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Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/15792
Title: Analogs of the dihydroceramide desaturase inhibitor GT11 modified at the amide function: synthesis and biological activities
Authors: Bedia Girbés, Carmen; Triola Guillem, Gemma; Casas Brugulat, Josefina; Llebaria Soldevilla, Amadeu; Fabriàs, Gemma
Keywords: Dihydroceramide desaturase
Inhibitor GT11
De novo biosynthesis
Issue Date: 8-Sep-2005
Publisher: Royal Society of Chemistry (Great Britain)
Citation: Organic and Biomolecular Chemistry 3(20): 3707-3712 (2005)
Abstract: Dihydroceramide desaturase is the last enzyme in the biosynthesis of ceramide de novo. The cyclopropene-containing sphingolipid GT11 is a competitive inhibitor of dihydroceramide desaturase. The biological effects of chemical modification of the GT11 amide linkage are reported in this article. Either N-methyl substitution or replacement of the amide -carbonyl methylene by oxygen result in inactive compounds. In contrast, both urea (3) and thiourea (4) analogs of GT11, as well as three -ketoamides (5–7), did inhibit the desaturation of N-octanoylsphinganine to N-octanoylsphingosine, although with significantly lower potency than GT11. Furthermore, the -ketoamides 5–7 inhibit the acidic ceramidase with similar potencies (IC50 52–83 µM). Inhibition of the neutral/alkaline ceramidase by these compounds requires around 20-fold higher concentrations. Structure–activity relationships and the biological interest of these compounds are discussed.
Description: 6 pages, 3 figures, 2 schemes, 1 table.-- PMID: 16211106 [PubMed].-- Printed version published Sep 2005.
Publisher version (URL): http://dx.doi.org/10.1039/b510198k
URI: http://hdl.handle.net/10261/15792
ISSN: 1477-0520 (Print)
1477-0539 (Online)
DOI: 10.1039/b510198k
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