Effect of aromatic short-chain analogues of ceramide on axonal growth in hippocampal neurons

J Med Chem. 1999 Jul 15;42(14):2697-705. doi: 10.1021/jm990091e.

Abstract

A series of D-erythro- and L-threo-ceramide analogues was synthesized and investigated for their ability to reverse the inhibitory effects of fumonisin B(1) (FB(1)) on axonal growth in hippocampal neurons. The analogues contained either a C(7) side chain or a phenyl group substituted for the C(13) residue present in naturally occurring ceramides, while the N-acyl chain length was reduced from C(16)-C(24) to C(2)-C(8). D-erythro-Ceramide 18a with a C(7) 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 FB(1) on axonal growth, although the mechanism remains unclear.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / drug effects*
  • Axons / physiology
  • Carboxylic Acids / antagonists & inhibitors
  • Carboxylic Acids / pharmacology
  • Cells, Cultured
  • Ceramides / chemical synthesis*
  • Ceramides / chemistry
  • Ceramides / pharmacology
  • Fumonisins*
  • Hippocampus / cytology
  • Hippocampus / drug effects*
  • Hippocampus / ultrastructure
  • Mycotoxins / antagonists & inhibitors
  • Mycotoxins / pharmacology
  • Neurons / drug effects
  • Neurons / physiology
  • Neurons / ultrastructure
  • Rats
  • Rats, Wistar
  • Structure-Activity Relationship

Substances

  • 2-(hexanoylamino)-5-phenylpent-4-ene-1,3-diol
  • 2-acetamido-4-dodecene-1,3-diol
  • Carboxylic Acids
  • Ceramides
  • Fumonisins
  • Mycotoxins
  • fumonisin B1