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.