Linked Life Data

15755652

Source:http://linkedlifedata.com/resource/pubmed/id/15755652

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2005-3-9
pubmed:databankReference
pubmed:abstractText
Natural and synthetic benzotropolone compounds were assessed in vitro for their ability to inhibit hydroxyestradiol methylation by catechol-O-methyltransferase (COMT). The compounds were also modeled in silico with a homology model of human COMT. Purpurogallin (1), purpurogallin carboxylic acid (2), and theaflavin-3,3'-digallate (6) were the most potent inhibitors of 2-hydroxy and 4-hydroxyestradiol methylation (IC(50) 0.22-0.50microM). Compounds 1 and 6 decreased the V(max) and increased the K(m) of COMT, indicating a mixed-type inhibition. Compounds 1 and 2 bound to COMT by inserting the six-membered ring of the benzotropolone into the active site. Decreased acidity of the hydroxyl groups on this ring or increased bulkiness reduced potency. Compound 6 bound by inserting the galloyl ester into the active site, which allowed the compound to overcome increased bulkiness and resulted in restored potency. Further studies are needed to determine the impact in vivo of COMT inhibition by these compounds.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0968-0896
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
13
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2501-7
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:15755652-Catechol O-Methyltransferase, pubmed-meshheading:15755652-Chromatography, High Pressure Liquid, pubmed-meshheading:15755652-Computer Simulation, pubmed-meshheading:15755652-Enzyme Inhibitors, pubmed-meshheading:15755652-Estradiol, pubmed-meshheading:15755652-Humans, pubmed-meshheading:15755652-Kinetics, pubmed-meshheading:15755652-Liver, pubmed-meshheading:15755652-Methylation, pubmed-meshheading:15755652-Models, Molecular, pubmed-meshheading:15755652-Molecular Conformation, pubmed-meshheading:15755652-Molecular Sequence Data, pubmed-meshheading:15755652-Organometallic Compounds, pubmed-meshheading:15755652-Protein Binding, pubmed-meshheading:15755652-Protein Conformation, pubmed-meshheading:15755652-Structure-Activity Relationship, pubmed-meshheading:15755652-Tropolone
pubmed:year
2005
pubmed:articleTitle
Benzotropolone inhibitors of estradiol methylation: kinetics and in silico modeling studies.
pubmed:affiliation
Department of Chemical Biology Rutgers, Ernest Mario School of Pharmacy, The State University of New Jersey, 164 Frelinghuysen Rd, Piscataway, NJ 08854, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, N.I.H., Extramural