Document Detail


Synthesis of 7-oxasphingosine and -ceramide analogues and their evaluation in a model for apoptosis.
MedLine Citation:
PMID:  17191816     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 IC50 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.
Authors:
Roshini Rajan; Kurt Wallimann; Andrea Vasella; Deborah Pace; Armando A Genazzani; Pier Luigi Canonico; Fabrizio Condorelli
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Chemistry & biodiversity     Volume:  1     ISSN:  1612-1880     ISO Abbreviation:  Chem. Biodivers.     Publication Date:  2004 Nov 
Date Detail:
Created Date:  2006-12-28     Completed Date:  2007-02-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101197449     Medline TA:  Chem Biodivers     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  1785-99     Citation Subset:  IM    
Affiliation:
Laboratorium für Organische Chemie, ETH-Hönggerberg, Wolfgang Pauli-Strasse 10, CH-8093 Zürich.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects*,  physiology
Cell Line, Tumor
Ceramides / chemical synthesis*,  pharmacology
Drug Evaluation, Preclinical / methods
Humans
Mice
Sphingosine / analogs & derivatives*,  chemical synthesis*,  pharmacology
Chemical
Reg. No./Substance:
0/Ceramides; 123-78-4/Sphingosine

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