Potent Inhibition of Acid Ceramidase by Novel B-13 Analogues
Joint Authors
Arenz, Christoph
Proksch, Denny
Klein, Jan Jasper
Source
Issue
Vol. 2011, Issue 2011 (31 Dec. 2011), pp.1-8, 8 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2010-12-09
Country of Publication
Egypt
No. of Pages
8
Main Subjects
Abstract EN
The lipid-signalling molecule ceramide is known to induce apoptosis in a variety of cell types.
Inhibition of the lysosomal acid ceramidase can increase cellular ceramide levels and thus induce apoptosis.
Indeed, inhibitors of acid ceramidase have been reported to induce cell death and to display potentiating effects to classical radio- or chemo therapy in a number of in vitro and in vivo cancer models.
The most potent in vitro inhibitor of acid ceramidase, B-13, recently revealed to be virtually inactive towards lysosomal acid ceramidase in living cells.
In contrast, a number of weakly basic B-13 analogues have been shown to accumulate in the acidic compartments of living cells and to efficiently inhibit lysosomal acid ceramidase.
However, introduction of weakly basic groups at the ω-position of the fatty acid moiety of B-13 led to a significant reduction of potency towards acid ceramidase from cellular extracts.
Herein, we report a novel B-13-derived scaffold for more effective inhibitors of acid ceramidase.
Furthermore, we provide hints for an introduction of basic functional groups at an alternative site of the B-13 scaffold that do not interfere with acid ceramidase inhibition in vitro.
American Psychological Association (APA)
Proksch, Denny& Klein, Jan Jasper& Arenz, Christoph. 2010. Potent Inhibition of Acid Ceramidase by Novel B-13 Analogues. Journal of Lipids،Vol. 2011, no. 2011, pp.1-8.
https://search.emarefa.net/detail/BIM-512473
Modern Language Association (MLA)
Proksch, Denny…[et al.]. Potent Inhibition of Acid Ceramidase by Novel B-13 Analogues. Journal of Lipids No. 2011 (2011), pp.1-8.
https://search.emarefa.net/detail/BIM-512473
American Medical Association (AMA)
Proksch, Denny& Klein, Jan Jasper& Arenz, Christoph. Potent Inhibition of Acid Ceramidase by Novel B-13 Analogues. Journal of Lipids. 2010. Vol. 2011, no. 2011, pp.1-8.
https://search.emarefa.net/detail/BIM-512473
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-512473