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

Authors:Grijalvo, Santiago
Bedia Girbés, Carmen
Triola Guillem, Gemma
Casas Brugulat, Josefina
Llebaria Soldevilla, Amadeu
Teixidó, Jordi
Rabal, Obdulia
Levade, Thierry
Delgado Cirilo, Antonio
Fabriàs, Gemma
Keywords:Sphingolipids, Ceramide, Farber disease, Ceramidase, Inhibitor
Issue Date:7-Aug-2006
Publisher:Elsevier
Citation:Chemistry and Physics of Lipids 144(1): 69-84 (2006)
Abstract: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.
Description:16 pages, 3 figures, 2 schemes.-- PMID: 16942762 [PubMed].-- Printed version published Oct 2006.
Publisher version (URL):http://dx.doi.org/10.1016/j.chemphyslip.2006.07.001
URI:http://hdl.handle.net/10261/12455
ISSN:0009-3084
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Appears in Collections:(IQAC) Artículos

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