Protection of U937 cells against oxidative injury by a novel series of iron chelators
| Autor: | Herve Plessix, Laurence Le Capitaine, Orazio Cantoni, Giovanni Bracciolli, Jacqueline Dumats, Sylvie Genard, Jean-Baptiste Galey, Patrick Pichaud, Odile Destree, Johann Marché, Liliana Brambilla |
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| Rok vydání: | 1998 |
| Předmět: |
Models
Molecular Free Radicals Oxidative phosphorylation Ascorbic Acid medicine.disease_cause Hydroxylation Iron Chelating Agents Biochemistry Ferric Compounds Ferrous chemistry.chemical_compound Structure-Activity Relationship Drug Stability Physiology (medical) medicine Organic chemistry Humans Chelation Ferrous Compounds Hydrogen peroxide Cell Death Metabolism Hydrogen Peroxide U937 Cells Combinatorial chemistry Oxidative Stress chemistry Spectrophotometry Hydroxyl radical Oxidation-Reduction Oxidative stress |
| Zdroj: | Free radical biologymedicine. 25(8) |
| ISSN: | 0891-5849 |
| Popis: | A new series of iron chelators designed to protect tissues against iron-catalysed oxidative damage is described. These compounds are aminocarboxylate derivatives bearing pendant aromatic groups. They were designed to have a relatively low affinity for both ferrous and ferric iron and to be site-specifically oxidizable by hydrogen peroxide through intramolecular aromatic hydroxylation into species with strong iron binding capacity which do not catalyse hydroxyl radical formation. Thus, at the cellular level, oxidative injury is used to convert weak iron chelators into strong iron chelators in order to promote cell survival. The purpose of this local activation process is to minimise toxicity compared to strong iron chelators which may interfere with normal iron metabolism. Compounds within this series were evaluated in vitro in view of their capacity to undergo intramolecular hydroxylation and to protect cultured cells against oxidative injury. Results show that the intramolecular aromatic hydroxylation capacity is critically dependent upon the amino carboxylate chelating moieties and the substituents of the aromatic rings. Cell protection against oxidative injury is only observed with compounds possessing sufficient lipophilicity. The monohydroxylation product of N , N ′-dibenzylethylenediamine N , N ′-diacetic acid, protects cells against both H 2 O 2 and tBuOOH toxicity with IC 50 ’s of 12 and 60 μM, respectively, in agreement with the oxidative activation concept. These results represent the first step toward the development of a new strategy to safe iron chelation for the prevention of oxidative damage. |
| Databáze: | OpenAIRE |
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