Effect of Aromatic Short-Chain Analogues of Ceramide on Axonal Growth in Hippocampal Neurons

A series of d-erythro- and l-threo-ceramide analogues was synthesized and investigated for their ability to reverse the inhibitory effects of fumonisin B1 (FB1) on axonal growth in hippocampal neurons. The analogues contained either a C7 side chain or a phenyl group substituted for the C13 residue present in naturally occurring ceramides, while the N-acyl chain length was reduced from C16−C24 to C2−C8. d-erythro-Ceramide 18a with a C7 side chain and an N-acetyl residue and d-erythro-ceramide 20c with an aromatic side chain and an N-hexanoyl residue were most active in reversing the inhibitory effects of FB1 on axonal growth, although the mechanism remains unclear.