Document Detail


3-Hydroxy-(4H)-benzopyran-4-ones as potential iron chelating agents in vivo.
MedLine Citation:
PMID:  11597487     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Increasing evidence suggests that iron plays an important role in tissue damage both during chronic iron overload diseases (i.e., hemochromatosis) and when, in the absence of actual tissue iron overload, iron is delocalised from specific carriers or intracellular sites (inflammation, neurodegenerative diseases, post-ischaemic reperfusion, etc.). In order to be used for therapeutical purposes in vivo, a reliable iron chelator should be capable of preventing the undesired effects that follow the electrochemical activation of iron (see below). Bearing in mind the molecular structure of some flavonols that are able to chelate iron, we synthesised a new oral iron-chelator, 2-methyl-3-hydroxy-4H-benzopyran-4-one (MCOH). We demonstrate that MCOH chelates iron in a 2:1 ratio showing a stability constant of approximately 10(10). MCOH is able to cross cell membranes (erythrocytes, ascite tumour cells) in both directions. Following intraperitoneal administration to rats, it is quickly taken up by the liver and excreted in the urine within 24h. A similar behaviour has been documented after oral administration. We propose that MCOH may represent the prototype of a new class of iron chelating agents to be developed for iron-removal therapy in vivo with the goal of preventing tissue damage caused by the iron redox cycle.
Authors:
M Ferrali; D Donati; S Bambagioni; M Fontani; G Giorgi; A Pietrangelo
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Bioorganic & medicinal chemistry     Volume:  9     ISSN:  0968-0896     ISO Abbreviation:  Bioorg. Med. Chem.     Publication Date:  2001 Nov 
Date Detail:
Created Date:  2001-10-12     Completed Date:  2002-03-15     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  9413298     Medline TA:  Bioorg Med Chem     Country:  England    
Other Details:
Languages:  eng     Pagination:  3041-7     Citation Subset:  IM    
Affiliation:
Department of Physiopathology and Experimental Medicine, Siena University, via A.Moro, 53100, Siena, Italy. ferrali@unisi.it
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MeSH Terms
Descriptor/Qualifier:
Administration, Oral
Animals
Benzopyrans / chemical synthesis,  metabolism,  pharmacokinetics*
Chromones / chemical synthesis,  metabolism,  pharmacokinetics*
Drug Design
Erythrocytes
Feces / chemistry
Iron Chelating Agents / chemical synthesis*,  metabolism,  pharmacokinetics
Liver / chemistry
Male
Molecular Structure
Rats
Rats, Sprague-Dawley
Tumor Cells, Cultured
Urine / chemistry
Chemical
Reg. No./Substance:
0/Benzopyrans; 0/Chromones; 0/Iron Chelating Agents

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