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Journal of Lipids
Volume 2011, Article ID 971618, 8 pages
Research Article

Potent Inhibition of Acid Ceramidase by Novel B-13 Analogues

Institut für Chemie, Humboldt Universität zu Berlin, Brook-Taylor-Str 2, 12489 Berlin, Germany

Received 28 July 2010; Revised 1 October 2010; Accepted 26 October 2010

Academic Editor: Angel Catala

Copyright © 2011 Denny Proksch et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.