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 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.
Van Overmeire
I
I
Laboratory for Medicinal Chemistry, University of Gent, Harelbekestraat 72, B-9000 Gent, Belgium.
Boldin
S A
SA
Dumont
F
F
Van Calenbergh
S
S
Slegers
G
G
De Keukeleire
D
D
Futerman
A H
AH
Herdewijn
P
P
D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000502:physiology; D002264:Carboxylic Acids / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002478:Cells, Cultured; D002518:Ceramides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D037341:Fumonisins; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D009183:Mycotoxins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
C120317:2-(hexanoylamino)-5-phenylpent-4-ene-1,3-diol; C120316:2-acetamido-4-dodecene-1,3-diol; D002264:Carboxylic Acids; D002518:Ceramides; D037341:Fumonisins; D009183:Mycotoxins; C056933:fumonisin B1