Cytosporones, coumarins, and an alkaloid from the endophytic fungus Pestalotiopsis sp. isolated from the Chinese mangrove plant Rhizophoramucronata.

Chemical examination of the endophytic fungus Pestalotiopsis sp., isolated from the leaves of the Chinese mangrove Rhizophora mucronata, yielded 11 new compounds including cytosporones J-N (1-3, 5-6), five new coumarins pestalasins A-E (8-12), and a new alkaloid named pestalotiopsoid A (14), along with the known compounds cytosporone C (4), dothiorelone B (7), and 3-hydroxymethyl-6,8-dimethoxycoumarin (13). The structures of the new compounds were unambiguously elucidated on the basis of extensive spectroscopic data analysis.

Enniatins A1, B and B1 from an endophytic strain of Fusarium tricinctum induce apoptotic cell death in H4IIE hepatoma cells accompanied by inhibition of ERK phosphorylation.

Enniatins are mycotoxins which have important impact on human health, e.g. as contaminants of cereals, but also are discussed as possible anticancer agents.

Methods for isolation, purification and structural elucidation of bioactive secondary metabolites from marine invertebrates.

In the past few decades, marine natural products bioprospecting has yielded a considerable number of drug candidates. Two marine natural products have recently been admitted as new drugs: Prialt (also known as ziconotide) as a potent analgesic for severe chronic pain and Yondelis (known also as trabectedin or E-743) as antitumor agent for the treatment of advanced soft tissue sarcoma. In this protocol, methods for bioactivity-guided isolation, purification and identification of secondary metabolites from marine invertebrates such as sponges, tunicates, soft corals and crinoids are discussed.

Putrescine bisamides from Aglaia gigantea.

Phytochemical analysis of the leaves of Aglaia gigantea collected in Vietnam yielded three cinnamoyl putrescine bisamide derivatives, which included the known compound dasyclamide ( 1), as well as two new natural products, gigantamide A ( 2) and grandiamide D ( 3). In this study, the structure of dasyclamide ( 1) was confirmed by X-ray crystallography. The structures of the two new alkaloids, gigantamide A ( 2) and grandiamide D ( 3), were elucidated through extensive 1D and 2D NMR spectroscopy and analysis of their mass spectrometric (ESIMS, HRQTOFMS) data.

Antifouling activity of bromotyrosine-derived sponge metabolites and synthetic analogues.

Eighteen brominated sponge-derived metabolites and synthetic analogues were analyzed for antilarval settlement of Balanus improvisus. Only compounds exhibiting oxime substituents including bastadin-3 (4), -4 (1), -9 (2), and -16 (3), hemibastadin-1 (6), aplysamine-2 (5), and psammaplin A (10) turned out to inhibit larval settling at 1 to 10 microM. Analogues of hemibastadin-1 (6) were synthesized and tested for structure activity studies.

Biologically active natural products from Mongolian medicinal plants Scorzonera divaricata and Scorzonera pseudodivaricata.

Chromatographic separation of a crude extract obtained from the aerial parts of the Mongolian medicinal plant Scorzonera divaricata yielded the two new quinic acid derivatives feruloylpodospermic acids A and B. Both compounds feature a feruloyl group and two dihydrocaffeoyl substituents. For feruloylpodospermic acid A, the dihydrocaffeic acid substituents were found esterified at positions 1 and 5 of the quinic acid moiety, while the feruloyl group was attached at position 3.

Kahalalide derivatives from the Indian sacoglossan mollusk Elysia grandifolia.

Two new cyclic depsipeptide derivatives, kahalalides R (1) and S (2), together with two known congeners, kahalalides F (3) and D (4), were isolated from the Indian sacoglossan mollusk Elysia grandifolia. The structures of the new compounds were unambiguously established on the basis of NMR spectroscopic (1H, 13C, COSY, HMBC) and mass spectrometric (FABMS, ESIMS, MALDI-TOF/PSD) data, which also included Marfey amino acid analyses. The new derivative kahalalide R was found to exert comparable or even higher cytotoxicity than the potential drug candidate kahalalide F toward the MCF7 human mammary carcinoma cell line.

Cytotoxic isomalabaricane triterpenes from the marine sponge Rhabdastrella globostellata.

Fourteen isomalabaricane triterpenes were isolated from the marine sponge Rhabdastrella globostellata. In addition to the known compounds globostellatic acids A (1) and D (4) and stelliferin riboside (13), 11 of the compounds were new natural products, which included globostelletin (3), eight new globostellatic acid congeners, F to M (2, 5-11), and two new stelliferin ribosides (12 and 14). The isolated compounds were tested against three different cancer cell lines, L5178Y (mouse lymphoma), HeLa (human cervix carcinoma), and PC-12 (rat pheochromocytoma).

Norlanostane triterpenoidal saponins from the marine sponge melophlussarassinorum.

Along with five known 30-norlanostane-type saponins, sarasinosides A(1) (5A), A3 (6A), I1 (7), I2 (8), and H2 (9), four new triterpenoidal saponin congeners, sarasinosides J (1), K (2), L (3), and M (4), were isolated from the Indonesian sponge Melophlus sarassinorum. Sarasinosides J (1) and K (2) are the 24,25-hydrogenated congeners of the previously described sarasinosides A1 and H2, respectively. The carbon skeleton of sarasinoside M (4) possesses a rearranged 8alpha,9alpha-epoxy-8,9-seconorlanosta-8(14),9(11),24-triene system, which is novel and unprecedented in nature.

Polyphenols from plants used in traditional Indonesian medicine (Jamu): uptake and antioxidative effects in rat H4IIE hepatoma cells.

Phytochemical investigation of plants used in traditional Indonesian medicine (Jamu) yielded lignans (pinoresinol, 9 alpha-hydroxypinoresinol and salicifoliol), flavonoids (3-O-beta-(D)-glucopyranosyl-(1-->6)-beta-(D)-glucopyranosylkaempferol, luteolin and apigenin) and coumarins (coumarin, 8-hydroxycoumarin and 5-hydroxycoumarin). The beneficial effects of the respective plants for human health are thought to be associated with antioxidative activity. In the present study, the antioxidative capacity of the isolated compounds was determined in an in-vitro assay.

New beta-carboline alkaloids from the Andaman Sea sponge Dragmacidon sp.

Chemical investigation of the hithertho undescribed sponge Dragmacidon sp. from the Andaman Sea afforded two new beta-carboline alkaloids, which were named dragmacidonamines A (1) and B (2). The structures of the new compounds were unambiguously established on the basis of NMR spectroscopic (1H, 13C, COSY, 1H detected direct, and long-range 13C-1H correlations) and mass spectrometric (EI and ESIMS) data.

New luffariellolide derivatives from the Indonesian sponge Acanthodendrilla sp.

Investigation of the Indonesian sponge Acanthodendrilla sp. afforded five new luffariellolide-related sesterterpenes, acantholides A-E (1-5), in addition to luffariellolide and its 25-O-methyl and 25-O-ethyl derivatives. All structures were unambiguously established by 1D and 2D NMR and MS spectroscopy.

New imidazole alkaloids from the Indonesian sponge Leucetta chagosensis.

Chemical investigation of the sponge Leucetta chagosensis collected in Indonesia afforded five new imidazole alkaloids, naamine F (2), naamine G (3), kealiinine A (6), kealiinine B (7), and kealiinine C (8), in addition to the known compound naamine A (1). Naamine G (3) exhibited strong antifungal activity against the phytopathogenic fungus Cladosporium herbarum and also showed mild cytotoxicity against mouse lymphoma (L5178Y) and human cervix carcinoma (HeLa) cell lines. In the brine shrimp assay, kealiinine A (6) was more active than naamine G (3).

Aglacins I-K, three highly methoxylated lignans from Aglaia cordata.

Further chemical investigation of the stem bark of Aglaia cordata has led to the isolation and identification of three new lignans, namely, aglacins I-K (1-3), all of which contain two contiguous trimethoxylated phenyl systems. Among them, aglacins I and J (1 and 2) are new members of the aryltetralin cyclic lactol class, while aglacin K (3) is a new example of tetrahydrofuran lignan. The structures of these compounds were established on the basis of spectroscopic data interpretation.

New communesin derivatives from the fungus Penicillium sp. derived from the Mediterranean sponge Axinella verrucosa.

The ethyl acetate extract of Penicillium sp., derived from the Mediterranean sponge Axinella verrucosa, yielded the known compound communesin B (1) and its new congeners communesins C (2) and D (3), as well as the known compounds griseofulvin, dechlorogriseofulvin, and oxaline. All structures were unambiguously established by 1D and 2D NMR and MS data.

New 9-thiocyanatopupukeanane sesquiterpenes from the nudibranch Phyllidia varicosa and its sponge-prey Axinyssa aculeata.

Two new 9-thiocyanatopupukeanane sesquiterpene isomers were isolated as major metabolites from the MeOH extract of the sponge Axinyssa aculeata and from its nudibranch predator Phyllidia varicosa. The presence of the sesquiterpenes was monitored by GC-MS, and the structures were confirmed by both 1D and 2D NMR spectroscopy. The isolated sesquiterpenes were found to be toxic toward brine shrimp at LC(50) of 5 ppm.

Uniquely modified imidazole alkaloids from a calcareous Leucetta sponge.

A Fijian collection of the calcareous sponge Leucetta sp. was investigated and yielded four new imidazole alkaloids. One compound, (+)-calcaridine A (6), is unique in its overall structure and consists of a geminally substituted 2-aminoimidazolidinone.

Eudistomins W and X, two new beta-carbolines from the micronesian tunicate Eudistoma sp.

Chemical investigation of the Micronesian ascidian Eudistoma sp. afforded two new eudistomin congeners, which were designated eudistomins W (1) and X (2). The structures of the new compounds were unambiguously established on the basis of NMR spectroscopic ((1)H, (13)C, COSY, (1)H detected direct, and long-range (13)C-(1)H correlations) and mass spectrometric (EI and ESIMS) data.

Online analysis of xestodecalactones A-C, novel bioactive metabolites from the fungus Penicillium cf. montanense and their subsequent isolation from the sponge Xestospongia exigua.

Fungal isolates of Penicillium cf. montanense were obtained from the marine sponge Xestospongia exiguacollected from the Bali Sea, Indonesia. Culture filtrates of the fungi yielded three novel decalactone metabolites, xestodecalactones A, B, and C (1, 2a, and 2b), consisting of 10-membered macrolides with a fused 1,3-dihydroxybenzene ring.

Swinhoeiamide A, a new highly active calyculin derivative from the marine sponge Theonella swinhoei.

Analysis of the Papua New Guinean sponge Theonella swinhoei afforded a new calyculinamide-related congener for which we propose the name swinhoeiamide A (1). The structure of the new compound was unambiguously established on the basis of NMR spectroscopic ((1)H, (13)C, COSY, HMBC) and mass spectrometric (FABMS) data. Swinhoeiamide A exhibited insecticidal activity toward neonate larvae of the polyphagous pest insect Spodoptera littoralis when incorporated in an artificial diet offered to the larvae in a chronic feeding bioassay (ED(50) 2.

New metabolites from sponge-derived fungi Curvularia lunata and Cladosporium herbarum.

The fungus Curvularia lunata, isolated from the marine sponge Niphates olemda, yielded the new 1,3,8-trihydroxy-6-methoxyanthraquinone, which we named lunatin (1), the known modified bisanthraquinone cytoskyrin A (2), and the known plant hormone (+)-abscisic acid (3). Both anthraquinones were found to be active against Bacillus subtilis, Staphylococcus aureus, and Escherichia coli. Two strains of the fungus Cladosporium herbarum, isolated from the sponges Aplysina aerophoba and Callyspongia aerizusa, respectively, yielded two new alpha-pyrones, herbarin A (4) and herbarin B (5), the known compound citreoviridin A (6), and the new phthalide herbaric acid (7).