Synthesis of 7-Oxasphingosine and -ceramide Analogues and Their Evaluation in a Model for Apoptosis

✍ Scribed by Roshini Rajan; Kurt Wallimann; Andrea Vasella; Deborah Pace; Armando A. Genazzani; Pier Luigi Canonico; Fabrizio Condorelli

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 333 KB
• Volume: 1
• Category: Article
• ISSN: 1612-1872
• DOI: 10.1002/cbdv.200490134

✦ Synopsis

Abstract

The 7‐oxasphingosine (1), 7‐oxaceramide (2), the thio‐oxaceramide 3, and N‐methyloxaceramide 4 were synthesised from D‐galactose via the building block 9. The apoptosis‐inducing properties of 1–4 were compared to those of sphingosine (Sph) and ceramide (Cer) using a human neuroblastoma (SK‐N‐BE) and a murine‐promyelocyte‐derived (32d) cell line. There were no differences between 2–4 and Cer in terms of their effects on the viability of cells and their ability to trigger cell proliferation. However, in the presence of N,N‐dimethylsphingosine, an inhibitor of sphingosine kinase (SPHK), Cer was more potent than thio‐ceramide 3 in 32d cells, while thio‐ceramide 3 was more potent and efficacious in SK‐N‐BE cells, where it showed an IC~50~ value of 3 nM compared to 100 nM for Cer. In both SK‐N‐BE and 32d cells, 7‐oxasphingosine (1) and Sph were equally toxic, even in the presence of N,N‐dimethylsphingosine.