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Bioactivity-guided separation of the aqueous methanolic extract of Yucca desmettiana leaves, which in a preliminary screening exhibited significant molluscicidal activity, led to the isolation and structure elucidation of two new steroidal saponins (1 and 2). The structures of desmettianosides A and B, identified as bisdesmosidic furostanol glycosides with six and five sugar units, respectively, were established by detailed spectroscopic analyses of their NMR and MS data. Compounds 1 and 2 exhibited high molluscicidal activity against Biomphalaria alexandrina snails with LC100 values of 6 and 11 mg/L, respectively.

The ability of a crude onion peroxidase preparation to act as a biocatalyst for the oxidative dimerization–cyclization of methyl p-coumarate, methyl caffeate and methyl ferulate is presented. The products of the reaction have been fully characterized and were found to possess potent antioxidant activity in a ferric reducing antioxidant power (FRAP) assay.

Glandulaurencianols A and B were isolated from the organic extract of the red alga, Laurencia glandulifera, collected from the island of Crete in South Greece. Investigation of the mollusk, Aplysia punctata, collected from the coast of Nea Makri, Central Greece, resulted in the isolation of glandulaurencianols A and C. The structures of the new metabolites, as well as their relative configurations, were established on the basis of thorough analyses of their spectroscopic data.

Seventeen diterpenes featuring the dolabellane skeleton (1-17) were isolated from the organic extracts of the brown alga Dilophus spiralis. Seven compounds are new natural products (1, 3, 5, 6, 11, 14, 15) and eight are structurally revised (2, 4, 7-10, 12, 13), among which three are reported for the first time from a natural source (4, 9, 10). The structure elucidation and the assignment of the relative configurations of the isolated natural products were based on detailed analyses of their spectroscopic data. The structure of metabolite 10 was confirmed by single-crystal X-ray diffraction analysis, whereas the absolute configurations of compounds 2, 4-10, 12, and 13 were determined using the modified Mosher's method on the semisynthetic product 18 and chemical interconversions. The antibacterial activities of compounds 1-18 were evaluated against six strains of Staphylococcus aureus, including multidrug- and methicillin-resistant variants.

Seven new (1-7) and seven previously reported (8-14) halogenated metabolites were isolated from the organic extract of the Brazilian red alga Laurencia catarinensis. The structure elucidation and the assignment of the relative configurations of the new natural products were based on detailed NMR and MS spectroscopic analyses, whereas the structure of metabolite 6 was confirmed by single-crystal X-ray diffraction analysis. The absolute configuration of metabolite 1 was determined using the modified Mosher's method. The in vitro cytotoxicity of compounds 1-14 was evaluated against HT29, MCF7, and A431 cell lines.

Seven new diterpenes, featuring the rare 2,6-cyclo-xenicane skeleton, along with eleven previously reported metabolites were isolated from the organic extracts of the brown algae Dilophus fasciola and Dilophus spiralis. The structure elucidation of the isolated natural products was based on detailed analyses of their spectroscopic data (NMR, MS, IR, UV), whereas the assignment of their relative configurations was assisted by molecular modelling studies.

Examination of the digestive and hermaphroditic glands' organic extract of the sea hare Aplysia fasciata yielded 16 metabolites, including eight sesquiterpenes, three diterpenes, and five C(15)-acetogenins. Among them, three sesquiterpenes, 6-hydroxy-1-brasilene (1), epibrasilenol acetate (2), and 6-epi-beta-snyderol (3), one acetogenin, (3Z,9Z)-7-chloro-6-hydroxy-12-oxo-pentadeca-3,9-dien-1-yne (4), and one diterpene, 16-acetoxy-15-bromo-7-hydroxy-9(11)-parguerene (5), are new natural products. The structure elucidation and the assignment of the relative configurations of the isolated natural products were established on the basis of extensive analyses of their spectroscopic data (NMR, MS, IR).

Three new (1, 4, 9) and nine previously reported (2, 3, 5-8, 10-12) 5alpha,8alpha-epidioxysterols were isolated from the organic extracts of the gorgonian Eunicella cavolini and the ascidian Trididemnum inarmatum. The structures and relative configurations of 1-12 were established on the basis of detailed NMR spectroscopic analyses and comparison with the literature. The growth inhibitory effects of 1-12 were evaluated against MCF-7 human breast cancer cells. Compound 1, bearing a cyclopropyl moiety in the side chain, exhibited the highest antiproliferative activity.

Four new natural products (1–4), along with three previously reported metabolites (5–7), all belonging to the pregnane class of steroids were isolated from the organic extract of the gorgonian Eunicella cavolini. The structures and relative configurations of the isolated compounds were determined through NMR spectroscopic techniques and chemical interconversions, while their absolute stereochemistry was determined using the modified Mosher's method. Activity evaluation of 1–7 towards MCF-7 human breast cancer cells showed partial growth inhibitory effects for all metabolites bearing an 11α-acetoxy moiety.

Five new dolastanes (1–5) were isolated from the brown alga Dilophus spiralis. The structural elucidation of the isolated compounds and the assignment of relative stereochemistry were based on analyses of their spectroscopic data. The structure proposed for 1 was confirmed by single crystal X-ray diffraction analysis, whereas its absolute stereochemistry was determined using the modified Mosher's method. The cytotoxicity of 1–4 was evaluated against seven cell lines.

Nature, the most prolific source of biological and chemical diversity, has provided mankind with treatments for health problems since ancient times and continues to be the most promising reservoir of bioactive chemicals for the development of modern drugs. In addition to the terrestrial organisms that still remain a promising source of new bioactive metabolites, the marine environment, covering approximately 70% of the Earth’s surface and containing a largely unexplored biodiversity, offers an enormous resource for the discovery of novel compounds. According to the MarinLit database, more than 27,000 metabolites from marine macro- and microorganisms have been isolated to date providing material and key structures for the development of new products in the pharmaceutical, food, cosmeceutical, chemical, and agrochemical sectors. Algae, which thrive in the euphotic zone, were among the first marine organisms that were investigated as sources of food, nutritional supplements, soil fertilizers, and bioactive metabolites.

The essential oils of the flower heads and leaves of Santolina rosmarinifolia L. (Compositae) cultivated in Romania were obtained through hydrodistillation and analysed by GC-MS. Forty-two components were identified, representing 92.3-94.0% of the whole composition of the samples. Their in vitro antimicrobial activity against gram-positive and gram-negative bacteria strains and the fungus Candida albicans was determined using the agar-diffusion method and the broth dilution method.

Novel fibrous biocomposites comprising ulvan, a sulfated polysaccharide extracted from the green seaweed Ulva rigida, and either polycaprolactone or polyethylene oxide were successfully prepared using the electrospinning technique. The morphology and the chemical composition of the nanofibers were characterized using SEM and FT-IR analyses. Ulvan was found to incorporate well with the co-electrospun biocompatible polymers, conferring on the collective properties of these materials. Such nanofibrous matrices represent potentially useful materials in the biomedical sector as tissue engineering scaffolds, wound dressings, or drug delivery systems. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42153.

Perezoperezone (1), curcuperezone (2), and diperezone (3), belonging to the rare class of bisabolane dimers, were isolated as minor constituents of the organic extract of the Caribbean soft coral, Pseudopterogorgia rigida. The structures of the new compounds 1 and 2 were established by detailed analyses of their NMR and MS data. 2013 Published by Elsevier Ltd.

Background: Salvia diterpenes have been found to have health promoting properties. Among them, carnosic acid and carnosol, tanshinones and sclareol are well known for their cardiovascular, antitumor, antiinflammatory and antioxidant activities. However, many of these compounds are not available at a constant supply and developing biotechnological methods for their production could provide a sustainable alternative. The transcriptome of S. pomifera glandular trichomes was analysed aiming to identify genes that could be used in the engineering of synthetic microbial systems. Results: In the present study, a thorough metabolite analysis of S. pomifera leaves led to the isolation and structure elucidation of carnosic acid-family metabolites including one new natural product. These labdane diterpenes seem to be synthesized through miltiradiene and ferruginol. Transcriptomic analysis of the glandular trichomes from the S. pomifera leaves revealed two genes likely involved in miltiradiene synthesis. Their products were identified and the corresponding enzymes were characterized as copalyl diphosphate synthase (SpCDS) and miltiradiene synthase (SpMilS). In addition, several CYP-encoding transcripts were identified providing a valuable resource for the identification of the biosynthetic mechanism responsible for the production of carnosic acid-family metabolites in S. pomifera. Conclusions: Our work has uncovered the key enzymes involved in miltiradiene biosynthesis in S. pomifera leaf glandular trichomes. The transcriptomic dataset obtained provides a valuable tool for the identification of the CYPs involved in the synthesis of carnosic acid-family metabolites. General Secretariat of Research and Technology (GSRT) {[}09-SYN-23-879]; grant SEE-ERA. NET PLUS {[}ERA 64/01]; grant KRIPIS {[}MIS 448840]

Dendritic-linear-dendritic (DLD) hybrids are highly functional materials combining the properties of linear and dendritic polymers. Attempts to electrospin DLD polymers composed of hyperbranched dendritic blocks of 2,2-bis(hydroxymethyl) propionic acid on a linear poly(ethylene glycol) core proved unsuccessful. Nevertheless, when these DLD hybrids were blended with an array of different biodegradable polymers as entanglement enhancers, nanofibrous nonwovens were successfully prepared by electrospinning. The pseudogeneration degree of the DLDs, the nature of the co-electrospun polymer and the solvent systems used for the preparation of the electrospinning solutions exerted a significant effect on the diameter and morphology of the electrospun fibers. It is worth-noting that aqueous solutions of the DLD polymers and only 1% (w/v) poly(ethylene oxide) resulted in the production of smoother and thinner nanofibers. Such dendritic nanofibrous scaffolds can be promising materials for biomedical applications due to their biocompatibility, biodegradability, multifunctionality, and advanced structural architecture. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 135, 45949.

Dilospiranes A and B (1 and 2), two diterpenes featuring unprecedented carbocycles, were isolated from the organic extract of the brown alga Dilophus spiralis, collected from the coast of Elafonissos Island, Greece. The structures and the relative configurations of the isolated natural products were determined on the basis of extensive analyses of their spectroscopic data.

Glandulaurencianols A and B were isolated from the organic extract of the red alga, Laurencia glandulifera, collected from the island of Crete in South Greece. Investigation of the mollusk, Aplysia punctata, collected from the coast of Nea Makri, Central Greece, resulted in the isolation of glandulaurencianols A and C. The structures of the new metabolites, as well as their relative configurations, were established on the basis of thorough analyses of their spectroscopic data.

Extracts from three Origanum species, including Origanum microphyllum, Origanum dictamnus and Origanum vulgare subsp. hirtum, native to the island of Crete (southern Greece), were partly fractionated through successive partition with ethyl acetate and n-butanol. All the fractions obtained were profiled with regard to their major polyphenolic constituents, using liquid chromatography-diode array-mass spectrometry. Furthermore, the antioxidant potency of each fraction was assessed by estimating the antiradical activity (A(AR)) and the hydroxyl free radical scavenging activity (SA(HFR)). The chromatographic analyses revealed a rich profile mainly for the ethyl acetate fractions, composed principally by flavones, which were accompanied by a limited number of phenylpropanoids, flavanones and dihydroflavonols. The highest values of antioxidant activity were displayed by the ethyl acetate extract of O. dictamnus, which also possessed the richest polyphenolic composition.

The global metabolic profile of Laurencia crude red algal extracts was addressed by applying high-throughput analytical techniques, namely UHPLC–PDA–HRMS and 2D HSQC NMR. An integrated platform including software tools and databases, such as Xcalibur, ToxID, ACD/Labs and MarinLit, has been developed to mine the complex analytical data towards the accelerated identification of known metabolites and the detection of new natural products at the early stages of phytochemical analysis. In parallel, a searchable ‘in-house’ Laurencia-focused NMR database incorporating chemical structures, NMR spectroscopic data and reported biological activities has been generated. The screening strategy has been developed as a tool to prioritize the crude extracts to be further subjected to phytochemical analysis by tracing the presence of new natural products among the pool of known compounds. The successful application of this integrated methodology in the crude extract of Laurencia chondrioides led to the rapid detection of two new C15 bromoallene acetogenins (1 and 2), which were subsequently isolated and characterized.

Parnapimarol (1), a new pimarane diterpene, along with nepetaparnone (2) and nepetanudone (3), one new and one previously reported nepetalactone dimer, respectively, were isolated from the dichloromethane extract of the aerial parts of Nepeta parnassica, collected on Mt. Parnassos, Greece. The structures and relative configurations of 1-3 were determined on the basis of their spectroscopic characteristics (1D and 2D NMR, IR, MS). The structure of 2 was confirmed by single-crystal X-ray diffraction analysis. The insecticidal activity of 1-3 against ants and mosquito larvae was also evaluated.

Terpenes have numerous applications, ranging from pharmaceuticals to fragrances and biofuels. With increasing interest in producing terpenes sustainably and economically, there has been significant progress in recent years in developing methods for their production in microorganisms. In Saccharomyces cerevisiae, production of the 20-carbon diterpenes has so far proven to be significantly less efficient than production of their 15-carbon sesquiterpene counterparts. In this report, we identify the modular structure of geranylgeranyl diphosphate synthesis in yeast to be a major limitation in diterpene yields, and we engineer the yeast farnesyl diphosphate synthase Erg20p to produce geranylgeranyl diphosphate. Using a combination of protein and genetic engineering, we achieve significant improvements in the production of sclareol and several other isoprenoids, including cis-abienol, abietadiene and β-carotene. We also report the development of yeast strains carrying the engineered Erg20p, which support efficient isoprenoid production and can be used as a dedicated chassis for diterpene production or biosynthetic pathway elucidation. The design developed here can be applied to the production of any GGPP-derived isoprenoid and is compatible with other yeast terpene production platforms.

The dichloromethane-methanol extract, the essential oil obtained by hydrodistillation from Nepeta parnassica, and the isolated 4aα,7α,7aβ-nepetalactone were evaluated for their repellent effect against the mosquitoes Aedes (Stegomyia) cretinus Edwards and Culex pipiens pipiens biotype molestus Forskal. The chemical analysis of N. parnassica essential oil, dominated by oxygenated monoterpenes (87 %), revealed 4aα,7α,7aβ-nepetalactone (36.8 %), 1,8-cineole (25.5 %), and 4aα,7β,7aβ-nepetalactone (11.1 %) as the major constituents. The results of the insect bioassays showed that the essential oil and the dichloromethane-methanol extract of N. parnassica were very active against Aedes cretinus for up to 3 h and against Culex pipiens for up to 2 h post application. The isolated 4aα,7α,7aβ-nepetalactone showed very high mosquito repellency for periods of at least 2 h against both species.

The bioactive metabolites derived from weeds have attracted the interest of the food and pharmaceutical industries due to their health benefits.To evaluate the anti-oxidant and acetylcholinesterase activity of Dittrichia viscosa extracts and characterise the polyphenolic metabolites using the LC coupled with diode-array detection (DAD) and positive mode electrospray ionisation (ESI) MS method with a view to evaluating the exploitation potential of this invasive weed.Roots and aerial parts of D. viscosa were extracted with solvents of increasing polarity and their major polyphenolic metabolites were identified by LC - DAD/ESI(+)/MS. The total phenolic content of the extracts was determined using the Folin-Ciocalteu method, while their anti-oxidant activity was evaluated on the basis of their ability to scavenge the stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydrogen peroxide. Thin-layer chromatography was used to screen for acetylcholinesterase inhibitors.Stem extracts gave the highest phenolic content, whereas the roots showed the lowest content. Twenty-five polyphenolic constituents of the extracts were tentatively characterised according to their MS and UV spectroscopic data. Among the extracts studied, roots-ethyl acetate and flowers-diethyl ether revealed the highest activity according to the DPPH and chemiluminescence assays respectively.The metabolic profile of D. viscosa was studied and the structures of the major polyphenolic metabolites were tentatively assigned based on their MS and UV-vis spectra. The extracts exhibited high levels of anti-oxidant and acetylcholinesterase inhibitory activity and the inhibitors are probably localised mainly in flowers and roots.

Macroalgae are a significant source of extracellular organic material in the coastal areas of the Mediterranean, including organic ligands which serve as modulators of metal complexing capacity. This paper examines the release of copper-complexing ligands by 24 macroalgal species, including chlorophyta, rhodophyta, ochrophyta as well as Posidonia oceanica, common throughout the Mediterranean. Metabolites isolated from the algae Dictyota dichotoma and Pterocladiella capillacea were examined for the first time regarding their Cu-complexing properties. The concentration of ligands (LT) and the copper-binding strength (log Kapp) of exudates and metabolites were determined by electrochemical methods. All algal species released ligands giving LT concentrations ranging from 109 to 744 nM in unfiltered samples. An increase in the concentration of ligands up to 15 times in comparison to the blank was observed after 48 h of culturing macroalgae in artificial seawater. The binding strength (log Kapp) varied among species from 7.0 to 8.6, except for the metabolites for which it was lower (log Kapp = 6). Most of the ligands released were in the dissolved phase, with the contribution of particulate and/or colloidal organic matter (up to 46% of total ligands) appearing to be important only in specific macroalgal species.

Phytochemical analyses of weeds, many of which have been used in traditional medicine worldwide, could lead to the identification of secondary metabolites with significant biological activity.To perform an assessment of the chemical composition and exploitation potential of the invasive weed Oxalis pes-caprae. To evaluate the anti-oxidant activity of its extracts and isolate and characterise polyphenolic metabolites using LC-DAD-MS (ESI+) and NMR methods.Aerial parts of the invasive weed O. pes-caprae were extracted with solvents of increasing polarity and their major polyphenolic metabolites were identified by LC-DAD-MS (ESI+). The total phenolic content of the extracts was determined using the Folin-Ciocalteu method, while their anti-oxidant activity was evaluated on the basis of their ability to scavenge the stable free radical 1,1-diphenyl-2-picrylhydrazyl and hydrogen peroxide.The major polyphenolic constituents of the extracts were tentatively characterised as chlorogenic acid, quinic ferulate, luteolin glucoside and cernuoside according to their MS and UV spectroscopic data. Cernuoside, an aureusidin glucoside, was isolated from the methanolic extract of the weed's flowers and its structure was unambiguously identified by 1D- and 2D-NMR spectroscopy. The butanol extract of O. pes-caprae displayed the highest anti-oxidant activity.The metabolic profile of O. pes-caprae was studied and the structures of the major polyphenolic metabolites based on their MS and UV-vis spectra were tentatively assigned. The aureusidin glucoside cernuoside was isolated and characterised for the first time from O. pes-caprae. The extracts exhibited high levels of anti-oxidant activity.

The cytotoxic marine red algal metabolite thyrsiferol (1) was found to inhibit hypoxia-induced hypoxia-inducible factor-1 (HIF-1) activation in T47D human breast tumor cells (66% inhibition at 3 μM). Compound 1 also suppressed hypoxic induction of HIF-1 target genes (VEGF, GLUT-1) at the mRNA level, and displayed tumor cell line-selective time-dependent inhibition of cell viability/proliferation. Mechanistic studies revealed that 1 selectively suppressed mitochondrial respiration at complex I (IC50 3 μM). Thyrsiferol represents a prototypical, structurally unique electron transport chain inhibitor. The apparent rotenone-like activity may contribute to the observed cytotoxicity of 1 and play an important role in Laurencia chemical defense.

Summary •Triterpenes are plant secondary metabolites, derived from the cyclization of 2,3-oxidosqualene by oxidosqualene cyclases (OSCs). Here, we investigated the role of lupeol synthase, encoded by OSC3, and its product, lupeol, in developing roots and nodules of the model legume Lotus japonicus. •The expression patterns of OSC3 in different developmental stages of uninfected roots and in roots infected with Mesorhizobium loti were determined. The tissue specificity of OSC3 expression was analysed by in situ hybridization. Functional analysis, in which transgenic L. japonicus roots silenced for OSC3 were generated, was performed. The absence of lupeol in the silenced plant lines was determined by GC-MS. •The expression of ENOD40, a marker gene for nodule primordia initiation, was increased significantly in the OSC3-silenced plant lines, suggesting that lupeol influences nodule formation. Silenced plants also showed a more rapid nodulation phenotype, consistent with this. Exogenous application of lupeol to M. loti-infected wild-type plants provided further evidence for a negative regulatory effect of lupeol on the expression of ENOD40. •The synthesis of lupeol in L. japonicus roots and nodules can be solely attributed to OSC3. Taken together, our data suggest a role for lupeol biosynthesis in nodule formation through the regulation of ENOD40 gene expression.

International audience; The purification of the chloroform extract from the brown invasive macroalga Sargassum muticum, through a series of chromatographic separations, yielded 12 fractions that were tested against strains of bacteria, microalgae, and fungi involved in marine biofilm formation. The chemical composition of four (a, c, g, and k) out of the six fractions that exhibited anti-microfouling activity was investigated. Fraction a contained saturated and unsaturated linear hydrocarbons (C12-C27). Arachidonic acid was identified as the major metabolite in fraction c whereas fraction g contained mainly palmitic, linolenic, and palmitoleic acids. Fraction k was submitted to further purification yielding the fraction kAcaF1e that was composed of galactoglycerolipids, active against the growth of two of the four bacterial strains (Shewanella putrefaciens and Polaribacter irgensii) and all tested fungi. These promising results, in particular the isolation and the activity of galactoglycerolipids, attest the potential of the huge biomass of S. muticum as a source of new environmentally friendly antifouling compounds.

Four new 9,11-secosterols (2, 4-6), along with two previously reported ones (1, 3) were isolated from the organic extract of the gorgonian Eunicella cavolini. The structures and relative configurations of the isolated natural products were established on the basis of detailed NMR spectroscopic analysis. Metabolites 1 and 2 were found to strongly inhibit the growth of LNCaP human prostate adenocarcinoma cells and the estrogen-dependent growth of MCF-7 human breast adenocarcinoma cells.

Marine biota, even though the oceans are covering two thirds of earth’s surface, remains an unexplored source of new and exciting chemical structures. Systematic investigations on marine organisms started only forty years ago, but the results have already proven the impact of the significantly diverse conditions and the distinct evolution on their biosynthetic pathways that frequently yield complex molecules with no counterparts in the terrestrial environment. Seaweeds are among the first marine organisms chemically analyzed, with more than 3,600 articles published describing 3,300 secondary metabolites from marine plants and algae, and they still remain an almost endless source of new bioactive compounds. In this chapter, some of the major classes of seaweed metabolites which find applications in the industrial sector, such as carotenoids, phyco­colloids, polyunsaturated fatty acids and sterols, isolated either from aquacultures or wild harvesting, are presented. The ecological roles of a number of metabolites, as well as their potential application on the prevention of biofouling are described. The bioactive metabolites that target the pharmaceutical market, along with the spectrum of biological activities, are classified according to the class of producing seaweeds. The current status and the potential of seaweed metabolites for industrial exploitation is briefly discussed.