Ceramides: branched alkyl chains in the sphingolipid siblings of diacylglycerol improve biological potency.
The synthesis of a small number of ceramide analogues containing a combination of linear and highly branched alkyl chains on either the d-sphingosine or the N-acyl core of the molecule is reported. Regardless of location, the presence of the branched chain improves potency relative to the positive control, C2 ceramide; however, the most potent compound (4) has the branched side chain as part of the d-sphingosine core. The induction of apoptosis by 4 in terms of Annexin V binding and DiOC(6) labeling was superior to that achieved with C2 ceramide.
Kang
Ji-Hye
JH
Laboratory of Medicinal Chemistry, National Cancer Institute, National Institutes of Health, Bldg 376/104, Frederick, MD 21702, United States.
Garg
Himanshu
H
Sigano
Dina M
DM
Francella
Nicholas
N
Blumenthal
Robert
R
Marquez
Victor E
VE
D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D002518:Ceramides / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D015398:Signal Transduction / Q000187:drug effects; D013107:Sphingolipids / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000737:chemistry
D002518:Ceramides; D013107:Sphingolipids