TY - JOUR
T1 - Synthesis of 7-oxasphingosine and -ceramide analogues and their evaluation in a model for apoptosis
AU - Rajan, Roshini
AU - Wallimann, Kurt
AU - Vasella, Andrea
AU - Pace, Deborah
AU - Genazzani, Armando A.
AU - Canonico, Pier Luigi
AU - Condorelli, Fabrizio
PY - 2004/11
Y1 - 2004/11
N2 - 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 murinepromyelocyte-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,Ndimethylsphingosine, 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 IC50 value of 3 n compared to 100 n 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.
AB - 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 murinepromyelocyte-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,Ndimethylsphingosine, 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 IC50 value of 3 n compared to 100 n 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.
UR - http://www.scopus.com/inward/record.url?scp=33645990494&partnerID=8YFLogxK
U2 - 10.1002/cbdv.200490134
DO - 10.1002/cbdv.200490134
M3 - Article
SN - 1612-1872
VL - 1
SP - 1785
EP - 1799
JO - Chemistry and Biodiversity
JF - Chemistry and Biodiversity
IS - 11
ER -