title: Neurotoxic meroditerpenoids from the tropical marine brown alga Stypopodium flabelliforme.
abstract: Brine shrimp toxicity and TLC analysis guided the isolation of five new and biologically active meroditerpenoids [2beta,3alpha-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 1D and 2D NOE experiments. X-ray crystallography confirmed the relative configuration of 2beta,3alpha-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 (LC50 2-25 microM), and three [2beta,3alpha-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 2beta,3alpha-epitaondiol (1), flabellinol (2), and flabellinone (3) displayed moderate cytotoxicity to the NCI-H460 human lung cancer cell line.
authors.affiliation: College of Pharmacy, Oregon State University, Corvallis, Oregon 97331, USA.
authors.forename: Omar M M
authors.initials: OM
authors.lastname: Sabry
authors.forename: Simeon
authors.initials: S
authors.lastname: Andrews
authors.forename: Kerry L
authors.initials: KL
authors.lastname: McPhail
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Goeger
authors.forename: Alexandre
authors.initials: A
authors.lastname: Yokochi
authors.forename: Keith T
authors.initials: KT
authors.lastname: LePage
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Murray
authors.forename: William H
authors.initials: WH
authors.lastname: Gerwick
mesh_terms: D000818:Animals; D001156:Artemia / Q000187:drug effects; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D009474:Neurons / Q000187:drug effects; D009498:Neurotoxins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D019906:Nuclear Magnetic Resonance, Biomolecular; D010219:Papua New Guinea; D000459:Phaeophyceae / Q000737:chemistry*; D051381:Rats; D026941:Sodium Channel Blockers / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D004224:Diterpenes; D009498:Neurotoxins; D026941:Sodium Channel Blockers