Linked Life Data

10753479

Source:http://linkedlifedata.com/resource/pubmed/id/10753479

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2001-1-26
pubmed:abstractText
N,N'-Bis(3,4,5-trimethoxybenzyl)ethylenediamine-N,N'-diacetic acid (1) was recently described as a new type of iron chelator for protection against oxidative damage. It has a low affinity for iron, but the corresponding iron complex undergoes a site-specific oxidation by hydrogen peroxide through intramolecular aromatic hydroxylation into a highly stable iron phenolato complex, which does not catalyze hydroxyl radical formation. The purpose of this local activation process is to minimize toxicity compared to strong iron chelators, which may interfere with normal iron metabolism. 1 efficiently protects biological molecules against oxidative damage in vitro but not intact cells because of poor membrane permeability. We show here that, among a series of prodrug esters and lipophilic analogues, membrane-permeant N,N'-bis(3,4,5-trimethoxybenzyl)ethylenediamine-N,N'-diacetic acid diacetoxymethyl ester (7) protects human skin fibroblasts against hydrogen peroxide toxicity with an IC(50) of 3 microM. These results thus demonstrate that, providing sufficient intracellular chelator concentration is reached, 1 efficiently protects cells against the deleterious effects of hydrogen peroxide. This strategy of oxidative activation should help the design of new chelators with better safety margins, which may be useful against oxidative damage under conditions where a prolonged administration is needed.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
6
pubmed:volume
43
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1418-21
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Protection against oxidative damage by iron chelators: effect of lipophilic analogues and prodrugs of N,N'-bis(3,4,5-trimethoxybenzyl)ethylenediamine- N,N'-diacetic acid (OR10141).
pubmed:affiliation
Department of Chemistry, L'OREAL Advanced Research, 1 avenue Eugène Schueller, 93601 Aulnay sous Bois, France. jbgaley@recherche.loreal.com
pubmed:publicationType
Journal Article