Linked Life Data

8900028

Source:http://linkedlifedata.com/resource/pubmed/id/8900028

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1997-1-30
pubmed:abstractText
The question whether the immunomodulating activity of rac-thalidomide resides in either the (-)-(S)- or the (+)-(R)-enantiomer was addressed by synthesis and separation of pure enantiomers of thalidomide analogues which carry a methyl-group at the asymmetric carbon atom and are thus prevented from racemization. The effect of the pure enantiomers of the thalidomide-analogues and also of the enantiomers of thalidomide on release of TNF-alpha was tested in vitro by using stimulated peripheral mononuclear blood cells. Both enantiomers of thalidomide inhibited the release of TNF-alpha equally well at low concentrations (5 and 12.5 micrograms/ml) but at higher concentrations (25 and 50 micrograms 50 micrograms/ml) there was a weak but statistically significant selectivity towards the (-)-(S)-enantiomer. In the case of the configuration-stable thalidomide-analogues there was a very pronounced and statistically significant enantioselectivity towards the (S)-form even at lower concentrations (> or = 5 micrograms/ml). The (S)-enantiomers of the thalidomide-analogues differed in their inhibitory potency from (-)-(S)-thalidomide suggesting that the introduction of the methyl-group increases the TNF-alpha-inhibitory activity while the reduction of one of the carbonyl-functions in the glutarimide-moiety to a methylene-group decreases activity. The effect of these small molecular alterations on activity and the enantioselectivity towards the (S)-enantiomers may indicate that thalidomide and its analogues directly interact with one or several cellular target-proteins.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0899-0042
pubmed:author
pubmed:issnType
Print
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
390-6
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Enantioselective inhibition of TNF-alpha release by thalidomide and thalidomide-analogues.
pubmed:affiliation
Department of Molecular Pharmacology, Gruenenthal Centre of Research, Aachen, Germany.
pubmed:publicationType
Journal Article