| Autor: |
Grijalvo S; Research Unit on Bioactive Molecules (RUBAM), Departament de Química Orgànica Biològica, Institut d'Investigacions Químiques i Ambientals de Barcelona (IIQAB-CSIC), Jordi Girona 18-26, E-08034 Barcelona, Spain., Bedia C, Triola G, Casas J, Llebaria A, Teixidó J, Rabal O, Levade T, Delgado A, Fabriàs G |
| Jazyk: |
angličtina |
| Zdroj: |
Chemistry and physics of lipids [Chem Phys Lipids] 2006 Oct; Vol. 144 (1), pp. 69-84. Date of Electronic Publication: 2006 Aug 07. |
| DOI: |
10.1016/j.chemphyslip.2006.07.001 |
| Abstrakt: |
The synthesis of novel N-acylethanolamines and their use as inhibitors of the aCDase is reported here. The compounds are either 2-oxooctanamides or oleamides of sphingosine analogs featuring a 3-hydroxy-4,5-hexadecenyl tail replaced by ether or thioether moieties. It appears that, within the 2-oxooctanamide family, the C3-OH group of the sphingosine molecule is required for inhibition both in vitro and in cultured cells. Furthermore, although the (E)-4 double bond is not essential for inhibitory activity, the (E) configuration is required, since the analogue with a (Z)-4 unsaturation was not inhibitory. None of the oleamides inhibited the aCDase in vitro. Conversely, with the exception of N-oleoylethanolamine and its analogs with S-decyl and S-hexadecyl substituents, all the synthesized oleamides inhibited the aCDase in cultured cells, although with a relatively low potency. We conclude that novel aCDase inhibitors can evolve from N-acylation of sphingoid bases with electron deficient-acyl groups. In contrast, chemical modification of the N-oleoylsphingosine backbone does not seem to offer an appropriate strategy to obtain aCDase inhibitors. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
Full Text from ScienceDirect