| Autor: |
S, Wnendt, M, Finkam, W, Winter, J, Ossig, G, Raabe, K, Zwingenberger |
| Rok vydání: |
1996 |
| Předmět: |
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| Zdroj: |
Chirality. 8(5) |
| ISSN: |
0899-0042 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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