Bioactive new metabolites from the green alga Udotea orientalis growing on the Gorgonian coral Pseudopterogorgia rigida.

As part of our continued search for bioactive secondary metabolites from marine sources using a bioassay-guided fractionation technique (Cytotoxic and anti-trypanosome activities), we have examined the organic extract of Papua New Guinean collection of the green alga Udotea orientalis growing on the Gorgonian coral Pseudopterogorgia rigida. Successive HPLC investigations resulted in isolation of three new compounds, (+) curcuepoxide A, (+) curcuepoxide B and (+)-10α-hydroxycurcudiol. Analysis of different spectroscopic data e.g. UV, IR, LRMS, HRMS, 1D NMR and 2D NMR on the isolated compounds allowed for construction of the planar structures. Stereochemistry assignment at C-7 and C-10 in the new compounds was discussed. Isolated compounds were found to be active in an in vitro assay of antitrypanosome activity. The isolated compounds were found to have variable cytotoxic activity in human lung cancer cell lines.

Cytotoxic halogenated monoterpenes from Plocamium cartilagineum.

As a result of our efforts to identify bioactive agents from marine algae, we have isolated and identified one new halogenated monoterpene 1 [(-)-(5E,7Z)-348-trichloro-7-dichloromethyl-3-methyl-157-octatriene] in addition to three known compounds (2, 3 and 4) from the red alga Plocamium cartilagineum collected by hand from the eastern coast of South Africa. Compound 1 was found to be active as a cytotoxic agent in human lung cancer (NCI-H460) and mouse neuro-2a cell lines (IC50 4 µg/mL). Two of these compounds (3 and 4) were found to have cytotoxic activity in other cell line assays, especially against human leukaemia and human colon cancers (IC50 1.3 µg/mL). None of these metabolites were active as sodium channel blockers or activators. All structures were determined by spectroscopic methods (UV, IR, LRMS, HRMS, 1D NMR and 2D NMR). 1D and 2D NOE experiments were carried out on these compounds to confirm the geometry of the double bonds.

Neurotoxic meroditerpenoids from the tropical marine brown alga Stypopodium flabelliforme.

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.