Aplysiasecosterol A: A 9,11‐Secosteroid with an Unprecedented Tricyclic γ‐Diketone Structure from the Sea Hare Aplysia kurodai

A new 9,11‐secosteroid having an unprecedented tricyclic γ‐diketone structure, aplysiasecosterol A ( 1 ), was isolated from the sea hare Aplysia kurodai. The structure was determined by one‐ and two‐dimensional NMR spectroscopic analysis, molecular modeling studies, a comparison of experimental and calculated ECD spectra, and a modified Mosher′s method. Aplysiasecosterol A ( 1 ) exhibited cytotoxicity against human myelocytic leukemia HL‐60 cells. A biosynthetic pathway for 1 from a known cholesterol was proposed and includes twice α‐ketol rearrangements and an intramolecular acetalization.     

New C15 Acetogenins from Two Species of Laurencia from the Aegean Sea

The chemical diversity of the approximately 1,200 natural products isolated from red algae of the genus Laurencia, in combination with the wide range of their biological activities, have placed species of Laurencia in the spotlight of marine chemists’ attention for over 60 years. The chemical investigation of the organic (CH₂Cl₂/MeOH) extracts of Laurencia microcladia and Laurencia obtusa, both collected off the coasts of Tinos island in the Aegean Sea, resulted in the isolation of 32 secondary metabolites, including 23 C₁₅ acetogenins (1–23), 7 sesquiterpenes (24–30) and 2 diterpenes (31 and 32). Among them, six new C₁₅ acetogenins, namely 10-acetyl-sagonenyne (2), cis-sagonenyne (3), trans-thuwalenyne C (4), tinosallene A (11), tinosallene B (12) and obtusallene XI (17), were identified and their structures were elucidated by extensive analysis of their spectroscopic data. Compounds 1–3, 5–11, 13 and 15–32 were evaluated for their antibacterial activity against Staphylococcus aureus and Escherichia coli.     

Arsenic Transformations in Short Marine Food Chains studied by HPLC-ICP MS

The chemical forms of arsenic in some herbivorous or mainly herbivorous marine animals and, in some cases, the algae on which they feed were determined by HPLC-ICP MS. In most cases arsenobetaine was present in the animals as well as arsenosugars consumed directly from the algae. However in the case of copepods Gladioferens imparipes fed only on the diatom Chaetoceros concavicornis which had been grown in axenic culture, arseno-betaine was absent. Arsenobetaine was also absent from the muscle of the silver drummer Kyphosus sydneyanus, although trimethyl-arsine oxide was present. This is the first reported case of the absence of arsenobetaine in a marine teleost fish and may be related to its fermentative faculty for digesting the macroalgae that it consumes. © 1997 by John Wiley & Sons, Ltd.     

Atmospheric Hydrocarbon Concentrations in the Baltic Sea Area

Abstract

During a marine research expedition in 1983 in the Baltic Sea area air samples were collected for the analysis of several organic and inorganic pollutants. The aim of the expedition was to obtain information on the airborne load in the sea as well as to measure the concentrations of the pollutants far away from source areas. In this paper the background concentrations of the primarily traffic originated aromatic hydrocarbons benzene, toluene and xylenes will be presented.

The concentrations of benzene were from 0.2 to 2μg/m³, of toluene between 0.4–3μg/m³, of m-xylene 0.02–0.60μg/m³ while the concentrations of o-xylene were 0.01–0.1 μg/m³. The concentrations did not depend too much on the origin (continental/sea type) of the air masses. A weak minimum in the concentrations of the measured hydrocarbons was noticed in the central Baltic Sea area. When comparing lead concentrations in fine particles (< 2.5 μm) with those of benzene, toluene and m-xylene some coincidence between them could be observed.     

Philinopsides A and B,Two New Sulfated Triterpene Glycosides from the Sea Cucumber Pentacta quadrangularis

Two new sulfated triterpene glycosides, philinopsides A ( 1 ) and B ( 2 ), were isolated from the sea cucumber Pentacta quadrangularis. Their structures were established by extensive spectral analysis (2D‐NMR and MS) and chemical evidence. Philinopside A ( 1 ) and B ( 2 ) showed significant cytotoxicity (ED₅₀ 0.75–3.50 μg/ml) against ten tumor cell lines. Compound 1 also significantly inhibited the proliferation, migration, and tube formation of human microvascular endothelial cells.     

Collaborative sampling trial in the context of quality assurance in the German marine monitoring programme for the North Sea and the Baltic Sea

This paper presents the assessment of a collaborative trial in sampling in the Baltic Sea in the framework of quality assurance in the German marine monitoring programme for the North Sea and the Baltic Sea. The objective of investigations was to determine the influence of sampling on analytical results for selected monitoring parameters and to harmonize the procedure for sampling of sea water to a large extent. In these studies the staff of three vessels took replicate sea water samples, 1 m below the surface and below the halocline, at two monitoring stations. Mass concentration mean values for different nutrient parameters were obtained from each sample, all in one laboratory. Data produced from the hierarchical design were treated with robust analysis of variance (ANOVA) to generate uncertainty estimates, as standard uncertainties (“u” expressed as standard deviation), for geochemical variation (s _geochem), primary sampling (s _sampling), and chemical analysis (s _analysis). Geochemical variation dominated the total variance in all cases. Sampling and analytical uncertainties contributed together up to 15% of the total variance and had a relative measurement uncertainty (u%) of less than 2% for all the parameters investigated. Thus for this study the sampling protocol and the analytical method could be regarded as fit-for-purpose. M. Gluschke was formerly affiliated to the Federal Environmental Agency, P.O. Box 33 00 22, 14191 Berlin, Germany.     

Structure elucidation of the new citharoxazole from the Mediterranean deep‐sea sponge Latrunculia (Biannulata) citharistae

Citharoxazole (1), a new batzelline derivative featuring a benzoxazole moiety, was isolated from the Mediterranean deep‐sea sponge Latrunculia (Biannulata) citharistae Vacelet, 1969, together with the known batzelline C ( 2 ). This is the first chemical study of a Mediterranean Latrunculia species and the benzoxazole moiety is unprecedented for this family of marine natural products. The structure was mainly elucidated by the interpretation of NMR spectra and especially HMBC correlations. Copyright © 2011 John Wiley & Sons, Ltd.     

Signal Substances and their Reception in the Sexual Cycle of Marine Brown Algae

Attraction and repulsion are responses to chemical stimuli which can be received and processed even by unicellular organisms without a morphologically defined nervous system. Chemical substances trigger off a chain of events which starts with a membrane-bound signal receptor and, after a sequence of regulatory and modulatory steps, ends in the modulation of a motor effector organ. Binding of the signal substances to the receptor produces conformational changes in which the receptor subunits are mutually dependent on one another, and also leads to chemical modification of the subunits and affects their molecular activity. These interactions, together with the characteristic type of movement, result in a physiological pattern of behavior which enables the flagellated sex cells (gametes) of marine brown algae to finally locate their partners. The simple but highly specific brown algae gamete systems have been investigated structurally and their biological activity analyzed. The signal substances are mainly highly unsaturated aliphatic or cyclic hydrocarbons with unsaturated side chains (general formula e. g. C₁₁H₁₄, C₁₁H₁₆, C₁₁H₁₈). These systems also serve as a simplifying model which helps in the understanding of complex ganglionic pathways in higher living organisms where the sense organs convey information from the surroundings to the central nervous system through nerve pathways. The information is then processed and answered, via efferent pathways, as movement.     

Isolation of New Polyketide Synthase Gene Fragments and a Partial Gene Cluster from East China Sea and Function Analysis of a New Acyltransfrase

Using the consensus-degenerate hybrid oligonucleotide primer polymerase chain reaction method, 26 new ketoacyl synthase (KS) fragments were isolated from a marine sediment sample in the East China Sea (ECS) and analyzed by construction of a phylogenetic tree. With a digoxigenin-labeled KS gene fragment used as a probe, a partial polyketide synthase (PKS) gene cluster was isolated and identified by hybridization screening of a marine sediment sample metagenome fosmid library constructed for this study. A new acyltransferase (AT) gene was cloned from the PKS gene cluster and heterogeneously expressed as a protein fused to maltose-binding protein (MBP). Ultraviolet spectrophotometry was used to study the binding of the MBP–AT fusion protein and single AT domain to substrates using MBP and bovine serum albumin as control proteins. Binding constants (Ka, per micromolar) were calculated and used to analyze the substrate specificity of the acyltransferase. We concluded that there are many unrevealed new PKS gene clusters in marine sediments in the ECS. The acyltransferase is presumably an acetyltransferase from a new PKS gene cluster.     

Extraction of climatic signals from fossil organic compounds in marine sediments up to 11.7 Ma old (IODP-U1318)

This study focuses on the extraction of climate signals and processes using a combined approach which includes the analysis of a high number of lipid molecules in marine sediments, and the chemometric analysis of the acquired data. Neutral and acidic fractions of marine sediments from site IODP-U1318 (south-west of the UK, Porcupine Seabight) were quantified by GC–MS. The alkenone unsaturation index, U^k′₃₇, was estimated from the composition of C₃₇ alkenones and it was then used for the estimation of sea surface temperatures (SST) for reference. Principal component analysis (PCA), explained 77.45% of the total data variance, and differentiated neutral fraction GC–MS total ion current (TIC) profiles according to SST values of the different sediment sections. GC–MS TIC chromatograms were correlated to sea surface temperatures (SST) by partial least squares regression (PLSR). The compounds more robustly in line with SST values at each sediment section explained 93% of the SST variance and they were identified using the variable importance in projection (VIP) scores method. The proposed approach enables an objective identification of organic compounds sensitive to SST variability throughout complete chromatographic profiles. As a result of this multivariate unbiased approach, lipid composition of sediments was differentiated between compounds of marine (long chain n-alkanes, long chain n-alkan-1-ols) and terrestrial (short chain n-alkan1-ols, alkenols, cholesterol, squalene) origin, whose concentrations were directly and inversely correlated to SST, respectively.     

Two new steroids with cytotoxicity from the marine sponge Dactylospongia elegans collected from the South China Sea

A new steroid, (3S,5R,9R,10S,13R,17R,20R,24S,22E)-ergosta-6,8,22-triene-3,25-diol (1), and its sulfonated analogue (2) together with a known one, 5α,8α-epidioxy-cholest-6-en-3β-ol (3) were isolated from the marine sponge Dactylospongia elegans collected from the South China Sea. The new structures including absolute configurations were established by the HRESIMS and 1D and 2D NMR analysis coupled with the X-ray crystal analysis. Both of 1 and 2 exhibited cytotoxicity against cancer cell line MCF-7 with IC₅₀ values of 9.7 and 8.5 μM, respectively.     

Ecological leads for natural product discovery: novel sesquiterpene hydroquinones from the red macroalga Peyssonnelia sp.

Pharmacologically-motivated marine natural product investigations have yielded a large variety of structurally unique compounds with interesting biomedical properties, but the natural roles of these molecules often remain unknown. While secondary metabolites may function as antimicrobial chemical defenses, few studies have examined this hypothesis. In the present investigation, chromatographic fractions from 69 collections of Fijian red macroalgae representing at least 43 species were evaluated for growth inhibition of three microbial pathogens and saprophytes of marine macrophytes. At least one microbe was suppressed by fraction(s) of all evaluated algae, suggesting that antimicrobial defenses are common among tropical seaweeds. From these leads, peyssonoic acids A-B (1-2), novel sesquiterpene hydroquinones, were isolated from the crustose red alga Peyssonnelia sp. At ecologically realistic concentrations, both compounds inhibited growth of Pseudoalteromonas bacteriolytica, a bacterial pathogen of marine algae, and Lindra thalassiae, a fungal pathogen of marine algae, and exhibited modest antineoplastic activity against ovarian cancer cells. The peyssonoic acids included one novel carbon skeleton and illustrated the utility of ecological studies in natural product discovery.     

A new meroterpenoid from the marine fungus Aspergillus versicolor (Vuill.) Tirab.

A new meroterpenoid asperdemin (1) and two known compounds, viz., diorcinol (2) and viridicatol (3), were isolated from the marine fungus Aspergillus versicolor. The structures of these compounds were established by NMR spectroscopy and high-resolution mass spectrome-try. The absolute stereochemistry of 1 was determined by modified Mosher’s method. The antimicrobial activity of the total extract from A. versicolor was attributed to diorcinol (2). Asperdemin exhibits weak cytostatic and membranolytic activities in developing embryos of the sea urchin Strongylocentrotus nudus.     

Aplyronines D–H from the sea hare Aplysia kurodai: isolation,structures, and cytotoxicity

Five cytotoxic macrolides, aplyronines D–H (4–8), were isolated from the Japanese sea hare Aplysia kurodai. They are new congeners of the antitumor compound aplyronine A (1), which was previously isolated from the same organism. Their structures were determined by spectroscopic analysis (NMR and MS). The cytotoxicity of these new compounds was evaluated in comparison with that of aplyronines A–C (1–3), suggesting the importance of the 7-O-seryl ester group for mediating the potent cytotoxicity of aplyronines.     

Unprecedented Quassinoids with Promising Biological Activity from Harrisonia perforata

Perforalactone A ( 1 ), a new 20S quassinoid with a unique cagelike 2,4‐dioxaadamantane ring system and a migrated side chain, was isolated from the plant Harrisonia perforata together with two biosynthetically related new quassinoids. The structures of these natural products were elucidated by NMR spectroscopy, X‐ray diffraction analysis, computational modeling, and the CD excitation chirality method. The compounds exhibited notable biological properties, including insecticidal activity against Aphis medicaginis Koch and antagonist activity at the nicotinic acetylcholine receptor of Drosophila melanogaster. The structural features of these compounds may be related to their promising biological characteristics. Their biosynthesis and an alternative origin of quassinoid‐type natural products are also discussed.     

The Absolute Configurations and Biogenesis of Some New Halogenated Chamigrenes from the Sea Hare Aplysia dactylomela

Four new halogenated chamigrenes have been isolated from the sea hare, the (E)- and (Z)-9-(bromomethylidene)-1,2,5-trimethylspiro[5.5]undeca-1,7-dien-3-ones ( 11 and 10 , resp.) the structures of which were deduced by NMR spectroscopy and by comparison with a known relative, the (8R,9R)-8-bromo-9-chloro-5,5,9-trimethyl-1-methylidenespiro[5,5]undec-3-en-2-one ( 12 ), and its (11 R)-11-acetoxy-substituted derivative 13 . Their structures and absolute configurations were determined and deduced by X-ray using the absolute-structure parameter. The configurations were remarkable in being enantiomeric to those of the tertiary chlorochamigrenes isolated so far. Consequently, a more general scheme is proposed to account for their biogenesis.     

Aplyronine A, a potent antitumor macrolide of marine origin, and the congeners aplyronines B and C: isolation, structures, and bioactivities

Aplyronine A (2), a potent antitumor macrolide was isolated from the sea hare Aplysia kurodai together with the congeners aplyronines B (3) and C (4). The absolute stereostructure of aplyronine A (2) was determined by the instrumental analysis (mainly NMR and MS) and the enantioselective synthesis of the fragments obtained from chemical degradation of aplyronine A (2). The structures of aplyronines B (3) and C (4) were also elucidated. Cytotoxicity and antitumor activity of aplyronine A (2) were evaluated.     

On the First Marine Stigmastane Sterols and Sterones Having a 24,25-Double Bond. Isolation from the Sponge Stelletta sp. of Deep Coral Sea

The sponge Stelletta sp. (Astrophorida, Stellettidae), collected at ?700 m in the Coral Sea, is shown to contain sterones and sterols of the stigmastane type with a C(24)?C(25) bond for which there is no precedent in the sea. Structure elucidation of the second abundant of these steroids, stigmasta-4,24(25)-dien-3-one ((+)- 1 ), is based on 1D and 2D NMR spectra and chemical transformation to acetate (?)- 5 . Stigmasta-4,24(25)-diene-3,6-dione ((?)- 3 ), present in trace amounts in the sponge, was obtained in sufficient quantity for NMR study by oxidation of the also present, inseparable, and abundant 4:1 mixture of stigmasta-5,24(25)-dien-3β-ol ( 6 ) and its 5,6-dihydro derivative 7 (Scheme 1). This oxidation also afforded the ketone analogues (+)- 8 and (+)- 9 , which could be separated, thus making structure elucidation possible. The 6β-hydroxystigmasta-4,24(25)-dien-3-one ((+)- 4 ), also present in trace amounts in the sponge, was obtained in sufficient amount for NMR study, together with its C(6) epimer (+)- 11 , by hydroperoxidation of (+)- 8 followed by deoxygenation (Scheme 2). The last trace steroid of the sponge, stigmasta-4,6,24(25)-trien-3-one ((?)- 2 ), was structurally elucidated using limited NMR data and comparison with the other stigmastanes. These stigmastanes, as the only steroids of this sponge, are likely to function as stabilizers of its cell walls; their phytosteroid structure, for a sponge which lives in the dark of deep waters, suggest origin through a complex food chain, possibly followed by bioelaboration in the sponge.     

Secondary Metabolites from Marine Sources with Potential Use as Leads for Anticancer Applications

The development of novel anticancer agents is essential to finding new ways to treat this disease, one of the deadliest diseases. Some marine organisms have proved to be important producers of chemically active compounds with valuable bioactive properties, including anticancer. Thus, the ocean has proved to be a huge source of bioactive compounds, making the discovery and study of these compounds a growing area. In the last few years, several compounds of marine origin, which include algae, corals, and sea urchins, have been isolated, studied, and demonstrated to possess anticancer properties. These compounds, mainly from securamines and sterols families, have been tested for cytotoxic/antiproliferative activity in different cell lines. Bioactive compounds isolated from marine organisms in the past 5 years that have shown anticancer activity, emphasizing the ones that showed the highest cytotoxic activity, such as securamines H and I, cholest-3β,5α,6β-triol, (E)-24-methylcholest-22-ene-3β,5α,6β-triol, 24-methylenecholesta-3β,5α,6β-triol, and 24-methylcholesta-3β,5α,6β-triol, will be discussed in this review. These studies reveal the possibility of new compounds of marine origin being used as new therapeutic agents or as a source of inspiration to develop new therapeutic agents.     

HPLC‐PAD‐atmospheric pressure chemical ionization‐MS metabolite profiling of cytotoxic carotenoids from the echinoderm Marthasterias glacialis (spiny sea‐star)

An HPLC‐PAD‐atmospheric pressure chemical ionization‐MS metabolite profiling analysis was conducted on the marine echinoderm Marthasterias glacialis (spiny sea‐star). Bio‐guided purification of the methanolic extract led to the isolation of several carotenoids, namely zeaxanthin, astaxanthin and lutein. These compounds were characterized using both UV–Vis characteristics and MS spectra interpretation. No previous works addressed the MS analysis of carotenoids present in this organism. The purified carotenoid fraction displayed a strong cell proliferation inhibition against rat basophilic leukemia RBL‐2H3 (IC₂₅=268 μg/mL) cancer cell line. Against healthy V79 (rat lung fibroblasts (IC₂₅=411 μg/mL)) cell line, however, toxicity was lower, as it is desired for anti‐cancer molecules. This study suggests that M. glacialis may constitute a good source of bioactive compounds that can be used as lead compounds for the pharmaceutical industry.