| Abstract
| - The biological activity of synthetic ceramide analogues, having modified sphingoid and N-acylchains, as well as fluorine substituents in the allylic position, was investigated in hippocampalneurons. Their influence on axonal growth was compared to that of C6-N-acyl analogues ofnatural ceramides. d-erythro-Ceramides with a phenyl group in the sphingoid moiety and ashort N-acyl chain were able to reverse the inhibitory effect of fumonisin B1 (FB1), but not ofd-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP), on accelerated axonalgrowth in hippocampal neurons. Moreover, we demonstrated that a ceramide analogue withan aromatic ring in the sphingoid moiety is recognized as a substrate by glucosylceramidesynthase, which suggests that the observed biological effects are mediated by activation of theceramide analogue via glucosylation. Introduction of a methyl, pentyl, fluoro, or methoxysubstituent in the para position of the phenyl ring in the sphingoid moiety yielded partly activecompounds. Likewise, substitution of the benzene ring for a thienyl group did not abolish theability to reverse the inhibition of accelerated axonal growth by FB1. Both d-erythro- and l-threo-ceramide analogues, having an allylic fluorine substituent, partly reversed the FB1 inhibition.
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