chelating properties and biological activity.J. Med. Chem.19903361749175510.1021/jm00168a033 2342069
     [Google Scholar]
  141. ZhouT. LiuZ.D. NeubertH. KongX.L. MaY.M. HiderR.C. High affinity iron(III) scavenging by a novel hexadentate 3-hydroxypyridin-4-one-based dendrimer: Synthesis and characterization.Bioorg. Med. Chem. Lett.200515225007501110.1016/j.bmcl.2005.08.008 16153843
     [Google Scholar]
  142. XuB. KongX.L. ZhouT. QiuD.H. ChenY.L. LiuM.S. YangR.H. HiderR.C. Synthesis, iron(III)-binding affinity and in vitro evaluation of 3-hydroxypyridin-4-one hexadentate ligands as potential antimicrobial agents.Bioorg. Med. Chem. Lett.201121216376638010.1016/j.bmcl.2011.08.097 21937227
     [Google Scholar]
  143. ZhuC.F. QiuD.H. KongX.L. HiderR.C. ZhouT. Synthesis and in-vitro antimicrobial evaluation of a high-affinity iron chelator in combination with chloramphenicol.J. Pharm. Pharmacol.201365451252010.1111/jphp.12013 23488779
     [Google Scholar]
  144. ChavesS. CapeloA. AreiasL. MarquesS.M. GanoL. EstevesM.A. SantosM.A. A novel tripodal tris-hydroxypyrimidinone sequestering agent for trivalent hard metal ions: Synthesis, complexation and in vivo studies.Dalton Trans.201342176033604510.1039/C2DT32361C 23223558
     [Google Scholar]
  145. ZhouT. KongX.L. HiderR.C. Synthesis and iron chelating properties of hydroxypyridinone and hydroxypyranone hexadentate ligands.Dalton Trans.201948103459346610.1039/C8DT05014G 30793715
     [Google Scholar]
  146. ZhouT. KongX.L. LiuZ.D. LiuD.Y. HiderR.C. Synthesis and iron(III)-chelating properties of novel 3-hydroxypyridin-4-one hexadentate ligand-containing copolymers.Biomacromolecules2008951372138010.1021/bm701122u 18373358
     [Google Scholar]
  147. Rodriguez-LucenaD. GaboriauF. RivaultF. SchalkI.J. LescoatG. MislinG.L.A. Synthesis and biological properties of iron chelators based on a bis-2-(2-hydroxy-phenyl)-thiazole-4-carboxamide or -thiocarboxamide (BHPTC) scaffold.Bioorg. Med. Chem.201018268969510.1016/j.bmc.2009.11.057 20036563
     [Google Scholar]
/content/journals/cmc/10.2174/0109298673264118231228042816
Loading
Salvage Structures, Known as Iron Chelating Agents, Acquired from the Nature and Matured in the Labs
Curr. Med. Chem. 32, 4225 (2025); https://doi.org/10.2174/0109298673264118231228042816
/content/journals/cmc/10.2174/0109298673264118231228042816
/content/journals/cmc/10.2174/0109298673264118231228042816
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): cardiovascular; cytotoxicity; HPOs; hydroxypridinone; Iron chelating agents; iron overload; iron scavenger; malaria; microbial infection; siderophore

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test