RGD Reference Report - Design, synthesis and activity as acid ceramidase inhibitors of 2-oxooctanoyl and N-oleoylethanolamine analogues. - Rat Genome Database

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Design, synthesis and activity as acid ceramidase inhibitors of 2-oxooctanoyl and N-oleoylethanolamine analogues.

Authors: Grijalvo, S  Bedia, C  Triola, G  Casas, J  Llebaria, A  Teixido, J  Rabal, O  Levade, T  Delgado, A  Fabrias, G 
Citation: Grijalvo S, etal., Chem Phys Lipids. 2006 Oct;144(1):69-84. Epub 2006 Aug 7.
RGD ID: 1599260
Pubmed: PMID:16942762   (View Abstract at PubMed)
DOI: DOI:10.1016/j.chemphyslip.2006.07.001   (Journal Full-text)

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.



Objects referenced in this article
Gene Asah1 N-acylsphingosine amidohydrolase 1 Rattus norvegicus
Gene Asah2 N-acylsphingosine amidohydrolase 2 Rattus norvegicus

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