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Focused on our interest to develop novel antiparasistic agents, the present study was aimed to evaluate the biological activity of an extract of Laurencia johnstonii collected in Baja California Sur, Mexico, against an Acantamoeba castellanii Neff strain. Bioassay-guided fractionation allowed us to identify the amoebicidal diastereoisomers &alpha, bromocuparane (4) and &alpha, isobromocuparane (5). Furthermore, bromination of the inactive laurinterol (1) and isolaurinterol (2) yielded four halogenated derivatives, (6)&ndash, (9), which improved the activity of the natural sesquiterpenes. Among them, the most active compound was 3&alpha, bromojohnstane (7), a sesquiterpene derivative which possesses a novel carbon skeleton johnstane.

Focused on our interest to develop novel antiparasistic agents, the present study was aimed to evaluate the biological activity of an extract of Laurencia johnstonii collected in Baja California Sur, Mexico, against an Acantamoeba castellanii Neff strain. Bioassay-guided fractionation allowed us to identify the amoebicidal diastereoisomers α-bromocuparane (4) and α-isobromocuparane (5). Furthermore, bromination of the inactive laurinterol (1) and isolaurinterol (2) yielded four halogenated derivatives, (6)–(9), which improved the activity of the natural sesquiterpenes. Among them, the most active compound was 3α-bromojohnstane (7), a sesquiterpene derivative which possesses a novel carbon skeleton johnstane.

Nine new cembranoids 1–9 containing an α–methylene–γ–butyrolactone together with the known diterpenes 10–15 have been isolated from a crude extract of Eunicea sp. and their structures were established by spectroscopic methods. The proliferative effect of six of these compounds on insulin-producing cells (beta–cells) was evaluated., This work was funded by the Ministerio de Ciencia e Innovación (SAF2009-0839 and RTA 2015-00010-C03-02). ARDM acknowledges financial support from Cabildo de Tenerife and Agustin de Betancourt Programme 2016. GP acknowledges a fellowship from Programa JAE-Pre (CSIC).

This article belongs to the Special Issue Progress on Marine Natural Products as Lead Compounds., Two new chloro-furanocembranolides (1, 2) and two new 1,4-diketo cembranolides (3, 4) were isolated from the crude extract of Leptogorgia sp. together with a new seco-furanocembranolide (5) and the known Z-deoxypukalide (6), rubifolide (7), scabrolide D (8) and epoxylophodione (9). Their structures were determined based on spectroscopic evidence. Four compounds: 1, 2, 7 and 8 were found to activate the proliferation of pancreatic insulin-producing (beta) cells., This work was supported by the Ministerio de Ciencia e Innovación (SAF2009-0839 and RTA 2015-00010-C03-02). ARDM acknowledges funding from IMBRAIN project (FP7-REGPOT-2012-CT2012-31637-IMBRAIN) and from Cabildo de Tenerife (Agustín de Betancourt Programme). A.B.G. would like to thank Convenio Universidad de Magallanes (Chile) and CSIC, project 2009CL0031, for financial support.

This work was supported by the Spanish Ministerio de Ciencia e Innovacion (MICINN) (SAF2009‐0839). F. C. acknowledges financial support from the Programa JAE‐Pre (CSIC). A.R. D.‐M. acknowledges funding from the IMBRAIN project (FP7‐REGPOT‐2012‐CT2012‐31637‐IMBRAIN). The Government of Panama granted permission for the collection of the samples. C. C. is supported by a “Waxweiler grant for cancer prevention research” from the Action LIONS Vaincre le Cancer. This work was also supported by Televie Luxembourg, the Recherche Cancer et Sang foundation, and the Recherches Scientifiques Luxembourg association. The authors thank the Een Haerz fir Kriibskrank Kanner association and the Action LIONS Vaincre le Cancer for generous support. Further support was received from the European Union (EU) (ITN “RedCat” 215009 and Interreg IVa project “Corena”). M. D. was supported by the Korean National Research Foundation (NRF), MEST [Tumor Microenvironment Global Core Research Center (GCRC), grant number 2012‐0001184].

This article belongs to the Special Issue Marine Compounds and Inflammation II, 2017., Type 2 diabetes (T2DM) is a complex disease linked to pancreatic beta-cell failure and insulin resistance. Current antidiabetic treatment regimens for T2DM include insulin sensitizers and insulin secretagogues. We have previously demonstrated that leptolide, a member of the furanocembranolides family, promotes pancreatic beta-cell proliferation in mice. Considering the beneficial effects of leptolide in diabetic mice, in this study, we aimed to address the capability of leptolide to improve insulin resistance associated with the pathology of obesity. To this end, we tested the hypothesis that leptolide should protect against fatty acid-induced insulin resistance in hepatocytes. In a time-dependent manner, leptolide (0.1 µM) augmented insulin-stimulated phosphorylation of protein kinase B (PKB) by two-fold above vehicle-treated HepG2 cells. In addition, leptolide (0.1 µM) counteracted palmitate-induced insulin resistance by augmenting by four-fold insulin-stimulated phosphorylation of PKB in HepG2 cells. In vivo, acute intraperitoneal administration of leptolide (0.1 mg/kg and 1 mg/kg) improved glucose tolerance and insulin sensitivity in lean mice. Likewise, prolonged leptolide treatment (0.1 mg/kg) in diet-induced obese mice improved insulin sensitivity. These effects were paralleled with an ~50% increased of insulin-stimulated phosphorylation of PKB in liver and skeletal muscle and reduced circulating pro-inflammatory cytokines in obese mice. We concluded that leptolide significantly improves insulin sensitivity in vitro and in obese mice, suggesting that leptolide may be another potential treatment for T2DM, This research has been funded by Sociedad Española de Diabetes (Ayudas Investigación Básica 2014), Salud Castilla y León (BIO/VA40/15) and Ministerio de Economía y Competitividad-Spain (SAF2014-58702-C2-1-R) to I.C. and Ministerio de Economía y Competitividad-Spain (SAF2014-58702-C2-2-R) to G.P., We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI).

Ptilonines A−F, pyranosylmagellanicus D−E and magellenediol are previously undescribed acetogenins isolated from the red alga Ptilonia magellanica. Their structures were determined from spectroscopic evidence. The absolute configuration of the known pyranosylmagellanicus A, was established by derivatization with (R)− and (S)−α−methoxy −α−phenylacetic acids (MPA). Ptilonines exhibit an unusual halogenation pattern, that may confer evolutionary advantages to Ptilonia magellanica, for which a biogenetic origin is proposed. The antimicrobial effect of some of these compounds was evaluated., This work was supported by the Ministerio de Ciencia e Innovación (SAF2009-0839 and RTA 2015-00010-C03-02). ARDM acknowledges funding from IMBRAIN project (FP7-REGPOT-2012-CT2012-31637-IMBRAIN). A.B.G. would like to thank Convenio Universidad de Magallanes (Chile) and CSIC, project 2009CL0031 and Programa PR-F2-03-CRN16 for financial support.

[EN] The marine actinobacterium AMS370, identified as Salinispora arenicola by 16S rRNA amplified gene comparison, was isolated from sediments of the Gulf of California, Mexico. From its semi-polar extract, 8 known compounds were isolated: 4-Hydroxy-phenyl acetic acid (1), 5-Methyl-2-methylene-2,3-dihydro-1H-pyrimidin-4-one (2), 1H-Pyrimidine-2,4-dione (3), 3-amino-5-hydroxy-benzoic acid (4), 2-(4-Amino-imidazol-[4,5-d]pyridazin-1-yl)-5-hydroxymethyl-4-methyl-tetrahydro-furan-3-ol (5), 3-(4-Hydroxy-phenyl)-acrylic acid methyl ester (6), 3-Benzyl-6-isobutyl-piperazine-2,5-dione (7) and 5,8-epidioxy-(22E,24R)-ergosta-6,22-dien-3-ol (Ergosterol peroxide) (8). The chemical identification was performed by comparison of their NMR spectra against the NMR spectra of the original compounds. This is the first time that compound 4 is reported as a natural product obtained from the Salinispora genus. The crude extract and all the fractions obtained were tested for antibiotic activity against Bacillus cereus, Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae, Proteus mirabilis, Staphylococcus aureus, Salmonella sp. and antifungic activity against Candida albicans. Also, breast cancer (MCF-7), cervical cancer (HeLa) and colorectal cancer cell lines (HCT-116) were tested to determine their cytotoxic activity. Only the semi-polar crude extract and its fractions 5.1 and 5.2 were active against Klebsiella pneumoniae and Staphylococcus aureus., [ES] La actinobacteria marina AMS370, identificada mediante comparación de las secuencias del gen 16S del ARNr como Salinispora arenicola, fue aislada a partir de sedimento del Golfo de California, México. De su extracto semi-polar, se aislaron 8 compuestos conocidos: ácido-4-Hidroxi-fenil acético (1), 5-Metil-2-metilen-2,3-dihidro-1H-pirimidin-4-ona (2), 1H-Pirimidin-2,4-diona (3), ácido-3-amino-5-hidroxi-benzoico (4), 2-(4-Amino-imidazol-[4,5-d]piridazin-1-il)-5-hidroximetil-4-metil-tetrahidro -furan-3-ol (5), Acrilato de 3-(4-Hidroxi-genil)-metilo (6), 3-Bencil-6-isobutil-piperazin-2,5-diona (7) y 5,8-epidioxi-(22E,24R)-ergosta-6,22-dien-3-ol (Peróxido de Ergosterol) (8). La identificación química fue realizada mediante comparación de sus espectros de RMN con los espectros de los compuestos originales. Ésta sería la primera ocasión que el compuesto 4 se reporta como un producto natural a partir del género Salinispora. El extracto crudo y todas sus fracciones fueron ensayadas contra Bacillus cereus, Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae, Proteus mirabilis, Staphylococcus aureus, Salmonella sp. y Candida albicans para probar su actividad antibiótica y antifúngica en el caso de la última especie. Asimismo se evaluó su actividad citotóxica frente a las líneas celulares de cáncer de mama (MCF-7), cervicouterino (HeLa) y colorectal (HCT-116). Solamente el extracto crudo semipolar y las fracciones 5.1 y 5.2 resultaron activas contra Klebsiella pneumoniae y Staphylococcus aureus., We thank the financial support provided by the UABC through the XV Internal Assembly, and the Consejo Nacional de Ciencia y Tecnología (México) 2011 Basic Science Grant No. 168484 and by the Ministerio de Ciencia e Innovación (SAF2009-08039; SAF2010-16858). We also thank the CONACYT for the pre-doctorate fellowship given to FCM (No. 206455) and to AMIM (No. 252250).

The cembranoid 1 and the furanocembranolides 2–4 along with the known pukalide were isolated from Leptogorgia sp. and their structures determined spectroscopically. The 1,4-diketo-cembranoid 1 follows an oxidation pattern of C-18 that reinforces the concept of oxidation profile of C-18 as taxonomical marker for octocorals. The co-occurrence within a species of furanocembranolide/1,4-diketo-cembranoid congeners 1/2–4 raises the question about which one is the biogenetic precursor. A biogenetic pathway is proposed.

Gomerolactones A–D along with the known majusculone, obtusol, and elatol were isolated from Laurencia majuscula, and their structures were determined spectroscopically. With the aid of Pirkle's reagent at low temperature, NMR spectroscopy was used to determine the absolute configuration at the ring closure carbon atom of a α-alkylidene-γ-lactone and an α-alkylidene-δ-lactone unit embedded in the chamigrene network of compounds 1 and 2, respectively. The absolute stereochemistry of compounds 3 and 4 was determined by X-ray analysis. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Two novel sesterterpenes, 1 and 3, containing a scalarane-based framework, have been isolated from the sponge Hyrtios erectus collected in Papua New Guinea. Their structures and relative stereochemistry have been elucidated by analysis of their spectroscopic data.

G(2) checkpoint inhibitors can force cells arrested in G(2) phase by DNA damage to enter mitosis. In this manner, several G(2) checkpoint inhibitors can enhance killing of cancer cells by ionizing radiation and DNA-damaging chemotherapeutic agents, particularly in cells lacking p53 function. All G(2) checkpoint inhibitors identified to date target protein phosphorylation by inhibiting checkpoint kinases or phosphatases. Using a phenotypic cell-based assay for G(2) checkpoint inhibitors, we have screened a large collection of plant extracts and identified Z-Cryptofolione and Cryptomoscatone D2 as highly efficacious inhibitors of the G(2) checkpoint. These compounds and related pyrones also inhibit nuclear export. Leptomycin B, a potent inhibitor of Crm1-mediated nuclear export, is also a very potent G(2) checkpoint inhibitor. These compounds possess a reactive Michael acceptor site and do not appear promising as a radiosensitizing agents because they are toxic to unirradiated cells at checkpoint inhibitory concentrations. Nevertheless, the results show that inhibition of nuclear export is an alternative to checkpoint kinase inhibition for abrogating the G(2) checkpoint and they should stimulate the search for less toxic nuclear export inhibitors.

Tanzawaic acids M (1), N (2), O (3) and P (4) and the known tanzawaic acids B (5) and E (6), have been isolated from an extract of a cultured marine-derived fungus (strain CF07370) identified as a member of the genus Penicillium. The structures of 1–4 were determined based on spectroscopic evidence. The antimicrobial and cytotoxic activities of compounds 1–6 were evaluated.

This work was supported by the Spanish Ministerio de Ciencia e Innovacion (MICINN) (SAF2009‐0839). F. C. acknowledges financial support from the Programa JAE‐Pre (CSIC). A.R. D.‐M. acknowledges funding from the IMBRAIN project (FP7‐REGPOT‐2012‐CT2012‐31637‐IMBRAIN). The Government of Panama granted permission for the collection of the samples. C. C. is supported by a “Waxweiler grant for cancer prevention research” from the Action LIONS Vaincre le Cancer. This work was also supported by Televie Luxembourg, the Recherche Cancer et Sang foundation, and the Recherches Scientifiques Luxembourg association. The authors thank the Een Haerz fir Kriibskrank Kanner association and the Action LIONS Vaincre le Cancer for generous support. Further support was received from the European Union (EU) (ITN “RedCat” 215009 and Interreg IVa project “Corena”). M. D. was supported by the Korean National Research Foundation (NRF), MEST [Tumor Microenvironment Global Core Research Center (GCRC), grant number 2012‐0001184].

Diabetes is a consequence of a decrease on functional β-cell mass. We have recently demonstrated that epoxypukalide (Epoxy) is a natural compound with beneficial effects on primary cultures of rat islets. In this study, we extend our previous investigations to test the hypothesis that Epoxy protects β-cells and improves glucose metabolism in STZ-induced diabetic mice. We used 3-months old male mice that were treated with Epoxy at 200 μg/kg body weight. Glucose intolerance was induced by multiple intraperitoneal low-doses of streptozotocin (STZ) on 5 consecutive days. Glucose homeostasis was evaluated measuring plasma insulin levels and glucose tolerance. Histomorphometry was used to quantify the number of pancreatic β-cells per islet. β-cell proliferation was assessed by BrdU incorporation, and apoptosis by TUNEL staining. Epoxy treatment significantly improved glucose tolerance and plasma insulin levels. These metabolic changes were associated with increased β-cell numbers, as a result of a two-fold increase in β-cell proliferation and a 50% decrease in β-cell death. Our results demonstrate that Epoxy improves whole-body glucose homeostasis by preventing pancreatic β-cell death due to STZ-induced toxicity in STZ-treated mice., This work was supported by grants from: Programa Ramón y Cajal (RYC-2011-08101) Ministerio de Economía y Competitividad (Spain); Sociedad Española de Diabetes Basic Research Grant (2014) to IC.

Tanzawaic acids M (1), N (2), O (3) and P (4) and the known tanzawaic acids B (5) and E (6), have been isolated from an extract of a cultured marine-derived fungus (strain CF07370) identified as a member of the genus Penicillium. The structures of 1–4 were determined based on spectroscopic evidence. The antimicrobial and cytotoxic activities of compounds 1–6 were evaluated., This work was supported by the Ministerio de Ciencia e Innovación SAF2009–0839. F. C. acknowledges financial support from Programa JAE-Pre (CSIC). ARDM acknowledges funding from the IMBRAIN project (FP7-REGPOT-2012-CT2012–31637-IMBRAIN). CC is supported by a “Waxweiler grant for cancer prevention research” from the Action Lions “Vaincre le Cancer”, Luxembourg. This work was supported by Télévie Luxembourg, the “Recherche Cancer et Sang” foundation and “Recherches Scientifiques Luxembourg” association. The authors thank the “Een Häerz fir Kriibskrank Kanner” association and the Action Lions “Vaincre le Cancer” for generous support. MD is supported by the National Research Foundation (NRF) by the MEST of Korea for Tumor Microenvironment Global Core Research Center (GCRC) grant, [grant number 2012–0001184].

The rearranged compound 1, the regular 2 and 3 and the degraded 4 are novel bisabolene-type metabolites that along with the known compounds caespitol, 8-acetylcaespitol, caespitane, caespitenone, laucapyranoid A, and furocaespitane have been isolated from the sea hare Aplysia dactylomela. The structures of these compounds were determined on the basis of spectroscopic evidence. The irregular network of 1 suggested that the halogenated epoxide 6 is a key intermediate for a unified biogenetic pathway of naturally occurring marine algal bisabolene-type metabolites.

[structure: see text] Neopetrosiamdes A (1) and B (2), two diastereomeric tricyclic peptides that inhibit amoeboid invasion of human tumor cells, have been isolated from the marine sponge Neopetrosia sp. collected in Papua New Guinea. The structures of the neopetrosiamides were elucidated by analysis of MS and NMR data and confirmed by chemical degradation.

A biogenetically interesting halogen-devoid metabolite chamigrenelactone 1, with a high oxygen-content, has been isolated from Laurencia obtusa from Isla Grande (Caribbean Panama). Its structure and stereochemistry were determined on the basis of spectral studies.

Two novel sesterterpenes 1 and 2 have been isolated from the Antarctic sponge Suberites caminatus. Their structures and relative stereochemistries were determined by spectroscopic methods. Compound 1 features a novel structural type of suberitane network, and an epimer of compound 2 seems to be the biogenetic precursor of 1 and suberitenones A and B. The exclusive prevalence of suberitane-derived sesterterpene metabolites in species of Suberites suggests that this skeleton may be a chemical marker of the genus.

5 pages, 3 tables, 1 chart.-- PMID: 12428955 [PubMed].-- Printed version published Nov 20, 2002., Supporting information available: Table showing the phytotoxic effects of compounds 11-13 on barley and tomato leaves.-- Available at: http://pubs.acs.org/doi/suppl/10.1021/jf025857p?cookieSet=1, In this work the antifeedant effects of the halogenated monoterpenes 1−13 were tested against several divergent insect species. These compounds have been isolated from Plocamium cartilagineum (6 was isolated as an acetyl derivative), except for 4, which was isolated from Pantoneura plocamioides. We have also included the semisynthetic derivatives 1a, 2a, and 7. Compounds 1, 1a, 2, 4, 5, 7, 8−10, and 13 were antifeedants against Leptinotarsa decemlineata with varying potencies. The aphids Myzus persicae and Ropalosiphum padi were strongly deterred in the presence of compounds 2, 12, and 13. This effect was correlated with the electronic recording of their probing behavior. Compounds 2 and 12 were toxic to L. decemlineata and had selective cytotoxicity to insect-derived Sf9 cells. None of the tested compounds showed phytotoxic effects. The antifeedant and cytotoxic effects of these compounds were compared with those of the polyhalogenated insecticide γ-hexachlorocyclohexane (lindane)., A.R.D.-M., M.C., O.S., and A.G. acknowledge I3P-CSIC (predoctoral and postdoctoral), AECI (predoctoral), and MEC/Contrato de Reincorporación Fellowships. This work was partially supported by Convenio CSIC-U.Chile and Grants FONDECYT 1990935, Instituto Antártico Chileno (INACH), MCYT-Spain (BQU2001-1505; PPQ2002-02494), and CYTED IV.13.

4 pages, 1 figure, 2 tables.-- PMID: 11975508 [PubMed].-- Printed version published Apr 26, 2002., Three new minor linear polyhalohydroxylated marine monoterpenes, plocamenols A−C (1−3), have been isolated from the red alga Plocamium cartilagineum. The structure and relative stereochemistry of these compounds were determined on the basis of spectroscopic evidence., This work was supported by Programa Antártico Español (MCYT), FEDER (projects: 1FD97-0348- C03-03), FONDECYT (1990935), Subdirección General de Cooperación Internacional, and the Program of Cooperation between the Consejo Superior de Investigaciones Científicas (CSIC, Spain)-Universidad de Chile. A.R.D.-M. acknowledges a fellowship from the CICYT.

The electrophoretic behavior in polyacrylamide gels of the acidic polysaccharides produced by the soil bacteria Bradyrhizobium (Chamaecytisus) strain BGA1 and Bradyrhizobiumjaponicum USDA1 10 has been studied. Both polysaccharides were polydisperse, producing a ladder-like pattern after fixation with Alcian Blue and silver staining of the gel. The polysaccharide molecules were separated according to their size, and they behaved as a collection of flexible random coils of different size and similar charge/mass ratio. The electrophoretic behavior was not affected by the presence of acetyl groups in the polysaccharide. The range of molecular weights of the exopolysaccharide produced by B. japonicum USDA110 was wider and with larger molecules than that of the polysaccharide produced by strain BGA1. The resolution was dependent on the electrophoresis buffer; the best results were achieved with Tris-borate; in Tris-glycine buffer, the resolution was worse, and it was not improved by the addition of sodium dodecyl sulfate (SDS).

This is an open-access article distributed under the terms of the Creative Commons Attribution License., There is an urgency to find new treatments for the devastating epidemic of diabetes. Pancreatic b-cells viability and function are impaired in the two most common forms of diabetes, type 1 and type 2. Regeneration of pancreatic b-cells has been proposed as a potential therapy for diabetes. In a preliminary study, we screened a collection of marine products for b-cell proliferation. One unique compound (epoxypukalide) showed capability to induce b-cell replication in the cell line INS1 832/ 13 and in primary rat cell cultures. Epoxypukalide was used to study b-cell proliferation by [3H]thymidine incorporation and BrdU incorporation followed by BrdU/insulin staining in primary cultures of rat islets. AKT and ERK1/2 signalling pathways were analyzed. Cell cycle activators, cyclin D2 and cyclin E, were detected by western-blot. Apoptosis was studied by TUNEL and cleaved caspase 3. b-cell function was measured by glucose-stimulated insulin secretion. Epoxypukalide induced 2.5- fold increase in b-cell proliferation; this effect was mediated by activation of ERK1/2 signalling pathway and upregulation of the cell cycle activators, cyclin D2 and cyclin E. Interestingly, epoxypukalide showed protection from basal (40% lower versus control) and cytokine-induced apoptosis (80% lower versus control). Finally, epoxypukalide did not impair b-cell function when measured by glucose-stimulated insulin secretion. In conclusion, epoxypukalide induces b-cell proliferation and protects against basal and cytokine-mediated b-cell death in primary cultures of rat islets. These findings may be translated into new treatments for diabetes. © 2013 López-Acosta et al., This work was supported by ISCIII-Subdireccion Geeneral de Evaluacion y Fomento de la Investigacion, Spain (PS09/00671 and CP08/00094), Europe-FP7 Marie Curie grant (IRG-247835) and Servicio Andaluz de Salud (PI-0256/2009).

In this work organic products were isolated and identified from a marine Bacillus sp. which presented growth inhibition of the pandemic strain of V. parahaemolyticus. The inhibitory products were extracted and characterized by spectroscopic and spectrometric techniques. Purification of the active products revealed five different diketopiperazines, which were compared with standards from high-performance liquid chromatography (HPLC). Although the diketopiperazines is not a finding of a new metabolite, the interested point or novelity of this work is the ability of diketopiperazines to inhibit the growth of pandemic strain of V. parahaemolyticus. We suggest the possibility of using this compound to reduce the growth and control the proliferation of pathogenic clones of V. parahaemolyticus that cause several problems in aquaculture industry.

Dactylomelatriol (1), obtained from the sea hare Aplysia dactylomela, is the first naturally occurring omphalane-derived sesquiterpene from the marine environment. From this species the known chamigrene and modified bisabolene sesquiterpenes 2-6 were also isolated. The structure and relative configuration of 1 were established by spectroscopic evidence. Its chemical structure is related to omphalic acid, the unique terrestrial-derived omphalane sesquiterpene isolated from a liverwort. A biogenetic route for this compound is proposed. The antimicrobial activities of compounds 1-6 were evaluated against a panel of microorganisms., This work was supported by the Ministerio de Ciencia e Innovación (BIO2007-61745, SAF2009-08039, SAF2010-16858) and DGUI Gobierno de Canarias (PIO42005, PUB2005/030). We gratefully acknowledge A. Corrales for her technical support of this project.

3 pages, 3 figures, 1 table.-- PMID: 12088448 [PubMed].-- Printed version published Jun 28, 2002., Supporting information (2 pages) available at: http://pubs.acs.org/doi/suppl/10.1021/np010580t, Two new sesquiterpenes belonging to a novel oxacyclic structural type of chamigrene skeleton, oxachamigrene (1) and 5-acetoxyoxachamigrene (2), have been isolated from the red alga Laurencia obtusa. The structures of the compounds were determined on the basis of spectroscopic evidence. A biogenetic route for these metabolites has been proposed., This work was supported by Ministerio de Ciencia y Tecnología (MCYT), FEDER (project 1FD97-0348- C03-03), Subdirección General de Cooperación Internacional, Program of Cooperation between the Consejo Superior de Investigaciones Científicas (CSIC, Spain)-Universidad de Chile and the collaboration of CEBIMAR of Cuba. I.B. acknowledges a grant from the CICYT.

Six guaiane sesquiterpenes recurvatiane A-F, including the previously known recurvatiane E and xanthomicrol, were isolated from the Andean Perezia recurvata and their structures determined by spectroscopic evidence. The absolute stereochemistry of recurvatiane A was established by derivatization with (R)- and (S)-α-methoxy-α-phenylacetic acids (MPA). The suite of guaiane-based metabolites here reported, which we have named recurvatianes A-F, provide an example of a pathway by which molecular diversity is generated by the occurrence of specific oxidation reactions in the late biosynthetic steps of the frame structure., This work was supported by the Ministerio de Educación y Ciencia (BIO2007-61745, SAF2009-08039, SAF2010-16858). A.R.D.-M. would like to thank Programa JAE-Doc (CSIC) for financial support.

Two new steroids (1 and 2) and the known pregna-1,4,20-trien-3-one (3) have been isolated from the Pacific octocoral Carijoa multiflora. Compound 1 possesses a novel spiropregnane-based steroidal skeleton. The photochemical transformation of 3 into 1 allowed the assignment of the absolute configuration at C-10 of 1. The antibacterial activities of compounds 1 and 3 were evaluated against a panel of bacterial strains., his work was supported by the Ministerio de Ciencia e Innovación (BIO2007-61745, SAF2009-08039, SAF2010-16858). A.R.D.-M. acknowledges financial support from Programa JAE-Doc (CSIC).

Five new bafilomycins, F (1) to J (5), have been isolated from laboratory cultures of two Streptomyces spp. obtained from marine sediments collected in British Columbia, and their structures have been elucidated by detailed analysis of spectroscopic data and the synthesis of model compounds. The new bafilomycins F (1), G (2), H (3), and J (5) along with several co-occurring known analogues showed potent inhibition of autophagy in microscopy and biochemical assays. The thiomorpholinone fragment present in bafilomycin F (1) has not previously been found in a natural product.

The cembranoid 1 and the furanocembranolides 2–4 along with the known pukalide were isolated from Leptogorgia sp. and their structures determined spectroscopically. The 1,4-diketo-cembranoid 1 follows an oxidation pattern of C-18 that reinforces the concept of oxidation profile of C-18 as taxonomical marker for octocorals. The co-occurrence within a species of furanocembranolide/1,4-diketo-cembranoid congeners 1/2–4 raises the question about which one is the biogenetic precursor. A biogenetic pathway is proposed.

2 pages, 1 figure, 1 table.-- Article in press., Supporting information available: Figures and NMR spectra of compounds 1 and 2.-- Available at: http://pubs.acs.org/doi/suppl/10.1021/np9000976, Pronuciferine N-oxide (1), a proaporphine N-methyl-N-oxide alkaloid, along with the parent alkaloid pronuciferine (2) were isolated from Berberis coletioides. The structure of the new compound was determined by spectroscopic evidence. Compound 1 is the first naturally occurring proaporphinoid alkaloid with an N-oxide functionality., This work was supported by Universidad de Magallanes and Ministerio de Educación y Ciencia (BIO2007-61745, SAF2006-03004).

Bioassay-guided purification of an ethanolic extract of Cystoseira myrica against HEPG-2 (liver) and HCT116 (colon) human cancer cell lines led to the isolation of 3-keto-22-epi-28-nor-cathasterone, 1 and cholest-4-ene-3,6-dione, 2. This finding allowed us to report for the first time that a brassinosteroid-related metabolite occurs in seaweed. These compounds showed activity in the range of 12.38–1.16 μM with selective activity of compound 2 to liver cancer cell lines.

The structures and relative sterochemistry of three halogenated sesquiterpenoids gomerones A–C, 1 – 3 , isolated from Laurencia majuscula are described. They are representative of a novel carbon skeleton, gomerane, biogenetically derived from cyclization of a β-chamigrene precursor. A biogenetic relationship with related sesquiterpenoids from lower terrestrial plants Hepaticae of genera Bazzania , Mannia , Mylia , and Rebouli as well as higher plants of genera Cupressus and Juniperus has been established.

The crystal structure of N-methyl-1H- indole-2-carboxamide C10H10N2O was determined by single crystal X-ray diffraction. The structure can be described as consisting of an indole group and as substituent, linked at C2, the N-methylcarboxamide group. The molecular structure is essentially planar. The crystal packing results in N-H ------ O hydrogen bonds which join the molecules into centrosymmetric dimeric rings. The knowledge of the crystal structure allows a complete assignment of the ¹H and 13C-NMR spectra. The N-methyl-lH- indole-2-carboxamide is the first indole derivative isolated from marine fungus.

The family Trimusculidae produce labdane diterpenes, which differ in the degree and type of esterification with acetoxy and isovaleroyl ester, predominantly. In this article, we describe the isolation from the marine pulmonate Trimusculus peruvianus, collected on intertidal rocks of Chilean coasts, of two new labdane diterpenes closely related to the above mentioned characteristics. Their structures were determined by spectroscopic data and correspond to 6beta-hydroxy-labda-8, 13-dien-15-ol and 3, 19-isovaleroyl-6beta, 9alpha-dihydroxylabda-Delta(8,17), 13-dien-15-oic acid.

4 pages, 2 figures, 1 table, 1 scheme.-- Printed version published Nov 24, 2008., Supporting information (NMR spectra of gomerone, 13 pages) available at: http://dx.doi.org/10.1016/j.tet.2008.09.027, The structures and relative sterochemistry of three halogenated sesquiterpenoids gomerones A–C, 1–3, isolated from Laurencia majuscula are described. They are representative of a novel carbon skeleton, gomerane, biogenetically derived from cyclization of a β-chamigrene precursor. A biogenetic relationship with related sesquiterpenoids from lower terrestrial plants Hepaticae of genera Bazzania, Mannia, Mylia, and Rebouli as well as higher plants of genera Cupressus and Juniperus has been established., This work was supported by the Ministerio de Educación y Ciencia (BIO2007-61745, SAF2006-03004) and DGUI Gobierno de Canarias (PIO42005, PUB2005/030).

The new meroterpenoids avinosol (1), 3‘-aminoavarone (2), and 3‘-phenethylaminoavarone (3) have been isolated from the marine sponge Dysidea sp. collected in Papua New Guinea, and their structures were elucidated by analysis of spectroscopic data. Avinosol (1), which is apparently the first example of a naturally occurring meroterpenoid-nucleoside conjugate, showed antiinvasion activity in a cell-based assay.

6 pages, 5 tables, 2 schemes.-- Printed version published Sep 10, 2007.-- Supporting information (19 pages) available at: http://dx.doi.org/10.1016/j.tet.2007.06.080, The furanocembranolides 1–3 along with the known compounds pukalide, pukalidealdehyde, epoxypukalide, and leptolide were isolated from Leptogorgia spp. and their structures were determined by spectroscopic evidences. An NMR-based method using Pirkle's reagent at low temperature allowed us to determine the absolute configuration at C-10 of a γ-butenolide unit embedded in a flexible furanocembranolide network. The C-18 of furanocembranolides undergoes an oxidation cascade leading from a methyl group to a carboxylic acid/ester that appears to be genus specific. We introduce the concept genus-specific oxidation, a feature that provides a chemotaxonomical marker for several genera of octocorals. This concept also allowed us to propose a biogenetic pathway for these compounds., This work was supported by the MEC (BIO2007-61745, SAF2006-03004) and the DGUI Gobierno de Canarias (PI042005/003, PUB2005/030).

[structure: see text] The new meroterpenoids avinosol (1), 3'-aminoavarone (2), and 3'-phenethylaminoavarone (3) have been isolated from the marine sponge Dysidea sp. collected in Papua New Guinea, and their structures were elucidated by analysis of spectroscopic data. Avinosol (1), which is apparently the first example of a naturally occurring meroterpenoid-nucleoside conjugate, showed antiinvasion activity in a cell-based assay.

[structure: see text] Neopetrosiamdes A (1) and B (2), two diastereomeric tricyclic peptides that inhibit amoeboid invasion of human tumor cells, have been isolated from the marine sponge Neopetrosia sp. collected in Papua New Guinea. The structures of the neopetrosiamides were elucidated by analysis of MS and NMR data and confirmed by chemical degradation.

Secondary metabolites from pulmonate molluscs of the genera Siphonaria, Onchidium, and Trimusculus are described. Siphonaria and Onchidium biosynthesize mostly propionate-based metabolites whereas Trimusculus yields diterpene derivatives with a single type of labdane skeleton. The 42 regular polypropionates reported to date from Siphonaria are divided into two classes (class I, class II), based on their observed structural and stereochemical analogy. The strong resemblance between class I and cephalaspidean metabolites and between class II and onchidiid metabolites as well as the structural features of Trimusculus, in relation to the other pulmonates, encourage speculation about their biosynthetic and phylogenetic relationship. Class I metabolites could be suitable material to evidence that type I PKS modules are perhaps used iteratively in their biosynthesis.

A biogenetically interesting halogen-devoid metabolite chamigrenelactone 1, with a high oxygen-content, has been isolated from Laurencia obtusa from Isla Grande (Caribbean Panama). Its structure and stereochemistry were determined on the basis of spectral studies.

4 pages, 3 figures, 1 table.-- PMID: 15200327 [PubMed].-- Printed version published Jun 24, 2004., Supporting Information Available: 1H and 13C NMR spectra of carijenone 1 and experimental procedure.-- Available at: http://pubs.acs.org/doi/suppl/10.1021/ol049287l, An unprecedented biogenetically interesting bicyclic prostanoid 1, carijenone, has been isolated from the eastern Pacific octocoral Carijoa multiflora. The C-12 oxygenated function, characteristic of the coral cyclopentanone fatty acid derivatives, is involved in the formation of a five-membered oxane ring fused to the cyclopentane network. Its structure and stereochemistry were determined on the basis of spectral studies and molecular mechanics calculations., This work was supported by the MCYT (PPQ2002-02494), DGUI of the Canary Islands Government (PI2002/044) and CYTED. The STRI provided support and facilities. M. Gupta, J. del Rosario, and D. Macías provided technical support. The Government of the Republic of Panama granted permission for the collection of the samples.

The soil bacterium Bradyrhizobium (Chamaecytisus) strain BGA-1 produces an extracellular polymeric substance (EPS) that, in the presence of Fe(3+), Al(3+) or Th(4+) solutions, forms a gel-like precipitate composed of polysaccharide, protein, lipopolysaccharide and the metal. Precipitation of the main component of the EPS, the extracellular polysaccharide, and thorium was studied. The precipitate was stable, but redissolved at pH values below 3.0 or in the presence of 10 mM EDTA. In the precipitate, the ratio thorium/basic repeating unit of the polysaccharide ranged from 0.4 to 0.8 mol/mol. Soluble polysaccharide-thorium complexes were not found, and larger polysaccharide molecules were precipitated in preference to smaller ones. Kinetic studies showed a non-linear dependence of the precipitate on the concentrations of both thorium and polysaccharide. The behaviors of the purified polysaccharide and of whole EPS with the thorium-containing precipitate were compared. The results suggested that EPS components other than polysaccharide are able to modify the precipitating ability of the polysaccharide. Thus, whole EPS is a better substrate than the purified polysaccharide for the removal of thorium from its solutions.

Two unique chloro-pregnane steroids have been isolated from the eastern Pacific octocoral Carijoa multiflora and their structures and stereochemistries were determined on the basis of spectral studies and molecular mechanics calculations.

4 pages, 2 figures, 2 tables.-- Printed version published May 31, 2004., Two novel monoterpenes, 1 and 2, containing an unusual 1,2-bromochloro vinylic portion, were analyzed to study the influence of γ-substituents on the C-1 and H-1 chemical shifts of the 1,2-dihalo vinylic residue. This study reinforces the validity of the empirical rules based on 13C and 1H NMR spectroscopy as a helpful tool for determining the regio- and stereochemistry of substituted vicinal vinyl dihalides., This work was supported by the Ministerio de Ciencia y Tecnología (MCYT) projects REN2002-10485-E/ANT and PPQ2002-02494; DGUI of Canary Islands Government project PI2002/044 and by the Instituto Antártico Chileno (INACH).

6 pages, 1 figure, 2 tables, 1 scheme.-- Available online Dec 30, 2003., New degraded and rearranged diterpenoids, 5–8, have been isolated from the Antarctic sponge Dendrilla membranosa. The structure and relative stereochemistry of these compounds were determined by spectroscopic data. The absolute stereochemistry of 5 was determined by spectroscopic data using a chiral reagent. Conformational studies allowed us to assign also the absolute stereochemistry of 6–8, as well as those previously isolated spongian-derived metabolites with known relative stereochemistries., This work was supported by Ministerio de Ciencia y Tecnología (MCYT, projects: REN2002-10485-E/ANT and PPQ2002-02494), Instituto Antártico Chileno (INACH), and DGUI (Gobierno de Canarias: PI2002/044). A.R.D.-M. acknowledges an I3P grant from the CSIC and E.D. acknowledges a fellowship (FPI) from the CICYT.

Summary The thorium effect on Bradyrhizobium growth was assayed in liquid media. Th4+ inhibited the growth of Bradyrhizobium (Chamaecytisus) BGA-1, but this effect decreased in the presence of suspensions of live or dead bacterial cells. Th4+ induced the formation of a gel-like precipitate when added to a dense suspension of B. (Chamaecytisus) BGA-1 cells. Viable Bradyrhizobium cells remained in suspension after precipitate formation. Thorium was recovered in the precipitate, in which polysaccharide, lipopolysaccharide and proteins were also found. After Th4+ addition, the morphology of B. (Chamaecytisus) BGA-1 or Bradyrhizobium japonicum USDA 110 sedimented cells studied by scanning electron microscopy changed from an entangled network of capsulated bacteria to uncapsulated individual cells and an amorphous precipitate. Energy-dispersive X-ray spectroscopy showed that thorium was mainly in the amorphous fraction. Precipitate was also formed between B. (Chamaecytisus) BGA-1 and Al3+, which was also toxic to this bacterium. Precipitate induced by Th4+ or Al3+ was found in all Bradyrhizobium and Sinorhizobium strains tested, but not in Rhizobium, Salmonella typhimurium, Aerobacter aerogenes or Escherichia coli. These results suggest a specific defence mechanism based on metal precipitation by extracellular polymers.

4 pages, 1 figure, 1 table.-- Printed version published Oct 14, 2002., Three new halogenated monoterpenes, 1–3, have been isolated from Plocamium cartilagineum. The structure and relative stereochemistry of these compounds were determined by spectroscopic data. Also the relative stereochemistry at C-7 for furoplocamioids A–C has been assigned., This work was supported by the Comisión Interministerial de Ciencia y Tecnología (CICYT), FEDER, MCYT (project PPQ2002-02494), Subdirección General de Cooperación Internacional and the Cooperation Programme between the Consejo Superior de Investigaciones Científicas (CSIC, Spain)-Universidad de Chile. A. R. D.-M. acknowledges a fellowship from the CICYT.