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Mar. Drugs, Volume 12, Issue 6 (June 2014), Pages 3091-3791

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Open AccessArticle Marine and Semi-Synthetic Hydroxysteroids as New Scaffolds for Pregnane X Receptor Modulation
Mar. Drugs 2014, 12(6), 3091-3115; doi:10.3390/md12063091
Received: 8 April 2014 / Revised: 29 April 2014 / Accepted: 30 April 2014 / Published: 27 May 2014
Cited by 4 | PDF Full-text (1032 KB) | HTML Full-text | XML Full-text
Abstract
In recent years many sterols with unusual structures and promising biological profiles have been identified from marine sources. Here we report the isolation of a series of 24-alkylated-hydroxysteroids from the soft coral Sinularia kavarattiensis, acting as pregnane X receptor (PXR) modulators. Starting
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In recent years many sterols with unusual structures and promising biological profiles have been identified from marine sources. Here we report the isolation of a series of 24-alkylated-hydroxysteroids from the soft coral Sinularia kavarattiensis, acting as pregnane X receptor (PXR) modulators. Starting from this scaffold a number of derivatives were prepared and evaluated for their ability to activate the PXR by assessing transactivation and quantifying gene expression. Our study reveals that ergost-5-en-3β-ol (4) induces PXR transactivation in HepG2 cells and stimulates the expression of the PXR target gene CYP3A4. To shed light on the molecular basis of the interaction between these ligands and PXR, we investigated, through docking simulations, the binding mechanism of the most potent compound of the series, 4, to the PXR. Our findings provide useful functional and structural information to guide further investigations and drug design. Full article
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Open AccessArticle Nine New and Five Known Polyketides Derived from a Deep Sea-Sourced Aspergillus sp. 16-02-1
Mar. Drugs 2014, 12(6), 3116-3137; doi:10.3390/md12063116
Received: 24 March 2014 / Revised: 12 April 2014 / Accepted: 16 April 2014 / Published: 27 May 2014
Cited by 10 | PDF Full-text (1547 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Nine new C9 polyketides, named aspiketolactonol (1), aspilactonols A–F (27), aspyronol (9) and epiaspinonediol (11), were isolated together with five known polyketides, (S)-2-(2′-hydroxyethyl)-4-methyl-γ-butyrolactone (8), dihydroaspyrone (10),
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Nine new C9 polyketides, named aspiketolactonol (1), aspilactonols A–F (27), aspyronol (9) and epiaspinonediol (11), were isolated together with five known polyketides, (S)-2-(2′-hydroxyethyl)-4-methyl-γ-butyrolactone (8), dihydroaspyrone (10), aspinotriol A (12), aspinotriol B (13) and chaetoquadrin F (14), from the secondary metabolites of an Aspergillus sp. 16-02-1 that was isolated from a deep-sea sediment sample. Structures of the new compounds, including their absolute configurations, were determined by spectroscopic methods, especially the 2D NMR, circular dichroism (CD), Mo2-induced CD and Mosher’s 1H NMR analyses. Compound 8 was isolated from natural sources for the first time, and the possible biosynthetic pathways for 114 were also proposed and discussed. Compounds 114 inhibited human cancer cell lines, K562, HL-60, HeLa and BGC-823, to varying extents. Full article
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Open AccessArticle Investigation of Indolglyoxamide and Indolacetamide Analogues of Polyamines as Antimalarial and Antitrypanosomal Agents
Mar. Drugs 2014, 12(6), 3138-3160; doi:10.3390/md12063138
Received: 10 April 2014 / Revised: 30 April 2014 / Accepted: 4 May 2014 / Published: 28 May 2014
Cited by 4 | PDF Full-text (795 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Pure compound screening has previously identified the indolglyoxy lamidospermidine ascidian metabolites didemnidine A and B (2 and 3) to be weak growth inhibitors of Trypanosoma brucei rhodesiense (IC50 59 and 44 μM, respectively) and Plasmodium falciparum (K1 dual drug resistant
[...] Read more.
Pure compound screening has previously identified the indolglyoxy lamidospermidine ascidian metabolites didemnidine A and B (2 and 3) to be weak growth inhibitors of Trypanosoma brucei rhodesiense (IC50 59 and 44 μM, respectively) and Plasmodium falciparum (K1 dual drug resistant strain) (IC50 41 and 15 μM, respectively), but lacking in selectivity (L6 rat myoblast, IC50 24 μM and 25 μM, respectively). To expand the structure–activity relationship of this compound class towards both parasites, we have prepared and biologically tested a library of analogues that includes indoleglyoxyl and indoleacetic “capping acids”, and polyamines including spermine (PA3-4-3) and extended analogues PA3-8-3 and PA3-12-3. 7-Methoxy substituted indoleglyoxylamides were typically found to exhibit the most potent antimalarial activity (IC50 10–92 nM) but with varying degrees of selectivity versus the L6 rat myoblast cell line. A 6-methoxyindolglyoxylamide analogue was the most potent growth inhibitor of T. brucei (IC50 0.18 μM) identified in the study: it, however, also exhibited poor selectivity (L6 IC50 6.0 μM). There was no apparent correlation between antimalarial and anti-T. brucei activity in the series. In vivo evaluation of one analogue against Plasmodium berghei was undertaken, demonstrating a modest 20.9% reduction in parasitaemia. Full article
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Open AccessArticle New Prenylxanthones from the Deep-Sea Derived Fungus Emericella sp. SCSIO 05240
Mar. Drugs 2014, 12(6), 3190-3202; doi:10.3390/md12063190
Received: 1 April 2014 / Revised: 3 May 2014 / Accepted: 5 May 2014 / Published: 28 May 2014
Cited by 8 | PDF Full-text (1153 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Four new prenylxanthones, emerixanthones A–D (14), together with six known analogues (510), were isolated from the culture of the deep-sea sediment derived fungus Emericella sp. SCSIO 05240, which was identified on the basis of morphology
[...] Read more.
Four new prenylxanthones, emerixanthones A–D (14), together with six known analogues (510), were isolated from the culture of the deep-sea sediment derived fungus Emericella sp. SCSIO 05240, which was identified on the basis of morphology and ITS sequence analysis. The newstructures were determined by NMR (1H, 13C NMR, HSQC, HMBC, and 1H-1H COSY), MS, CD, and optical rotation analysis. The absolute configuration of prenylxanthone skeleton was also confirmed by the X-ray crystallographic analysis. Compounds 1and 3 showed weak antibacterial activities, and 4 displayed mild antifungal activities against agricultural pathogens. Full article
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Open AccessArticle Zn-Driven Discovery of a Hydrothermal Vent Fungal Metabolite Clavatustide C, and an Experimental Study of the Anti-Cancer Mechanism of Clavatustide B
Mar. Drugs 2014, 12(6), 3203-3217; doi:10.3390/md12063203
Received: 15 February 2014 / Revised: 7 April 2014 / Accepted: 24 April 2014 / Published: 28 May 2014
Cited by 3 | PDF Full-text (1309 KB) | HTML Full-text | XML Full-text
Abstract
A naturally new cyclopeptide, clavatustide C, was produced as a stress metabolite in response to abiotic stress elicitation by one of the hydrothermal vent fluid components Zn in the cultured mycelia of Aspergillus clavatus C2WU, which were isolated from Xenograpsus testudinatus. X.
[...] Read more.
A naturally new cyclopeptide, clavatustide C, was produced as a stress metabolite in response to abiotic stress elicitation by one of the hydrothermal vent fluid components Zn in the cultured mycelia of Aspergillus clavatus C2WU, which were isolated from Xenograpsus testudinatus. X. testudinatus lives at extreme, toxic habitat around the sulphur-rich hydrothermal vents in Taiwan Kueishantao. The known compound clavatustide B was also isolated and purified. This is the first example of a new hydrothermal vent microbial secondary metabolite produced in response to abiotic Zn treatment. The structures were established by spectroscopic means. The regulation of G1-S transition in hepatocellular carcinoma cell lines by clavatustide B was observed in our previous study. The purpose of the present study was to verify these results in other types of cancer cell lines and elucidate the possible molecular mechanism for the anti-cancer activities of clavatustide B. In different human cancer cell lines, including pancreatic cancer (Panc-1), gastric cancer (MGC-803), colorectal cancer (SW-480), retinoblastoma (WERI-Rb-1) and prostate cancer (PC3), clavatustide B efficiently suppressed cell proliferations in a dose-dependent manner. Although different cancer cell lines presented variety in Max effect dose and IC50 dose, all cancer cell lines showed a lower Max effect dose and IC50 dose compared with human fibroblasts (hFB) (p < 0.05). Moreover, significant accumulations in G1 phases and a reduction in S phases (p < 0.05) were observed under clavatustide B treatment. The expression levels of 2622 genes including 39 cell cycle-associated genes in HepG2 cells were significantly altered by the treatment with 15 μg/mL clavatustide B after 48 h. CCNE2 (cyclin E2) was proved to be the key regulator of clavatustide B-induced G1-S transition blocking in several cancer cell lines by using real-time PCR. Full article
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Open AccessArticle Profiling of Polar Lipids in Marine Oleaginous Diatom Fistulifera solaris JPCC DA0580: Prediction of the Potential Mechanism for Eicosapentaenoic Acid-Incorporation into Triacylglycerol
Mar. Drugs 2014, 12(6), 3218-3230; doi:10.3390/md12063218
Received: 20 February 2014 / Revised: 22 April 2014 / Accepted: 23 April 2014 / Published: 28 May 2014
Cited by 7 | PDF Full-text (497 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The marine oleaginous diatom Fistulifera solaris JPCC DA0580 is a candidate for biodiesel production because of its high lipid productivity. However, the substantial eicosapentaenoic acid (EPA) content in this strain would affect the biodiesel quality. On the other hand, EPA is also known
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The marine oleaginous diatom Fistulifera solaris JPCC DA0580 is a candidate for biodiesel production because of its high lipid productivity. However, the substantial eicosapentaenoic acid (EPA) content in this strain would affect the biodiesel quality. On the other hand, EPA is also known as the essential health supplement for humans. EPAs are mainly incorporated into glycerolipids in the microalgal cell instead of the presence as free fatty acids. Therefore, the understanding of the EPA biosynthesis including the incorporation of the EPA into glycerolipids especially triacylglycerol (TAG) is fundamental for regulating EPA content for different purposes. In this study, in order to identify the biosynthesis pathway for the EPA-containing TAG species, a lipidomic characterization of the EPA-enriched polar lipids was performed by using direct infusion electrospray ionization (ESI)-Q-TRAP-MS and MS/MS analyses. The determination of the fatty acid positional distribution showed that the sn-2 position of all the chloroplast lipids and part of phosphatidylcholine (PC) species was occupied by C16 fatty acids. This result suggested the critical role of the chloroplast on the lipid synthesis in F. solaris. Furthermore, the exclusive presence of C18 fatty acids in PC highly indicated the biosynthesis of EPA on PC. Finally, the PC-based acyl-editing and head group exchange processes were proposed to be essential for the incorporation of EPA into TAG and chloroplast lipids. Full article
Open AccessArticle Ilimaquinone and Ethylsmenoquinone, Marine Sponge Metabolites, Suppress the Proliferation of Multiple Myeloma Cells by Down-Regulating the Level of β-Catenin
Mar. Drugs 2014, 12(6), 3231-3244; doi:10.3390/md12063231
Received: 11 December 2013 / Revised: 15 April 2014 / Accepted: 13 May 2014 / Published: 28 May 2014
Cited by 6 | PDF Full-text (764 KB) | HTML Full-text | XML Full-text
Abstract
Deregulation of Wnt/β-catenin signaling promotes the development of a broad range of human cancers, including multiple myeloma, and is thus a potential target for the development of therapeutics for this disease. Here, we used a cell-based reporter system to demonstrate that ilimaquinone and
[...] Read more.
Deregulation of Wnt/β-catenin signaling promotes the development of a broad range of human cancers, including multiple myeloma, and is thus a potential target for the development of therapeutics for this disease. Here, we used a cell-based reporter system to demonstrate that ilimaquinone and ethylsmenoquinone (formerly smenorthoquinone), sesquiterpene-quinones from a marine sponge, inhibited β-catenin response transcription induced with Wnt3a-conditioned medium, by down-regulating the level of intracellular β-catenin. Pharmacological inhibition of glycogen synthase kinase-3β did not abolish the ilimaquinone and ethylsmenoquinone-mediated β-catenin down-regulation. Degradation of β-catenin was consistently found in RPMI-8226 multiple myeloma cells after ilimaquinone and ethylsmenoquinone treatment. Ilimaquinone and ethylsmenoquinone repressed the expression of cyclin D1, c-myc, and axin-2, which are β-catenin/T-cell factor-dependent genes, and inhibited the proliferation of multiple myeloma cells. In addition, ilimaquinone and ethylsmenoquinone significantly induced G0/G1 cell cycle arrest and apoptosis in RPMI-8266 cells. These findings suggest that ilimaquinone and ethylsmenoquinone exert their anti-cancer activity by blocking the Wnt/β-catenin pathway and have significant potential as therapies for multiple myeloma. Full article
Open AccessArticle Violapyrones H and I, New Cytotoxic Compounds Isolated from Streptomyces sp. Associated with the Marine Starfish Acanthaster planci
Mar. Drugs 2014, 12(6), 3283-3291; doi:10.3390/md12063283
Received: 18 March 2014 / Revised: 8 May 2014 / Accepted: 16 May 2014 / Published: 30 May 2014
Cited by 10 | PDF Full-text (614 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two new α-pyrone derivatives, violapyrones H (1) and I (2), along with known violapyrones B (3) and C (4) were isolated from the fermentation broth of a marine actinomycete Streptomyces sp. The strain was derived
[...] Read more.
Two new α-pyrone derivatives, violapyrones H (1) and I (2), along with known violapyrones B (3) and C (4) were isolated from the fermentation broth of a marine actinomycete Streptomyces sp. The strain was derived from a crown-of-thorns starfish, Acanthaster planci, collected from Chuuk, Federated States of Micronesia. The structures of violapyrones were elucidated by the analysis of 1D and 2D NMR and HR-ESIMS data. Violapyrones (14) exhibited cytotoxicity against 10 human cancer cell lines with GI50 values of 1.10–26.12 μg/mL when tested using sulforhodamine B (SRB) assay. This is the first report on the cytotoxicity of violapyrones against cancer cell lines and the absolute configuration of violapyrone C. Full article
(This article belongs to the Special Issue Bioactive Compounds from Marine Microbes)
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Open AccessArticle The Protective Effect of Fucoidan in Rats with Streptozotocin-Induced Diabetic Nephropathy
Mar. Drugs 2014, 12(6), 3292-3306; doi:10.3390/md12063292
Received: 18 February 2014 / Revised: 9 May 2014 / Accepted: 9 May 2014 / Published: 30 May 2014
Cited by 12 | PDF Full-text (1555 KB) | HTML Full-text | XML Full-text
Abstract
Diabetic nephropathy (DN) has long been recognized as the leading cause of end-stage renal disease, but the efficacy of available strategies for the prevention of DN remains poor. The aim of this study was to investigate the possible beneficial effects of fucoidan (FPS)
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Diabetic nephropathy (DN) has long been recognized as the leading cause of end-stage renal disease, but the efficacy of available strategies for the prevention of DN remains poor. The aim of this study was to investigate the possible beneficial effects of fucoidan (FPS) in streptozotocin (STZ)-induced diabetes in rats. Wistar rats were made diabetic by injection of STZ after removal of the right kidney. FPS was administered to these diabetic rats for 10 weeks. Body weight, physical activity, renal function, and renal morphometry were measured after 10 weeks of treatment. In the FPS-treated group, the levels of blood glucose, BUN, Ccr and Ucr decreased significantly, and microalbumin, serum insulin and the β2-MG content increased significantly. Moreover, the FPS-treated group showed improvements in renal morphometry. In summary, FPS can ameliorate the metabolic abnormalities of diabetic rats and delay the progression of diabetic renal complications. Full article
Open AccessArticle Identification of Marine Neuroactive Molecules in Behaviour-Based Screens in the Larval Zebrafish
Mar. Drugs 2014, 12(6), 3307-3322; doi:10.3390/md12063307
Received: 30 January 2014 / Revised: 19 May 2014 / Accepted: 19 May 2014 / Published: 30 May 2014
Cited by 3 | PDF Full-text (1485 KB) | HTML Full-text | XML Full-text
Abstract
High-throughput behavior-based screen in zebrafish is a powerful approach for the discovery of novel neuroactive small molecules for treatment of nervous system diseases such as epilepsy. To identify neuroactive small molecules, we first screened 36 compounds (136) derived from
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High-throughput behavior-based screen in zebrafish is a powerful approach for the discovery of novel neuroactive small molecules for treatment of nervous system diseases such as epilepsy. To identify neuroactive small molecules, we first screened 36 compounds (136) derived from marine natural products xyloketals and marine isoprenyl phenyl ether obtained from the mangrove fungus. Compound 1 demonstrated the most potent inhibition on the locomotor activity in larval zebrafish. Compounds 3742 were further synthesized and their potential anti-epilepsy action was then examined in a PTZ-induced epilepsy model in zebrafish. Compound 1 and compounds 39, 40 and 41 could significantly attenuate PTZ-induced locomotor hyperactivity and elevation of c-fos mRNA in larval zebrafish. Compound 40 showed the most potent inhibitory action against PTZ-induced hyperactivity. The structure-activity analysis showed that the OH group at 12-position played a critical role and the substituents at the 13-position were well tolerated in the inhibitory activity of xyloketal derivatives. Thus, these derivatives may provide some novel drug candidates for the treatment of epilepsy. Full article
Open AccessArticle Metabolomic Profiling and Genomic Study of a Marine Sponge-Associated Streptomyces sp.
Mar. Drugs 2014, 12(6), 3323-3351; doi:10.3390/md12063323
Received: 25 March 2014 / Revised: 7 May 2014 / Accepted: 21 May 2014 / Published: 2 June 2014
Cited by 13 | PDF Full-text (831 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Metabolomics and genomics are two complementary platforms for analyzing an organism as they provide information on the phenotype and genotype, respectively. These two techniques were applied in the dereplication and identification of bioactive compounds from a Streptomyces sp. (SM8) isolated from the sponge
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Metabolomics and genomics are two complementary platforms for analyzing an organism as they provide information on the phenotype and genotype, respectively. These two techniques were applied in the dereplication and identification of bioactive compounds from a Streptomyces sp. (SM8) isolated from the sponge Haliclona simulans from Irish waters. Streptomyces strain SM8 extracts showed antibacterial and antifungal activity. NMR analysis of the active fractions proved that hydroxylated saturated fatty acids were the major components present in the antibacterial fractions. Antimycin compounds were initially putatively identified in the antifungal fractions using LC-Orbitrap. Their presence was later confirmed by comparison to a standard. Genomic analysis of Streptomyces sp. SM8 revealed the presence of multiple secondary metabolism gene clusters, including a gene cluster for the biosynthesis of the antifungal antimycin family of compounds. The antimycin gene cluster of Streptomyces sp. SM8 was inactivated by disruption of the antimycin biosynthesis gene antC. Extracts from this mutant strain showed loss of antimycin production and significantly less antifungal activity than the wild-type strain. Three butenolides, 4,10-dihydroxy-10-methyl-dodec-2-en-1,4-olide (1), 4,11-dihydroxy-10-methyl-dodec-2-en-1,4-olide (2), and 4-hydroxy-10-methyl-11-oxo-dodec-2-en-1,4-olide (3) that had previously been reported from marine Streptomyces species were also isolated from SM8. Comparison of the extracts of Streptomyces strain SM8 and its host sponge, H. simulans, using LC-Orbitrap revealed the presence of metabolites common to both extracts, providing direct evidence linking sponge metabolites to a specific microbial symbiont. Full article
(This article belongs to the Special Issue Metabolomics - Applications in Marine Natural Products Chemistry)
Open AccessArticle First Total Syntheses and Antimicrobial Evaluation of Penicimonoterpene, a Marine-Derived Monoterpenoid, and Its Various Derivatives
Mar. Drugs 2014, 12(6), 3352-3370; doi:10.3390/md12063352
Received: 28 February 2014 / Revised: 8 April 2014 / Accepted: 10 April 2014 / Published: 3 June 2014
Cited by 2 | PDF Full-text (791 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The first total synthesis of marine-derived penicimonoterpene (±)-1 has been achieved in four steps from 6-methylhept-5-en-2-one using a Reformatsky reaction as the key step to construct the basic carbon skeleton. A total of 24 new derivatives of 1 have also been designed
[...] Read more.
The first total synthesis of marine-derived penicimonoterpene (±)-1 has been achieved in four steps from 6-methylhept-5-en-2-one using a Reformatsky reaction as the key step to construct the basic carbon skeleton. A total of 24 new derivatives of 1 have also been designed and synthesized. Their structures were characterized by analysis of their 1H NMR, 13C NMR and HRESIMS data. Some of them showed significant antibacterial activity against Aeromonas hydrophila, Escherichia coli, Micrococcus luteus, Staphylococcus aureus, Vibrio anguillarum, V. harveyi and/or V. parahaemolyticus, and some showed activity against plant-pathogenic fungi (Alternaria brassicae, Colletotrichum gloeosporioides and/or Fusarium graminearum). Some of the derivatives exhibited antimicrobial MIC values ranging from 0.25 to 4 μg/mL, which were stronger than those of the positive control. Notably, Compounds 3b and 10 showed extremely high selectively against plant-pathogenic fungus F. graminearum (MIC 0.25 μg/mL) and pathogenic bacteria E. coli (MIC 1 μg/mL), implying their potential as antimicrobial agents. SAR analysis of 1 and its derivatives indicated that modification of the carbon-carbon double bond at C-6/7, of groups on the allylic methylene unit and of the carbonyl group at C-1, effectively enhanced the antimicrobial activity. Full article
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Open AccessArticle Numerosol A–D, New Cembranoid Diterpenes from the Soft Coral Sinularia numerosa
Mar. Drugs 2014, 12(6), 3371-3380; doi:10.3390/md12063371
Received: 4 March 2014 / Revised: 14 April 2014 / Accepted: 15 April 2014 / Published: 3 June 2014
Cited by 3 | PDF Full-text (798 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Four new cembrane-type diterpenes; numerosol A–D (14); along with a known steroid; gibberoketosterol (5); were isolated from the Taiwanese soft coral Sinularia numerosa. The structures of these metabolites were determined by extensive analysis of spectroscopic data.
[...] Read more.
Four new cembrane-type diterpenes; numerosol A–D (14); along with a known steroid; gibberoketosterol (5); were isolated from the Taiwanese soft coral Sinularia numerosa. The structures of these metabolites were determined by extensive analysis of spectroscopic data. Gibberoketosterol (5) exhibited cytotoxicity against P-388 (mouse lymphocytic leukemia) cell line with an ED50 of 6.9 μM. Full article
Open AccessArticle Effects of Long Chain Fatty Acid Synthesis and Associated Gene Expression in Microalga Tetraselmis sp.
Mar. Drugs 2014, 12(6), 3381-3398; doi:10.3390/md12063381
Received: 10 April 2014 / Revised: 9 May 2014 / Accepted: 15 May 2014 / Published: 4 June 2014
Cited by 7 | PDF Full-text (1247 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
With the depletion of global fish stocks, caused by high demand and effective fishing techniques, alternative sources for long chain omega-3 fatty acids are required for human nutrition and aquaculture feeds. Recent research has focused on land-based cultivation of microalgae, the primary producers
[...] Read more.
With the depletion of global fish stocks, caused by high demand and effective fishing techniques, alternative sources for long chain omega-3 fatty acids are required for human nutrition and aquaculture feeds. Recent research has focused on land-based cultivation of microalgae, the primary producers of omega-3 fatty acids in the marine food web. The effect of salinity on fatty acids and related gene expression was studied in the model marine microalga, Tetraselmis sp. M8. Correlations were found for specific fatty acid biosynthesis and gene expression according to salinity and the growth phase. Low salinity was found to increase the conversion of C18:4 stearidonic acid (SDA) to C20:4 eicosatetraenoic acid (ETA), correlating with increased transcript abundance of the Δ-6-elongase-encoding gene in salinities of 5 and 10 ppt compared to higher salinity levels. The expression of the gene encoding β-ketoacyl-coenzyme was also found to increase at lower salinities during the nutrient deprivation phase (Day 4), but decreased with further nutrient stress. Nutrient deprivation also triggered fatty acids synthesis at all salinities, and C20:5 eicosapentaenoic acid (EPA) increased relative to total fatty acids, with nutrient starvation achieving a maximum of 7% EPA at Day 6 at a salinity of 40 ppt. Full article
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Open AccessArticle Potent Cytotoxic Peptides from the Australian Marine Sponge Pipestela candelabra
Mar. Drugs 2014, 12(6), 3399-3415; doi:10.3390/md12063399
Received: 4 March 2014 / Revised: 10 April 2014 / Accepted: 14 April 2014 / Published: 4 June 2014
Cited by 3 | PDF Full-text (893 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two consecutive prefractionated fractions of the Australian marine sponge extract, Pipestela candelabra, were identified to be selectively active on the human prostate cancer cells (PC3) compared to the human neonatal foreskin fibroblast non-cancer cells (NFF). Twelve secondary metabolites were isolated in which
[...] Read more.
Two consecutive prefractionated fractions of the Australian marine sponge extract, Pipestela candelabra, were identified to be selectively active on the human prostate cancer cells (PC3) compared to the human neonatal foreskin fibroblast non-cancer cells (NFF). Twelve secondary metabolites were isolated in which four compounds are new small peptides. Their structures were characterized by spectroscopic and chemical analysis. These compounds inhibited selectively the growth of prostate cancer cells with IC50 values in the picomolar to sub-micromolar range. Structure-activity relationship of these compounds is discussed. Full article
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Open AccessArticle Metabolomic Tools for Secondary Metabolite Discovery from Marine Microbial Symbionts
Mar. Drugs 2014, 12(6), 3416-3448; doi:10.3390/md12063416
Received: 6 March 2014 / Revised: 20 May 2014 / Accepted: 20 May 2014 / Published: 5 June 2014
Cited by 11 | PDF Full-text (1484 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Marine invertebrate-associated symbiotic bacteria produce a plethora of novel secondary metabolites which may be structurally unique with interesting pharmacological properties. Selection of strains usually relies on literature searching, genetic screening and bioactivity results, often without considering the chemical novelty and abundance of secondary
[...] Read more.
Marine invertebrate-associated symbiotic bacteria produce a plethora of novel secondary metabolites which may be structurally unique with interesting pharmacological properties. Selection of strains usually relies on literature searching, genetic screening and bioactivity results, often without considering the chemical novelty and abundance of secondary metabolites being produced by the microorganism until the time-consuming bioassay-guided isolation stages. To fast track the selection process, metabolomic tools were used to aid strain selection by investigating differences in the chemical profiles of 77 bacterial extracts isolated from cold water marine invertebrates from Orkney, Scotland using liquid chromatography-high resolution mass spectrometry (LC-HRMS) and nuclear magnetic resonance (NMR) spectroscopy. Following mass spectrometric analysis and dereplication using an Excel macro developed in-house, principal component analysis (PCA) was employed to differentiate the bacterial strains based on their chemical profiles. NMR 1H and correlation spectroscopy (COSY) were also employed to obtain a chemical fingerprint of each bacterial strain and to confirm the presence of functional groups and spin systems. These results were then combined with taxonomic identification and bioassay screening data to identify three bacterial strains, namely Bacillus sp. 4117, Rhodococcus sp. ZS402 and Vibrio splendidus strain LGP32, to prioritize for scale-up based on their chemically interesting secondary metabolomes, established through dereplication and interesting bioactivities, determined from bioassay screening. Full article
(This article belongs to the Special Issue Metabolomics - Applications in Marine Natural Products Chemistry)
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Open AccessArticle Characterization of a Novel Conus bandanus Conopeptide Belonging to the M-Superfamily Containing Bromotryptophan
Mar. Drugs 2014, 12(6), 3449-3465; doi:10.3390/md12063449
Received: 21 February 2014 / Revised: 7 March 2014 / Accepted: 22 May 2014 / Published: 5 June 2014
Cited by 3 | PDF Full-text (2064 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A novel conotoxin (conopeptide) was biochemically characterized from the crude venom of the molluscivorous marine snail, Conus bandanus (Hwass in Bruguière, 1792), collected in the south-central coast of Vietnam. The peptide was identified by screening bromotryptophan from chromatographic fractions of the crude venom.
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A novel conotoxin (conopeptide) was biochemically characterized from the crude venom of the molluscivorous marine snail, Conus bandanus (Hwass in Bruguière, 1792), collected in the south-central coast of Vietnam. The peptide was identified by screening bromotryptophan from chromatographic fractions of the crude venom. Tandem mass spectrometry techniques were used to detect and localize different post-translational modifications (PTMs) present in the BnIIID conopeptide. The sequence was confirmed by Edman’s degradation and mass spectrometry revealing that the purified BnIIID conopeptide had 15 amino acid residues, with six cysteines at positions 1, 2, 7, 11, 13, and 14, and three PTMs: bromotryptophan, γ-carboxy glutamate, and amidated aspartic acid, at positions “4”, “5”, and “15”, respectively. The BnIIID peptide was synthesized for comparison with the native peptide. Homology comparison with conopeptides having the III-cysteine framework (–CCx1x2x3x4Cx1x2x3Cx1CC–) revealed that BnIIID belongs to the M-1 family of conotoxins. This is the first report of a member of the M-superfamily containing bromotryptophan as PTM. Full article
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Open AccessArticle Chromomycins A2 and A3 from Marine Actinomycetes with TRAIL Resistance-Overcoming and Wnt Signal Inhibitory Activities
Mar. Drugs 2014, 12(6), 3466-3476; doi:10.3390/md12063466
Received: 12 March 2014 / Revised: 5 April 2014 / Accepted: 9 April 2014 / Published: 5 June 2014
Cited by 7 | PDF Full-text (430 KB) | HTML Full-text | XML Full-text
Abstract
A biological screening study of an actinomycetes strain assembly was conducted using a cell-based cytotoxicity assay. The CKK1019 strain was isolated from a sea sand sample. Cytotoxicity-guided fractionation of the CKK1019 strain culture broth, which exhibited cytotoxicity, led to the isolation of chromomycins
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A biological screening study of an actinomycetes strain assembly was conducted using a cell-based cytotoxicity assay. The CKK1019 strain was isolated from a sea sand sample. Cytotoxicity-guided fractionation of the CKK1019 strain culture broth, which exhibited cytotoxicity, led to the isolation of chromomycins A2 (1) and A3 (2). 1 and 2 showed potent cytotoxicity against the human gastric adenocarcinoma (AGS) cell line (IC50 1; 1.7 and 2; 22.1 nM), as well as strong inhibitory effects against TCF/β-catenin transcription (IC50 1; 1.8 and 2; 15.9 nM). 2 showed the ability to overcome tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) resistance. To the best of our knowledge, the effects of chromomycins A2 (1) and A3 (2) on TRAIL resistance-overcoming activity, and on the Wnt signaling pathway, have not been reported previously. Thus, 1 and 2 warrant potential drug lead studies in relation to TRAIL-resistant and Wnt signal-related diseases and offer potentially useful chemical probes for investigating TRAIL resistance and the Wnt signaling pathway. Full article
Open AccessCommunication Cespitulones A and B, Cytotoxic Diterpenoids of a New Structure Class from the Soft Coral Cespitularia taeniata
Mar. Drugs 2014, 12(6), 3477-3486; doi:10.3390/md12063477
Received: 2 April 2014 / Revised: 9 May 2014 / Accepted: 12 May 2014 / Published: 5 June 2014
Cited by 2 | PDF Full-text (807 KB) | HTML Full-text | XML Full-text
Abstract
Two novel diterpenoids, cespitulones A (1) and B (2), were isolated from extracts of the soft coral Cespitularia taeniata. Both compounds possess an unprecedented bicyclo [10.3.1] ring system with C-C bond connections between C-10 and C-20, and between
[...] Read more.
Two novel diterpenoids, cespitulones A (1) and B (2), were isolated from extracts of the soft coral Cespitularia taeniata. Both compounds possess an unprecedented bicyclo [10.3.1] ring system with C-C bond connections between C-10 and C-20, and between C-20 and C-11. Their structures were elucidated on the basis of extensive spectroscopic analyses. Compound 1 exhibited significant cytotoxicity against human medulloblastoma and colon adenocarcinoma cancer cells. Full article
Open AccessArticle Acetylcholinesterase Inhibitory Activity of Pigment Echinochrome A from Sea Urchin Scaphechinus mirabilis
Mar. Drugs 2014, 12(6), 3560-3573; doi:10.3390/md12063560
Received: 24 March 2014 / Revised: 10 May 2014 / Accepted: 29 May 2014 / Published: 10 June 2014
Cited by 9 | PDF Full-text (561 KB) | HTML Full-text | XML Full-text
Abstract
Echinochrome A (EchA) is a dark-red pigment of the polyhydroxynaphthoquinone class isolated from sea urchin Scaphechinus mirabilis. Acetylcholinesterase (AChE) inhibitors are used in the treatment of various neuromuscular disorders, and are considered as strong therapeutic agents for the treatment of Alzheimer’s disease
[...] Read more.
Echinochrome A (EchA) is a dark-red pigment of the polyhydroxynaphthoquinone class isolated from sea urchin Scaphechinus mirabilis. Acetylcholinesterase (AChE) inhibitors are used in the treatment of various neuromuscular disorders, and are considered as strong therapeutic agents for the treatment of Alzheimer’s disease (AD). Although EchA is clinically used to treat ophthalmic diseases and limit infarct formation during ischemia/ reperfusion injury, anti-AChE effect of EchA is still unknown. In this study, we investigated the anti-AChE effect of EchA in vitro. EchA and its exhausted form which lost anti-oxidant capacity did not show any significant cytotoxicy on the H9c2 and A7r5 cells. EchA inhibited AChE with an irreversible and uncompetitive mode. In addition, EchA showed reactive oxygen species scavenging activity, particularly with nitric oxide. These findings indicate new therapeutic potential for EchA in treating reduced acetylcholine-related diseases including AD and provide an insight into developing new AChE inhibitors. Full article
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Open AccessArticle Diazaquinomycins E–G, Novel Diaza-Anthracene Analogs from a Marine-Derived Streptomyces sp.
Mar. Drugs 2014, 12(6), 3574-3586; doi:10.3390/md12063574
Received: 12 May 2014 / Revised: 25 May 2014 / Accepted: 28 May 2014 / Published: 11 June 2014
Cited by 4 | PDF Full-text (856 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
As part of our program to identify novel secondary metabolites that target drug-resistant ovarian cancers, a screening of our aquatic-derived actinomycete fraction library against a cisplatin-resistant ovarian cancer cell line (OVCAR5) led to the isolation of novel diaza-anthracene antibiotic diazaquinomycin E (DAQE; 1
[...] Read more.
As part of our program to identify novel secondary metabolites that target drug-resistant ovarian cancers, a screening of our aquatic-derived actinomycete fraction library against a cisplatin-resistant ovarian cancer cell line (OVCAR5) led to the isolation of novel diaza-anthracene antibiotic diazaquinomycin E (DAQE; 1), the isomeric mixture of diazaquinomycin F (DAQF; 2) and diazaquinomycin G (DAQG; 3), and known analog diazaquinomycin A (DAQA; 4). The structures of DAQF and DAQG were solved through deconvolution of X-Ray diffraction data of their corresponding co-crystal. DAQE and DAQA exhibited moderate LC50 values against OVCAR5 of 9.0 and 8.8 μM, respectively. At lethal concentrations of DAQA, evidence of DNA damage was observed via induction of apoptosis through cleaved-PARP. Herein, we will discuss the isolation, structure elucidation, and biological activity of these secondary metabolites. Full article
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Open AccessArticle Link between Domoic Acid Production and Cell Physiology after Exchange of Bacterial Communities between Toxic Pseudo-nitzschia multiseries and Non-Toxic Pseudo-nitzschia delicatissima
Mar. Drugs 2014, 12(6), 3587-3607; doi:10.3390/md12063587
Received: 5 March 2014 / Revised: 4 April 2014 / Accepted: 17 April 2014 / Published: 11 June 2014
Cited by 3 | PDF Full-text (660 KB) | HTML Full-text | XML Full-text
Abstract
Bacteria are known to influence domoic acid (DA) production by Pseudo-nitzschia spp., but the link between DA production and physiology of diatoms requires more investigation. We compared a toxic P. multiseries to a non-toxic P. delicatissima, investigating links between DA production, physiological
[...] Read more.
Bacteria are known to influence domoic acid (DA) production by Pseudo-nitzschia spp., but the link between DA production and physiology of diatoms requires more investigation. We compared a toxic P. multiseries to a non-toxic P. delicatissima, investigating links between DA production, physiological parameters, and co-occurring bacteria. Bacterial communities in cultures of both species were reduced by antibiotic treatment, and each of the diatoms was inoculated with the bacterial community of the other species. The physiology of P. delicatissima was minimally affected by the absence of bacteria or the presence of alien bacteria, and no DA was detected. P. multiseries grew faster without bacteria, did not produce a significant amount of DA, and exhibited physiological characteristics of healthy cells. When grown with alien bacteria, P. multiseries did not grow and produced more DA; the physiology of these cells was affected, with decreases in chlorophyll content and photosynthetic efficiency, an increase in esterase activity, and almost 50% mortality of the cells. The alien bacterial community had morphological and cellular characteristics very different from the original bacteria, and the number of free-living bacteria per algal cell was much higher, suggesting the involvement of bacteria in DA production. Full article
(This article belongs to the Special Issue Metabolites in Diatoms)
Open AccessArticle Eurothiocin A and B, Sulfur-Containing Benzofurans from a Soft Coral-Derived Fungus Eurotium rubrum SH-823
Mar. Drugs 2014, 12(6), 3669-3680; doi:10.3390/md12063669
Received: 30 April 2014 / Revised: 3 June 2014 / Accepted: 13 June 2014 / Published: 20 June 2014
Cited by 13 | PDF Full-text (864 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two new sulfur-containing benzofuran derivatives, eurothiocin A and B (1 and 2), along with five known compounds, zinniol (3), butyrolactone I (4), aspernolide D (5), vermistatin (6), and methoxyvermistatin (7), were
[...] Read more.
Two new sulfur-containing benzofuran derivatives, eurothiocin A and B (1 and 2), along with five known compounds, zinniol (3), butyrolactone I (4), aspernolide D (5), vermistatin (6), and methoxyvermistatin (7), were isolated from the cultures of Eurotium rubrum SH-823, a fungus obtained from a Sarcophyton sp. soft coral collected from the South China Sea. The new compounds (1 and 2) share a methyl thiolester moiety, which is quite rare among natural secondary metabolites. The structures of these metabolites were assigned on the basis of detailed spectroscopic analysis. The absolute configurations of 1 and 2 were determined by comparison of the experimental and calculated electronic circular dichroism (ECD) data. Compounds 1 and 2 exhibited more potent inhibitory effects against α-glucosidase activity than the clinical α-glucosidase inhibitor acarbose. Further mechanistic analysis showed that both of them exhibited competitive inhibition characteristics. Full article
(This article belongs to the Special Issue Bioactive Compounds from Marine Microbes)
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Open AccessArticle Accurate Dereplication of Bioactive Secondary Metabolites from Marine-Derived Fungi by UHPLC-DAD-QTOFMS and a MS/HRMS Library
Mar. Drugs 2014, 12(6), 3681-3705; doi:10.3390/md12063681
Received: 28 February 2014 / Revised: 23 May 2014 / Accepted: 11 June 2014 / Published: 20 June 2014
Cited by 28 | PDF Full-text (693 KB) | HTML Full-text | XML Full-text
Abstract
In drug discovery, reliable and fast dereplication of known compounds is essential for identification of novel bioactive compounds. Here, we show an integrated approach using ultra-high performance liquid chromatography-diode array detection-quadrupole time of flight mass spectrometry (UHPLC-DAD-QTOFMS) providing both accurate mass full-scan mass
[...] Read more.
In drug discovery, reliable and fast dereplication of known compounds is essential for identification of novel bioactive compounds. Here, we show an integrated approach using ultra-high performance liquid chromatography-diode array detection-quadrupole time of flight mass spectrometry (UHPLC-DAD-QTOFMS) providing both accurate mass full-scan mass spectrometry (MS) and tandem high resolution MS (MS/HRMS) data. The methodology was demonstrated on compounds from bioactive marine-derived strains of Aspergillus, Penicillium, and Emericellopsis, including small polyketides, non-ribosomal peptides, terpenes, and meroterpenoids. The MS/HRMS data were then searched against an in-house MS/HRMS library of ~1300 compounds for unambiguous identification. The full scan MS data was used for dereplication of compounds not in the MS/HRMS library, combined with ultraviolet/visual (UV/Vis) and MS/HRMS data for faster exclusion of database search results. This led to the identification of four novel isomers of the known anticancer compound, asperphenamate. Except for very low intensity peaks, no false negatives were found using the MS/HRMS approach, which proved to be robust against poor data quality caused by system overload or loss of lock-mass. Only for small polyketides, like patulin, were both retention time and UV/Vis spectra necessary for unambiguous identification. For the ophiobolin family with many structurally similar analogues partly co-eluting, the peaks could be assigned correctly by combining MS/HRMS data and m/z of the [M + Na]+ ions. Full article
(This article belongs to the Special Issue Metabolomics - Applications in Marine Natural Products Chemistry)
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Open AccessArticle Confirmation of Pinnatoxins and Spirolides in Shellfish and Passive Samplers from Catalonia (Spain) by Liquid Chromatography Coupled with Triple Quadrupole and High-Resolution Hybrid Tandem Mass Spectrometry
Mar. Drugs 2014, 12(6), 3706-3732; doi:10.3390/md12063706
Received: 4 April 2014 / Revised: 13 May 2014 / Accepted: 19 May 2014 / Published: 23 June 2014
Cited by 10 | PDF Full-text (1011 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Cyclic imines are lipophilic marine toxins that bioaccumulate in seafood. Their structure comprises a cyclic-imino moiety, responsible for acute neurotoxicity in mice. Cyclic imines have not been linked yet to human poisonings and are not regulated in Europe, although the European Food Safety
[...] Read more.
Cyclic imines are lipophilic marine toxins that bioaccumulate in seafood. Their structure comprises a cyclic-imino moiety, responsible for acute neurotoxicity in mice. Cyclic imines have not been linked yet to human poisonings and are not regulated in Europe, although the European Food Safety Authority requires more data to perform a conclusive risk assessment for consumers. This work presents the first detection of pinnatoxin G (PnTX-G) in Spain and 13-desmethyl spirolide C (SPX-1) in shellfish from Catalonia (Spain, NW Mediterranean Sea). Cyclic imines were found at low concentrations (2 to 60 µg/kg) in 13 samples of mussels and oysters (22 samples analyzed). Pinnatoxin G has been also detected in 17 seawater samples (out of 34) using solid phase adsorption toxin tracking devices (0.3 to 0.9 µg/kg-resin). Pinnatoxin G and SPX-1 were confirmed with both low and high resolution (<2 ppm) mass spectrometry by comparison of the response with that from reference standards. For other analogs without reference standards, we applied a strategy combining low resolution MS with a triple quadrupole mass analyzer for a fast and reliable screening, and high resolution MS LTQ Orbitrap® for unambiguous confirmation. The advantages and limitations of using high resolution MS without reference standards were discussed. Full article
(This article belongs to the Special Issue Emerging Marine Toxins)
Open AccessArticle Analysis of the Biomass Composition of the Demosponge Amphimedon queenslandica on Heron Island Reef, Australia
Mar. Drugs 2014, 12(6), 3733-3753; doi:10.3390/md12063733
Received: 28 March 2014 / Revised: 20 May 2014 / Accepted: 29 May 2014 / Published: 23 June 2014
Cited by 1 | PDF Full-text (736 KB) | HTML Full-text | XML Full-text
Abstract
Marine sponges are a potential source of important pharmaceutical drugs, the commercialisation of which is restricted by the difficulties of obtaining a sufficient and regular supply of biomass. One way to optimize commercial cell lines for production is the in-depth characterization and target
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Marine sponges are a potential source of important pharmaceutical drugs, the commercialisation of which is restricted by the difficulties of obtaining a sufficient and regular supply of biomass. One way to optimize commercial cell lines for production is the in-depth characterization and target identification through genome scale metabolic modeling and flux analysis. By applying these tools to a sponge, we hope to gain insights into how biomass is formed. We chose Amphimedon queenslandica as it has an assembled and annotated genome, a prerequisite for genome scale modeling. The first stepping stone on the way to metabolic flux analysis in a sponge holobiont, is the characterization of its biomass composition. In this study we quantified the macromolecular composition and investigated the variation between and within sponges of a single population. We found lipids and protein to be the most abundant macromolecules, while carbohydrates were the most variable. We also analysed the composition and abundance of the fatty acids and amino acids, the important building blocks required to synthesise the abundant macromolecule types, lipids, and protein. These data complement the extensive genomic information available for A. queenslandica and lay the basis for genome scale modelling and flux analysis. Full article
Open AccessArticle Amino Alcohols from the Ascidian Pseudodistoma sp.
Mar. Drugs 2014, 12(6), 3754-3769; doi:10.3390/md12063754
Received: 9 May 2014 / Revised: 30 May 2014 / Accepted: 30 May 2014 / Published: 24 June 2014
Cited by 4 | PDF Full-text (696 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Seven new amino alcohol compounds, pseudoaminols A–G (17), were isolated from the ascidian Pseudodistoma sp. collected off the coast of Chuja-do, Korea. Structures of these new compounds were determined by analysis of the spectroscopic data and from chemical conversion.
[...] Read more.
Seven new amino alcohol compounds, pseudoaminols A–G (17), were isolated from the ascidian Pseudodistoma sp. collected off the coast of Chuja-do, Korea. Structures of these new compounds were determined by analysis of the spectroscopic data and from chemical conversion. The presence of an N-carboxymethyl group in two of the new compounds (6 and 7) is unprecedented among amino alcohols. Several of these compounds exhibited moderate antimicrobial activity and cytotoxicity, as well as weak inhibitory activity toward Na+/K+-ATPase. Full article
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Open AccessArticle Defensive Metabolites from Antarctic Invertebrates: Does Energetic Content Interfere with Feeding Repellence?
Mar. Drugs 2014, 12(6), 3770-3791; doi:10.3390/md12063770
Received: 1 April 2014 / Revised: 23 May 2014 / Accepted: 29 May 2014 / Published: 24 June 2014
Cited by 4 | PDF Full-text (789 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Many bioactive products from benthic invertebrates mediating ecological interactions have proved to reduce predation, but their mechanisms of action, and their molecular identities, are usually unknown. It was suggested, yet scarcely investigated, that nutritional quality interferes with defensive metabolites. This means that antifeedants
[...] Read more.
Many bioactive products from benthic invertebrates mediating ecological interactions have proved to reduce predation, but their mechanisms of action, and their molecular identities, are usually unknown. It was suggested, yet scarcely investigated, that nutritional quality interferes with defensive metabolites. This means that antifeedants would be less effective when combined with energetically rich prey, and that higher amounts of defensive compounds would be needed for predator avoidance. We evaluated the effects of five types of repellents obtained from Antarctic invertebrates, in combination with diets of different energetic values. The compounds came from soft corals, ascidians and hexactinellid sponges; they included wax esters, alkaloids, a meroterpenoid, a steroid, and the recently described organic acid, glassponsine. Feeding repellency was tested through preference assays by preparing diets (alginate pearls) combining different energetic content and inorganic material. Experimental diets contained various concentrations of each repellent product, and were offered along with control compound-free pearls, to the Antarctic omnivore amphipod Cheirimedon femoratus. Meridianin alkaloids were the most active repellents, and wax esters were the least active when combined with foods of distinct energetic content. Our data show that levels of repellency vary for each compound, and that they perform differently when mixed with distinct assay foods. The natural products that interacted the most with energetic content were those occurring in nature at higher concentrations. The bioactivity of the remaining metabolites tested was found to depend on a threshold concentration, enough to elicit feeding repellence, independently from nutritional quality. Full article
(This article belongs to the collection Bioactive Compounds from Marine Invertebrates)
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Review

Jump to: Research

Open AccessReview Marennine, Promising Blue Pigments from a Widespread Haslea Diatom Species Complex
Mar. Drugs 2014, 12(6), 3161-3189; doi:10.3390/md12063161
Received: 19 March 2014 / Revised: 29 April 2014 / Accepted: 29 April 2014 / Published: 28 May 2014
Cited by 6 | PDF Full-text (3074 KB) | HTML Full-text | XML Full-text
Abstract
In diatoms, the main photosynthetic pigments are chlorophylls a and c, fucoxanthin, diadinoxanthin and diatoxanthin. The marine pennate diatom Haslea ostrearia has long been known for producing, in addition to these generic pigments, a water-soluble blue pigment, marennine. This pigment, responsible for
[...] Read more.
In diatoms, the main photosynthetic pigments are chlorophylls a and c, fucoxanthin, diadinoxanthin and diatoxanthin. The marine pennate diatom Haslea ostrearia has long been known for producing, in addition to these generic pigments, a water-soluble blue pigment, marennine. This pigment, responsible for the greening of oysters in western France, presents different biological activities: allelopathic, antioxidant, antibacterial, antiviral, and growth-inhibiting. A method to extract and purify marennine has been developed, but its chemical structure could hitherto not be resolved. For decades, H. ostrearia was the only organism known to produce marennine, and can be found worldwide. Our knowledge about H. ostrearia-like diatom biodiversity has recently been extended with the discovery of several new species of blue diatoms, the recently described H. karadagensis, H. silbo sp. inedit. and H. provincialis sp. inedit. These blue diatoms produce different marennine-like pigments, which belong to the same chemical family and present similar biological activities. Aside from being a potential source of natural blue pigments, H. ostrearia-like diatoms thus present a commercial potential for aquaculture, cosmetics, food and health industries. Full article
(This article belongs to the Special Issue Metabolites in Diatoms)
Open AccessReview Quorum Quenching Agents: Resources for Antivirulence Therapy
Mar. Drugs 2014, 12(6), 3245-3282; doi:10.3390/md12063245
Received: 29 January 2014 / Revised: 7 May 2014 / Accepted: 9 May 2014 / Published: 30 May 2014
Cited by 10 | PDF Full-text (1790 KB) | HTML Full-text | XML Full-text
Abstract
The continuing emergence of antibiotic-resistant pathogens is a concern to human health and highlights the urgent need for the development of alternative therapeutic strategies. Quorum sensing (QS) regulates virulence in many bacterial pathogens, and thus, is a promising target for antivirulence therapy which
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The continuing emergence of antibiotic-resistant pathogens is a concern to human health and highlights the urgent need for the development of alternative therapeutic strategies. Quorum sensing (QS) regulates virulence in many bacterial pathogens, and thus, is a promising target for antivirulence therapy which may inhibit virulence instead of cell growth and division. This means that there is little selective pressure for the evolution of resistance. Many natural quorum quenching (QQ) agents have been identified. Moreover, it has been shown that many microorganisms are capable of producing small molecular QS inhibitors and/or macromolecular QQ enzymes, which could be regarded as a strategy for bacteria to gain benefits in competitive environments. More than 30 species of marine QQ bacteria have been identified thus far, but only a few of them have been intensively studied. Recent studies indicate that an enormous number of QQ microorganisms are undiscovered in the highly diverse marine environments, and these marine microorganism-derived QQ agents may be valuable resources for antivirulence therapy. Full article
Open AccessReview Chlorella zofingiensis as an Alternative Microalgal Producer of Astaxanthin: Biology and Industrial Potential
Mar. Drugs 2014, 12(6), 3487-3515; doi:10.3390/md12063487
Received: 3 April 2014 / Revised: 18 May 2014 / Accepted: 20 May 2014 / Published: 10 June 2014
Cited by 17 | PDF Full-text (1030 KB) | HTML Full-text | XML Full-text
Abstract
Astaxanthin (3,3′-dihydroxy-β,β-carotene-4,4′-dione), a high-value ketocarotenoid with a broad range of applications in food, feed, nutraceutical, and pharmaceutical industries, has been gaining great attention from science and the public in recent years. The green microalgae Haematococcus pluvialis and Chlorella zofingiensis represent the most promising
[...] Read more.
Astaxanthin (3,3′-dihydroxy-β,β-carotene-4,4′-dione), a high-value ketocarotenoid with a broad range of applications in food, feed, nutraceutical, and pharmaceutical industries, has been gaining great attention from science and the public in recent years. The green microalgae Haematococcus pluvialis and Chlorella zofingiensis represent the most promising producers of natural astaxanthin. Although H. pluvialis possesses the highest intracellular astaxanthin content and is now believed to be a good producer of astaxanthin, it has intrinsic shortcomings such as slow growth rate, low biomass yield, and a high light requirement. In contrast, C. zofingiensis grows fast phototrophically, heterotrophically and mixtrophically, is easy to be cultured and scaled up both indoors and outdoors, and can achieve ultrahigh cell densities. These robust biotechnological traits provide C. zofingiensis with high potential to be a better organism than H. pluvialis for mass astaxanthin production. This review aims to provide an overview of the biology and industrial potential of C. zofingiensis as an alternative astaxanthin producer. The path forward for further expansion of the astaxanthin production from C. zofingiensis with respect to both challenges and opportunities is also discussed. Full article
Open AccessReview Emerging Strategies and Integrated Systems Microbiology Technologies for Biodiscovery of Marine Bioactive Compounds
Mar. Drugs 2014, 12(6), 3516-3559; doi:10.3390/md12063516
Received: 8 April 2014 / Revised: 21 May 2014 / Accepted: 22 May 2014 / Published: 10 June 2014
Cited by 13 | PDF Full-text (1657 KB) | HTML Full-text | XML Full-text
Abstract
Marine microorganisms continue to be a source of structurally and biologically novel compounds with potential use in the biotechnology industry. The unique physiochemical properties of the marine environment (such as pH, pressure, temperature, osmolarity) and uncommon functional groups (such as isonitrile, dichloroimine, isocyanate,
[...] Read more.
Marine microorganisms continue to be a source of structurally and biologically novel compounds with potential use in the biotechnology industry. The unique physiochemical properties of the marine environment (such as pH, pressure, temperature, osmolarity) and uncommon functional groups (such as isonitrile, dichloroimine, isocyanate, and halogenated functional groups) are frequently found in marine metabolites. These facts have resulted in the production of bioactive substances with different properties than those found in terrestrial habitats. In fact, the marine environment contains a relatively untapped reservoir of bioactivity. Recent advances in genomics, metagenomics, proteomics, combinatorial biosynthesis, synthetic biology, screening methods, expression systems, bioinformatics, and the ever increasing availability of sequenced genomes provides us with more opportunities than ever in the discovery of novel bioactive compounds and biocatalysts. The combination of these advanced techniques with traditional techniques, together with the use of dereplication strategies to eliminate known compounds, provides a powerful tool in the discovery of novel marine bioactive compounds. This review outlines and discusses the emerging strategies for the biodiscovery of these bioactive compounds. Full article
Open AccessReview Quinone and Hydroquinone Metabolites from the Ascidians of the Genus Aplidium
Mar. Drugs 2014, 12(6), 3608-3633; doi:10.3390/md12063608
Received: 1 April 2014 / Revised: 3 June 2014 / Accepted: 4 June 2014 / Published: 12 June 2014
Cited by 4 | PDF Full-text (2024 KB) | HTML Full-text | XML Full-text
Abstract
Ascidians of the genus Aplidium are recognized as an important source of chemical diversity and bioactive natural products. Among the compounds produced by this genus are non-nitrogenous metabolites, mainly prenylated quinones and hydroquinones. This review discusses the isolation, structural elucidation, and biological activities
[...] Read more.
Ascidians of the genus Aplidium are recognized as an important source of chemical diversity and bioactive natural products. Among the compounds produced by this genus are non-nitrogenous metabolites, mainly prenylated quinones and hydroquinones. This review discusses the isolation, structural elucidation, and biological activities of quinones, hydroquinones, rossinones, longithorones, longithorols, floresolides, scabellones, conicaquinones, aplidinones, thiaplidiaquinones, and conithiaquinones. A compilation of the 13C-NMR spectral data of these compounds is also presented. Full article
(This article belongs to the collection Bioactive Compounds from Marine Invertebrates)
Open AccessReview Total Synthesis and Structure-Activity Relationship of Glycoglycerolipids from Marine Organisms
Mar. Drugs 2014, 12(6), 3634-3659; doi:10.3390/md12063634
Received: 30 April 2014 / Revised: 29 May 2014 / Accepted: 10 June 2014 / Published: 18 June 2014
Cited by 7 | PDF Full-text (3632 KB) | HTML Full-text | XML Full-text
Abstract
Glycoglycerolipids occur widely in natural products, especially in the marine species. Glycoglycerolipids have been shown to possess a variety of bioactivities. This paper will review the different methodologies and strategies for the synthesis of biological glycoglycerolipids and their analogs for bioactivity assay. In
[...] Read more.
Glycoglycerolipids occur widely in natural products, especially in the marine species. Glycoglycerolipids have been shown to possess a variety of bioactivities. This paper will review the different methodologies and strategies for the synthesis of biological glycoglycerolipids and their analogs for bioactivity assay. In addition, the bioactivities and structure-activity relationship of the glycoglycerolipids are also briefly outlined. Full article
Open AccessReview Siphonaxanthin, a Green Algal Carotenoid, as a Novel Functional Compound
Mar. Drugs 2014, 12(6), 3660-3668; doi:10.3390/md12063660
Received: 10 March 2014 / Revised: 14 April 2014 / Accepted: 17 April 2014 / Published: 19 June 2014
Cited by 5 | PDF Full-text (168 KB) | HTML Full-text | XML Full-text
Abstract
Siphonaxanthin is a specific keto-carotenoid in green algae whose bio-functional properties are yet to be identified. This review focuses on siphonaxanthin as a bioactive compound and outlines the evidence associated with functionality. Siphonaxanthin has been reported to potently inhibit the viability of human
[...] Read more.
Siphonaxanthin is a specific keto-carotenoid in green algae whose bio-functional properties are yet to be identified. This review focuses on siphonaxanthin as a bioactive compound and outlines the evidence associated with functionality. Siphonaxanthin has been reported to potently inhibit the viability of human leukemia HL-60 cells via induction of apoptosis. In comparison with fucoxanthin, siphonaxanthin markedly reduced cell viability as early as 6 h after treatment. The cellular uptake of siphonaxanthin was 2-fold higher than fucoxanthin. It has been proposed that siphonaxanthin possesses significant anti-angiogenic activity in studies using human umbilical vein endothelial cells and rat aortic ring. The results of these studies suggested that the anti-angiogenic effect of siphonaxanthin is due to the down-regulation of signal transduction by fibroblast growth factor receptor-1 in vascular endothelial cells. Siphonaxanthin also exhibited inhibitory effects on antigen-induced degranulation of mast cells. These findings open up new avenues for future research on siphonaxanthin as a bioactive compound, and additional investigation, especially in vivo studies, are required to validate these findings. In addition, further studies are needed to determine its bioavailability and metabolic fate. Full article
(This article belongs to the Special Issue Marine Carotenoids (Special Issue))

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