Linckosides M–Q: neuritogenic steroid glycosides from the Okinawan starfish Linckia laevigata

Abstract

Five new steroid glycosides, linckosides M–Q (1–5), and two known related metabolites, mimics and/or enhancers of the neuritogenic activity of nerve growth factor (NGF), have been isolated from the Okinawan blue starfish Linckia laevigata. Their structures, including stereochemistry, were elucidated by spectroscopic methods and chemical derivatization. The most active metabolite linckoside P (4) induced neurite outgrowth in 55% of PC12 cells 6 days after treatment. Linckosides M–O (1–3) were less active, in the range 21 to 32%. The monoglycosides, linckoside Q (5) and the two known metabolites, 6 and 7, were much less active than the bisglycosides. All the metabolites enhanced the neuritogenic activity of a trace amount of NGF, from 11% to 60–99% three days after treatment. These structure–activity relationships suggest the importance of xylose on a side chain, especially at the C-24 carbon branch rather than at the terminal C-26, for NGF-mimic activity.