Bioorganic & Medicinal Chemistry 2009-02-15

Ceramides: branched alkyl chains in the sphingolipid siblings of diacylglycerol improve biological potency.

Ji-Hye Kang, Himanshu Garg, Dina M Sigano, Nicholas Francella, Robert Blumenthal, Victor E Marquez

Index: Bioorg. Med. Chem. 17 , 1498-505, (2009)

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Abstract

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.