Neurotoxic meroditerpenoids from the tropical marine brown alga Stypopodium flabelliforme

Omar M.M. Sabry, Simeon Andrews, Kerry L. McPhail, Douglas E. Goeger, Alexandre Yokochi, Keith T. LePage, Thomas F. Murray, William H. Gerwick

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Abstract

Brine shrimp toxicity and TLC analysis guided the isolation of five new and biologically active meroditerpenoids [2β,3α-epitaondiol (1), flabellinol (2), flabellinone (3), stypotriolaldehyde (4), and stypohydroperoxide (5)] along with five known compounds from the marine brown alga Stypopodium flabelliforme collected in Papua New Guinea. The planar structures of compounds 1-5 were determined by extensive spectroscopic analysis (1D and 2D NMR, LRMS, HRMS, IR, and UV), while relative configuration was determined by ID and 2D NOE experiments. X-ray crystallography confirmed the relative configuration of 2β,3α-epitaondiol (1), and the modified Mosher's ester method was used to establish its absolute configuration. All of the new metabolites were moderately toxic to murine neuro-2a cells (LC 50 2-25 μM), and three [2β,3α-epitaondiol (1), flabellinol (2), and flabellinone (3)] possessed potent sodium channel blocking activity. Stypotriolaldehyde (4) had a biphasic effect on the concentration of intracellular Ca2+ in rat cerebellar granule neurons (CGN). The previously known compound, stypoldione (6), also modulated intracellular calcium concentration and was cytotoxic in CGN. Metabolites 2β,3α- epitaondiol (1), flabellinol (2), and flabellinone (3) displayed moderate cytotoxicity to the NCI-H460 human lung cancer cell line.

Original languageEnglish (US)
Pages (from-to)1022-1030
Number of pages9
JournalJournal of Natural Products
Volume68
Issue number7
DOIs
StatePublished - Jul 2005

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

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    Sabry, O. M. M., Andrews, S., McPhail, K. L., Goeger, D. E., Yokochi, A., LePage, K. T., Murray, T. F., & Gerwick, W. H. (2005). Neurotoxic meroditerpenoids from the tropical marine brown alga Stypopodium flabelliforme. Journal of Natural Products, 68(7), 1022-1030. https://doi.org/10.1021/np050051f