Search

Natural Products (NP) are essential for the discovery of novel drugs and products for numerous biotechnological applications. The NP discovery process is expensive and time-consuming, having as major hurdles dereplication (early identification of known compounds) and structure elucidation, particularly the determination of the absolute configuration of metabolites with stereogenic centers. This review comprehensively focuses on recent technological and instrumental advances, highlighting the development of methods that alleviate these obstacles, paving the way for accelerating NP discovery towards biotechnological applications. Herein, we emphasize the most innovative high-throughput tools and methods for advancing bioactivity screening, NP chemical analysis, dereplication, metabolite profiling, metabolomics, genome sequencing and/or genomics approaches, databases, bioinformatics, chemoinformatics, and three-dimensional NP structure elucidation., This publication is based upon work from COST Action CA18238 (Ocean4Biotech), funded by the European Cooperation in Science and Technology (COST) Program in the period 2019–2023. SPG: This work is financed by national funds from FCT—Fundação para a Ciência e a Tecnologia, I.P., in the scope of the projects UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences—UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy—i4HB. LLB: The publication is part of a project that has received funding from the Erasmus + Project No. ECOBIAS_609967-EPP-1-2019-1-RS-EPPKA2-CBHE-JP; GA.2019-1991/001-001. Development of master curricula in ecological monitoring and aquatic bioassessment for Western Balkans HEIs/ECOBIAS. CJ: This work was supported by grants PID2021-122732OB-C22 from MCIN/AEI/10.13039/501100011033/FEDER “A way to make Europe” (AEI, Spanish State Agency for Research and FEDER Programme from the European Union) and RTI2018-093634-B-C22 from the State Agency for Research (AEI) of Spain, co-funded by the FEDER Programme from the European Union, and BLUEBIOLAB (0474_BLUEBIOLAB_1_E), Programme INTERREG V A of Spain-Portugal (POCTEP). FP: This work is financed by national funds from FCT—Fundação para a Ciência e a Tecnologia, I.P., in the scope of the project UIDB/50006/2020 of the Research Unit on Associated Laboratory for Green Chemistry (LAQV) of the Network of Chemistry and Technology (REQUIMTE) and for an Assistant Research Position (CEECIND/01649/2021). MC: INTERREG-MAC2/1.1b/279 (AHIDAGRO) and the Ministerio de Ciencia e Innovación (Spain) (grant PID2020-115979RR-C32). ARDM is supported with funds from Proyecto Intramural Especial CSIC [Ref. 202280I032].

The present study investigated the effect of culture extracts (CB08035-SCA and CB08035-SYP) from Marinobacter hydrocarbonoclasticus (strain CB08035) on cell viability and the potential protective effects attributed to molecular mechanisms underlying antioxidant response to survive oxidative stress injuries. Caco-2 cells were submitted to oxidative stress by treatment with tert-butyl hydroperoxide (t-BOOH). Both extracts prevented cell damage and enhanced activity of antioxidant defenses (NQO1 and GST activities and GSH levels) reduced by treatment with t-BOOH. Increased ROS and caspase 3/7 activity induced by t-BOOH were dose-dependently prevented when cells were treated with the extracts. CB08035-SCA caused up-regulation of Nrf2, AKT1 and Bcl-2 gene expressions. Moreover, CB08035-SCA and CB08035-SYP treatments reduced significantly Bax, BNIP3, APAF1, ERK1, JNK1, MAPK1, NFκB1, TNFα, IL-6, IL-1β and HO-1 gene expressions of apoptosis, proinflammation and oxidative stress induced by t-BOOH. CB08035-SCA and CB08035-SYP CPE extracts confer a significant protection against oxidative insults to cells. Our results show that culture extracts CB08035-SCA and CB08035-SYP from M. hydrocarbonoclasticus (strain CB08035) appeared to have antioxidant potential, based on their ability to protect antioxidant enzymes and mRNA gene expressions linked to apoptosis/oxidative pathways. These results suggest that culture extracts CB08035-SCA and CB08035-SYP can be a potential ingredient in the pharmaceutical and cosmeceutical industries., This work was supported by the Project Ref. RTA2015-00010-C03(02-03) from the Ministerio de Economía, Industria y Competitividad, Spain.

Eighteen new oxysterols have been isolated from a previously undescribed octocoral collected from the eastern Pacific of Panama. Their structures were determined based on spectroscopic evidence. The absolute configuration was established by derivatization with (R)- and (S)-MPA. Antimicrobial and antileishmanial effects were evaluated., This work was supported by the Ministerio de Ciencia e Innovación (BIO2007-61745 and SAF2009-0839). F. C. acknowledges financial support from Programa JAE-Pre (CSIC). ARDM acknowledges funding from IMBRAIN project (FP7-REGPOT2012-CT2012-31637-IMBRAIN).

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 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.

In Alzheimer’s disease, the microtubule-associated protein tau forms intracellular neurofibrillary tangles (NFTs). A critical step in the formation of NFTs is the conversion of soluble tau into insoluble filaments. Accordingly, a current therapeutic strategy in clinical trials is aimed at preventing tau aggregation. Here, we assessed altenusin, a bioactive polyphenolic compound, for its potential to inhibit tau aggregation. Altenusin inhibits aggregation of tau protein into paired helical filaments in vitro. This was associated with stabilization of tau dimers and other oligomers into globular structures as revealed by atomic force microscopy. Moreover, altenusin reduced tau phosphorylation in cells expressing pathogenic tau, and prevented neuritic tau pathology induced by incubation of primary neurons with tau fibrils. However, treatment of tau transgenic mice did not improve neuropathology and functional deficits. Taken together, altenusin prevents tau fibrillization in vitro and induced tau pathology in neurons., This work has been funded by the National Health & Medical Research Council (NH&MRC 1037746, 1020562, 1083209) and the Australian Research Council (ARC 130102027) to L.M.I. A.C. was supported by Postdoctoral Fellowship CONICYT (74140034). L.M.I. is an NH&MRC Senior Research Fellow.

[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 new cyclic peptides, microsporins A and B (7 and 8), were isolated from culture extracts of the marine-derived fungus Microsporum cf. gypseum obtained from a sample of the bryozoan Bugula sp. collected in the U.S. Virgin Islands. The structures of the new compounds were determined by extensive interpretation of 2D NMR data and by chemical methods. Microsporins A and B are potent inhibitors of histone deacetylase and demonstrate cytotoxic activity against human colon adenocarcinoma (HCT-116), as well as against the National Cancer Institute 60 cancer cell panel. The total synthesis of microsporin A on solid-phase is also reported.

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].

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.

4 pages, 2 figures, 1 table, 1 scheme.-- Available online Dec 12, 2005.-- Supporting information (10 pages) available at: http://www.wiley-vch.de/contents/jc_2046/2006/o200500775_s.pdf, Side-chain-oxidized C-28-sterol 1 and one new pregnane metabolite 2 were isolated from eastern Pacific Muricea spp. The C-24(28)-epoxide functionality is a key intermediate in the C-24-dealkylation mechanism of the conversion of phytosterol to cholesterol by phytophagous insects. Certain marine invertebrates share this dealkylation pathway; however, such a key epoxide feature has not yet been found in a naturally occurring sterol from marine invertebrates. The unusual oxidation pattern of the side chain of 1 encourages speculation about its biogenesis and converts this non-zooxanthellate gorgonia into an interesting candidate organism for biosynthetic studies on C-24-dealkylation of phytosterols in octocorals. The (22S)-22-hydroxy group, after 24-dealkylation of 1, may be an advantageous functionalization in the side-chain cleavage to C-21-pregnane steroids in Muricea spp., This work was supported by the Ministerio de Educación y Ciencia (PPQ2002-02494), and the DGUI of the Canary Islands Government (PI2002/044). M. L. acknowledges MECESUP MAG0002, Chile, for financial support. The STRI provided support and facilities.

5 pages, 4 figures, 1 table.-- Printed version published Oct 3, 2005., Three naturally occurring pyranosyl-like polyhalogenated metabolites 1–3 as well as their likely biogenetic precursor, the linear compound 4, have been isolated from the red alga Ptilonia magellanica. They are the first compounds within the genus that incorporate chlorine in their network. Compound 3 have structural features reminiscent of the universal chemical signal AI-2 (autoinducer-2) for bacterial communication., This work was supported by the Ministerio de Educación y Ciencia (PPQ2002-02494, REN2002-10485-E/ANT), and the Gobierno de Canarias DGUI (PI2002/044). M.L. acknowledges MECESUP MAG0002, Chile, for financial support.

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.

Pantoneurotriols 1a and 2a are acyclic polyoxygenated monoterpenes isolated from the Antarctic endemism Pantoneura plocamioides together with compounds 3 and 4. The stereochemistries of these compounds were established by spectroscopic methods and pantoneurotriols have been proposed as biogenetic precursors of pantofuranoids, uncommon monoterpenes isolated from the same species. It was interesting to find compounds 4 and 5, metabolites first isolated from Plocamium cartilagineum, in a species belonging to a different order such as P. plocamioides.

Six new polyoxygenated marine monoterpenes have been isolated from the Antarctic alga Pantoneura plocamioides. The structure and relative stereochemistry of these compounds, denominated pantopyranoids A-C (1-3), and pantoisofuranoids A-C (4-6) were determined on basis of spectroscopic evidence.

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.

3 pages, 2 figures, 1 table.-- Printed version published Apr 1, 2002., A bromo sesquiterpene, bromocyclococanol 1, containing fused cyclopropane–cyclopentane rings leading a novel carbon skeleton has been isolated from the red alga Laurencia obtusa. The structure and stereochemistry were established by spectroscopic evidence and biogenetic considerations. A biogenetic route for this compound has also been proposed., The structure, configuration and possible biogenesis for bromocyclococanol 1 are described., 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 MCYT.

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).

The isolation and structure determination of a new chlorinated benzophenone antibiotic, pestalone (1), is described. The new compound was produced by a cultured marine fungus only when a unicellular marine bacterium, strain CNJ-328, was co-cultured in the fungal fermentation. The fungus, isolated from the surface of the brown alga Rosenvingea sp. collected in the Bahamas Islands, was identified as an undescribed member of the genus Pestalotia. The structure of 1, initially assigned with only modest confidence by combined spectral and chemical data, was confirmed by single-crystal X-ray analysis. Pestalone (1) exhibits moderate in vitro cytotoxicity in the National Cancer Institute's 60 human tumor cell line screen (mean GI(50) = 6.0 microM). More importantly, pestalone shows potent antibiotic activity against methicillin-resistant Staphylococcus aureus (MIC = 37 ng/mL) and vancomycin-resistant Enterococcus faecium (MIC = 78 ng/mL), indicating that pestalone should be evaluated in advanced models of infectious disease.

A new halogenated sesquiterpene has been isolated, together with five known compounds, from the red alga Laurencia claviformis, a species endemic to Easter Island. The structures were elucidated based on spectral analysis. The effect of these compounds on the inhibition of cytokinesis in the sea urchin Tetrapygus niger embryos was studied.

A bromo sesquiterpene, bromocyclococanol 1 , containing fused cyclopropane–cyclopentane rings leading a novel carbon skeleton has been isolated from the red alga Laurencia obtusa. The structure and stereochemistry were established by spectroscopic evidence and biogenetic considerations. A biogenetic route for this compound has also been proposed

A new sesterterpene epoxide-diol, aspergilloxide (1), was isolated from the extract of a cultured marine-derived fungus (strain CNM-713) identified as an undescribed member of the genus Aspergillus. The structure of 1 was determined by interpretation of NMR data and by chemical methods. The absolute stereochemistry of aspergilloxide was assigned by application of the modified Mosher method. The carbon skeleton of 1 represents a new addition to the architectural diversity of the sesterterpenoid (C25) class of secondary metabolites.

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.

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).

4 pages, 3 tables, 1 scheme.-- PMID: 17048828 [PubMed].-- Printed version published Oct 26, 2006., Supporting information available: 1H and 13C NMR spectra of 1-5, 1H NMR of the homoancepsenolide (7) complex with R- and S-TFAE, and experimental procedures.-- Available at: http://pubs.acs.org/doi/suppl/10.1021/ol061572c, Diastereomeric γ-dilactones isolated from Pterogorgia spp allowed the establishment of 13C NMR-based empirical rules to determine the relative stereochemistry of 3-alkyl-4-hydroxy-5-methyl-2(5H)-dihydrofuranones, γ-lactone moieties ubiquitous in many bioactive synthetic and natural products. An NMR-based method using Pirkle's reagent at low temperature allowed the absolute configuration of the naturally occurring dibutenolides to be unambiguously determined. A biogenetic pathway that involves oxidation of long-chain (C16:0 and C18:0) fatty acids is proposed., This work was supported by MEC (PPQ2002-02494, SAF2006-03004) and the DGUI Gobierno de Canarias (PI042005/003; PUB2005/030). The STRI provided facilities. Dr. M. Gupta, Lcdo. C. Vega (U de Panama), and J. del Rosario (STRI) provided technical support. The Government of Panama granted permission for the collection of the samples.

Four cytotoxic meroterpenoids, tropolactones A–D, were isolated from the whole broth extract of a marine-derived fungus of the genus Aspergillus. The structures of the meroterpenoids were established through a variety of two-dimensional NMR techniques. The absolute configuration of tropolactone A was determined using the modified Mosher method. Tropolactones A–C contain an interesting substituted 2,4,6-cycloheptatriene (tropone) ring, which presumably arises through an oxidative ring expansion from tropolactone D. Tropolactones A, B and C showed in vitro cytotoxicity against human colon carcinoma (HCT-116) with IC50 values of 13.2, 10.9 and 13.9 μg/mL., We appreciate the financial support provided by the NIH, National Cancer Institute under grant CA44848. M. Cueto acknowledges a postdoctoral fellowship from the Ministerio de Educacion of Spain.

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.

Compounds with three characteristic skeletons of members of the family Bonnemaisoneaceae were found to coexist in the alga Delisea fimbriata. The two new acetates 1 and 2a were also isolated; this is the first isolation of acetates from this genus. The structures, chemical transformation, and biogenetic significance of 1 and 2a are described.

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, 1 figure, 1 scheme.-- PMID: 15673253 [PubMed].-- Printed version published Feb 3, 2005., Supporting information (Spectral data and experimental procedures) available at: http://pubs.acs.org/doi/suppl/10.1021/ol0477428, Biogenetically interesting polypropionate-derived metabolites 1 and 2, featuring an unprecedented skeleton, have been isolated from the sea slug Elysia diomedea. Their enantiomeric character indicates that the current spontaneous electrocyclization cascade biogenetic hypothesis for the bicyclo[4.2.0]octane core must be enzymatically aided. These compounds are isomeric with the 15-nor-9,10-deoxytridachione/15-norphotodeoxytridachione pair of metabolites and encourage speculation about their biosynthetic relationship., This work was supported by the MEC (PPQ2002-02494) and the Canary Islands Government (PI2002/044). The STRI provided support and facilities. Dr. M. Gupta, Dr. J. A. Gómez, J. del Rosario, and D. Macías provided technical support. J. Maté received support from the U.S. NSF, Biological Oceanography Program (OCE- 9711529).

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.

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).