Hydroxyquinolines as Iron Chelators

Pierre, Jean‐Louis; Baret, Paul; Serratrice, Guy

doi:10.2174/0929867033457584

Cited by 66 publications

(40 citation statements)

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“…More recently, other chelating bidentate units such as 8-hydroxyquinolines (Baret et al 1995;Pierre et al 2003) or hydroxypiridinones (Raymond & Xu 1994) have been used. Except for isonicotinoylhydrazones (which exhibit a higher denticity), the bidentate subunits mentioned above involve a five-membered chelating ring size, whose role will be discussed in the physicochemical part of this paper.…”

Section: The Nature Of the Chelating Subunitsmentioning

confidence: 99%

Design of Iron chelators: Syntheses and iron (III) complexing abilities of tripodal tris-bidentate ligands

et al. 2006

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The interest in synthetic siderophore mimics includes therapeutic applications (iron chelation therapy), the design of more effective agents to deliver Fe to plants and the development of new chemical tools in order to study iron metabolism and iron assimilation processes in living systems. The design of ligands needs a rational approach for the understanding of the metal ion complexing abilities. The octahedral arrangement of donor atoms is the most favourable geometry, allowing the maximum possible distance between their formal or partial negative charges. Hexadentate chelators, usually of the tris-bidentate type, can accommodate the metal coordination sphere and are well-suited to obtain high pFe values. The first part of this review is dedicated to selected synthetic routes, taking into account (i) the nature of the chelating subunits, connecting groups and spacers, (ii) the water-solubility and hydrophilic/lipophilic balance, (iii) the chirality and (iv) the possibility of grafting probes or vectors. In the second part, we discuss the role of the molecular design on complexing abilities (thermodynamics and kinetics). The bidentate 8-hydroxyquinoline moiety offers an alternative to the usual coordinating hydroxamic acids, catechols and/or alpha-hydroxycarboxylic acids groups encountered in natural siderophores. The promizing results obtained with the tris-hydroxyquinoline-based ligand O-TRENSOX are summarized. O-TRENSOX exhibits a high and selective affinity for Fe(III) complexation. Its efficiency in delivering Fe to plants, iron mobilization, cell protection, and antiproliferative effects has been evidenced. Other chelators derived from O-TRENSOX (mixed catechol/8-hydroxyquinoline ligands, lipophilic ligands) are also described. Some results question the relevance of partition coefficients to foresee the activity of iron chelators. The development of probes (fluorescent, radioactive, spin labelled) based on the O-TRENSOX backbone is in progress in order to get insights in the complicated iron metabolism processes.

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Section: The Nature Of the Chelating Subunitsmentioning

confidence: 99%

Design of Iron chelators: Syntheses and iron (III) complexing abilities of tripodal tris-bidentate ligands

et al. 2006

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“…Almost of the natural siderophores are hexadentate ligands and contain a hydroxamic acid, catechol and/or α-hydroxycarboxylic acid metalbinding group (Albrecht & Crumbliss 1998). Synthetic iron chelators based on 8-hydroxyquinoline chelating subunits have been described and have revealed promizing properties in iron chelating therapy as well as in iron nutrition (Pierre et al 2003). Siderophores of the pyoverdin family, produced by fluorescent Pseudomonas are characterized by a chromophore derived from 2,3-amino-6, 7-dihydroxyquinoline (Abdallah 1991).…”

Section: Introductionmentioning

confidence: 99%

Synthesis and iron-binding properties of quinolobactin, a siderophore from a pyoverdine-deficient Pseudomonas fluorescens

2004

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Quinolobactin is a new siderophore produced by a pyoverdine deficient mutant of Pseudomonas fluorescens. A simple and efficient synthesis of quinolobactin is described, starting from xanthurenic acid. The protonation constants of quinolobactin were determined by potentiometric titrations as pKa2 = 5.50+/-0.07, pKa1 = 10.30+/-0.05. The equilibria of the metal complexes were studied by means of spectrophotometric and potentiometric titrations. The overall stability constants of the quinolobactin-FeIII complexes was found to be log beta111 = 18.60+/-0.10, log beta121 = 32.60+/-0.20, log beta120 = 28.20+/-0.25 resulting in a pFeIII value of 18.2 at pH 7.4. The UV-visible spectral parameters of the [FeL2] are in agreement with a complex containing two ligands coordinated to one Fe3+ cation through the oxygen and nitrogen quinoline atoms.

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“…Bidentate derivatives of 8-hydroxyquinoline have been shown to be very effective against various neurodegenerative diseases [51]. An effective chelator used to treat these neurological disorders is clioquinol (CQ, 5-chloro-7-iodoquinolin-8-ol) a hydroxyquinoline antibiotic containing the 8-hydroxy quinoline motif [55]. The CQ acts via effective high-affinity chelation of iron blocking thus the formation of hydrogen peroxide by amyloid beta [56].…”

Section: Redox Metal Chelation Therapymentioning

confidence: 99%

Redox active metal-induced oxidative stress in biological systems

Jomová

Baroš

Valko

2012

Transition Met Chem

171

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A number of studies performed on biological systems have shown that redox-active metals such as iron and copper as well as other transition metals can undergo redox cycling reactions and produce reactive free radicals termed also reactive oxygen species (ROS) or reactive nitrogen species (RNS). The most representative examples of ROS and RNS are the superoxide anion radical and nitric oxide, respectively, both playing a dual role in biological systems. At low/moderate concentrations of ROS and RNS, they can be involved in many physiological roles such as defense against infectious agents, involvement in a number of cellular signaling pathways and other important biological processes. On the other hand, at high concentrations, ROS and RNS can be important mediators of damage to biomolecules involving DNA, membrane lipids, and proteins. One of the most damaging ROS occurring in biological systems is the hydroxyl radical formed via the decomposition of hydrogen peroxide catalyzed by traces of iron, copper and other metals (the Fenton reaction). The hydroxyl radical is known to react with the DNA molecule, forming 8-OHGuanine adduct, which is a good biomarker of oxidative stress of an organism and a potential biomarker of carcinogenesis. This review discusses the role of iron and copper in uncontrolled formation of ROS leading to various human diseases such as cancer, cardiovascular disease, and neurological disorders (Alzheimer's disease and Parkinson's disease). A discussion is devoted to the various protective antioxidant networks against the deleterious action of free radicals. Metal-chelation therapy, which is a modern pharmacotherapy used to chelate redox-active metals and remove toxic metals from living systems to avoid metal poisoning, is also discussed.

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Hydroxyquinolines as Iron Chelators

Cited by 66 publications

References 0 publications

Design of Iron chelators: Syntheses and iron (III) complexing abilities of tripodal tris-bidentate ligands

Design of Iron chelators: Syntheses and iron (III) complexing abilities of tripodal tris-bidentate ligands

Synthesis and iron-binding properties of quinolobactin, a siderophore from a pyoverdine-deficient Pseudomonas fluorescens

Redox active metal-induced oxidative stress in biological systems

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