Source:http://linkedlifedata.com/resource/pubmed/id/15689166
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
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| pubmed:dateCreated |
2005-2-3
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| pubmed:abstractText |
Altering the lipophilicity (log P(app)) of desferrithiocin analogues can change the organ distribution of the chelators and lead to enhanced iron clearance. For example, alkylation of (S)-2-(2,4-dihydroxyphenyl)-4,5-dihydro-4-methyl-4-thiazolecarboxylic acid [(S)-4'-(HO)-DADFT] and its analogues to more lipophilic compounds, such as (S)-4,5-dihydro-2-(2-hydroxy-4-methoxyphenyl)-4-methyl-4-thiazolecarboxylic acid [(S)-4'-(CH3O)-DADFT], provides ligands that achieved between a 3- and 8-fold increase in chelator concentrations in the heart, liver, and pancreas (the organs most at risk in iron-overload disease) of treated rodents. The 4'-O-methylated compounds are demethylated to their hydroxylated counterparts in rodents; furthermore, this O-demethylation takes place in both rodent and human liver microsomes. The relationship between chelator lipophilicity and iron-clearing efficacy in the iron-overloaded Cebus apella primate is further underscored by a comparison of the iron-clearing efficiency of (S)-2-(2,3-dihydroxyphenyl)-4,5-dihydro-4-methyl-4-thiazolecarboxylic acid [(S)-3'-(HO)-DADFT] and its 3'-(CH3O) counterpart. Finally, these DFT analogues are shown to be both inhibitors of the iron-mediated oxidation of ascorbate as well as effective radical scavengers.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antioxidants,
http://linkedlifedata.com/resource/pubmed/chemical/Ascorbic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Catechols,
http://linkedlifedata.com/resource/pubmed/chemical/Dihydropyridines,
http://linkedlifedata.com/resource/pubmed/chemical/Free Radical Scavengers,
http://linkedlifedata.com/resource/pubmed/chemical/Iron,
http://linkedlifedata.com/resource/pubmed/chemical/Iron Chelating Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Thiazoles,
http://linkedlifedata.com/resource/pubmed/chemical/desferrithiocin
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| pubmed:status |
MEDLINE
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| pubmed:month |
Feb
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| pubmed:issn |
0022-2623
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
10
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| pubmed:volume |
48
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
821-31
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:15689166-Animals,
pubmed-meshheading:15689166-Antioxidants,
pubmed-meshheading:15689166-Ascorbic Acid,
pubmed-meshheading:15689166-Catechols,
pubmed-meshheading:15689166-Cebus,
pubmed-meshheading:15689166-Dihydropyridines,
pubmed-meshheading:15689166-Free Radical Scavengers,
pubmed-meshheading:15689166-Humans,
pubmed-meshheading:15689166-Iron,
pubmed-meshheading:15689166-Iron Chelating Agents,
pubmed-meshheading:15689166-Liver,
pubmed-meshheading:15689166-Male,
pubmed-meshheading:15689166-Myocardium,
pubmed-meshheading:15689166-Oxidation-Reduction,
pubmed-meshheading:15689166-Pancreas,
pubmed-meshheading:15689166-Rats,
pubmed-meshheading:15689166-Rats, Sprague-Dawley,
pubmed-meshheading:15689166-Structure-Activity Relationship,
pubmed-meshheading:15689166-Thiazoles,
pubmed-meshheading:15689166-Tissue Distribution
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| pubmed:year |
2005
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| pubmed:articleTitle |
Partition-variant desferrithiocin analogues: organ targeting and increased iron clearance.
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| pubmed:affiliation |
Department of Medicinal Chemistry, University of Florida, Gainesville, Florida 32610-0485, USA. bergeron@mc.cop.ufl.edu
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| pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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