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.
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Qi J, Ojika M, Sakagami Y (2002) Linckosides A and B, two new neuritogenic steroid glycosides from the Okinawan starfish Linckia laevigata. Bioorg Med Chem 10:1961–1966
Qi J, Ojika M, Sakagami Y (2004) Linckosides C–E, three new neuritogenic steroid glycosides from the Okinawan starfish Linckia laevigata. Bioorg Med Chem 12:4259–4265
Han C, Qi J, Ojika M (2006) Structure–activity relationships of novel neuritogenic steroid glycosides from the Okinawan starfish Linckia laevigata. Bioorg Med Chem 14:4458–4465
Iorizzi M, De Riccardis F, Minale L, Riccio R (1993) Starfish saponins, 52. Chemical constituents from the starfish Echinaster brasiliensis. J Nat Prod 56:2149–2162
Shinoyama H, Yasui T (1988) β-Xylosidase activity and transxylosyl reaction in the presence of water miscible solvents. Nippon Nogeikagaku Kaishi 62:1339–1343
Zollo F, Fiamore E, Minale L (1985) Starfish saponins. XXIV. Two novel steroidal glycosidesulphates from the starfish Echinaster sepositus. Gazz Chim Ital 115:303–306
D’Auria MV, De Riccardis F, Minale L, Riccio R (1990) Synthesis of 24-methyl-26-hydroxysteroid side-chains: models for stereochemical assignments in polyhydroxylated marine steroids. J Chem Soc Perkin Trans 1:2889–2893
D’Auria MV, Paloma LG, Minale L, Riccio R (1990) Stereochemical assignment at C-24 and C-25 of marine 24-ethyl -26-hydroxy steroids through comparison with synthetic (24S,25S)-, (24S,25R)-, (24R,25R)-, (24R,25S)-models. J Chem Soc Perkin Trans 1:2895–2898
Acknowledgments
This work was financially supported by KAKENHI (B) (16310151) from JSPS and Grand-in-Aid for Scientific Research on Priority Areas (18032038) from MEXT, Japan. We are grateful to Akajima Marine Science Laboratory (Establishment of Tropical Marine Ecological Research, Tokyo) for their help with collection of the starfish.
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Han, C., Qi, J. & Ojika, M. Linckosides M–Q: neuritogenic steroid glycosides from the Okinawan starfish Linckia laevigata . J Nat Med 61, 138–145 (2007). https://doi.org/10.1007/s11418-006-0107-6
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DOI: https://doi.org/10.1007/s11418-006-0107-6