Marine Drugs

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Open AccessArticle

Anti-Inflammatory Effects of a Mytilus coruscus α-d-Glucan (MP-A) in Activated Macrophage Cells via TLR4/NF-κB/MAPK Pathway Inhibition

by Fuyan Liu, Xiaofeng Zhang, Yuqiu Li, Qixin Chen, Fei Liu, Xiqiang Zhu, Li Mei, Xinlei Song, Xia Liu, Zhigang Song, Jinhua Zhang, Wen Zhang, Peixue Ling and Fengshan Wang

Mar. Drugs 2017, 15(9), 294; https://doi.org/10.3390/md15090294 - 20 Sep 2017

Cited by 22 | Viewed by 6746

Abstract

The hard-shelled mussel (Mytilus coruscus) has been used as Chinese traditional medicine for thousands of years; however, to date the ingredients responsible for the various beneficial health outcomes attributed to Mytilus coruscus are still unclear. An α-d-Glucan, called MP-A, [...] Read more.

The hard-shelled mussel (Mytilus coruscus) has been used as Chinese traditional medicine for thousands of years; however, to date the ingredients responsible for the various beneficial health outcomes attributed to Mytilus coruscus are still unclear. An α-d-Glucan, called MP-A, was isolated from Mytilus coruscus, and observed to exert anti-inflammatory activity in THP-1 human macrophage cells. Specifically, we showed that MP-A treatment inhibited the production of inflammatory markers, including TNF-α, NO, and PGE2, inducible NOS (iNOS), and cyclooxygenase-2 (COX-2), in LPS-activated THP-1 cells. It was also shown to enhance phagocytosis in the analyzed cells, but to severely inhibit the phosphorylation of mitogen-activated protein kinases (MAPKs) and the nuclear translocation of NF-κB P65. Finally, MP-A was found to exhibit a high binding affinity for the cell surface receptor TLR4, but a low affinity for TLR2 and dectin-1, via surface plasmon resonance (SPR) analysis. The study indicates that MP-A suppresses LPS-induced TNF-α, NO and PEG2 production via TLR4/NF-κB/MAPK pathway inhibition, and suggests that MP-A may be a promising therapeutic candidate for diseases associated with TNF-α, NO, and/or PEG2 overproduction. Full article

(This article belongs to the Special Issue Marine Anti-inflammatory Agents)

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Open AccessArticle

Proteomic Analysis of the Chlorophyta Dunaliella New Strain AL-1 Revealed Global Changes of Metabolism during High Carotenoid Production

by Faten Ben Amor, Fatma Elleuch, Hajer Ben Hlima, Matthieu Garnier, Bruno Saint-Jean, Mohamed Barkallah, Chantal Pichon, Slim Abdelkafi and Imen Fendri

Mar. Drugs 2017, 15(9), 293; https://doi.org/10.3390/md15090293 - 20 Sep 2017

Cited by 24 | Viewed by 5379

Abstract

The green microalgae Dunaliella genus is known for the production of high added value molecules. In this study, strain AL-1 was isolated from the Sebkha of Sidi El Hani (Sousse, Tunisia). This isolate was identified both morphologically and genetically via 18S rRNA gene [...] Read more.

The green microalgae Dunaliella genus is known for the production of high added value molecules. In this study, strain AL-1 was isolated from the Sebkha of Sidi El Hani (Sousse, Tunisia). This isolate was identified both morphologically and genetically via 18S rRNA gene sequence as a member of the genus Dunaliella. Strain AL-1 was found to be closely related to Dunaliella salina, Dunaliella quartolecta and Dunaliella polymorpha with more than 97% similarity. Response surface methodology was used to maximize carotenoid production by strain AL-1 by optimizing its growth conditions. The highest carotenoid content was obtained at salinity: 51, light intensity: 189.89 μmol photons·m⁻²·s⁻¹, and nitrogen: 60 mg·L⁻¹. Proteomic profiling, using two-dimensional gel electrophoresis, was performed from standard and optimized cultures. We detected 127 protein spots which were significantly differentially expressed between standard and optimized cultures. Among them 16 protein spots were identified with mass spectrometry and grouped into different functional categories using KEGG (Kyoto Encyclopedia of Genes and Genomes) such as photosynthetic Calvin cycle, regulation/defense, energy metabolism, glycolysis, and cellular processes. The current study could be of great interest in providing information on the effect of stressful conditions in microalgae carotenoid production. Full article

(This article belongs to the Collection Bioactive Compounds from Marine Plankton)

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Open AccessCorrection

Correction: Zhang, G.; Cheng, G.; Jia, P.; Jiao, S.; Feng, C.; Hu, T.; Liu, H.; Du, Y. The Positive Correlation of the Enhanced Immune Response to PCV2 Subunit Vaccine by Conjugation of Chitosan Oligosaccharide with the Deacetylation Degree. Marine Drugs 2017, 15, 236

by Guiqiang Zhang, Gong Cheng, Peiyuan Jia, Siming Jiao, Cui Feng, Tao Hu, Hongtao Liu and Yuguang Du

Mar. Drugs 2017, 15(9), 292; https://doi.org/10.3390/md15090292 - 20 Sep 2017

Cited by 3 | Viewed by 3285

Abstract

The authors wish to correct Figure 1 in this paper [1] to be as follows:[...] Full article

(This article belongs to the Special Issue Marine Oligosaccharides and Polysaccharides)

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Open AccessArticle

Chemical Synthesis of Marine-Derived Sulfoglycolipids, a New Class of Molecular Adjuvants

by Emiliano Manzo, Laura Fioretto, Dario Pagano, Genoveffa Nuzzo, Carmela Gallo, Raffaele De Palma and Angelo Fontana

Mar. Drugs 2017, 15(9), 288; https://doi.org/10.3390/md15090288 - 20 Sep 2017

Cited by 15 | Viewed by 4609

Abstract

Vaccines play a primary role in the protection of human health by preventing infectious and chronic diseases. Recently we have reported 1,2-O-distearoyl-3-O-β-d-sulfoquinovosylglycerol (β-SQDG18), here named Sulfavant A (1), which shows promising properties as a new [...] Read more.

Vaccines play a primary role in the protection of human health by preventing infectious and chronic diseases. Recently we have reported 1,2-O-distearoyl-3-O-β-d-sulfoquinovosylglycerol (β-SQDG18), here named Sulfavant A (1), which shows promising properties as a new molecular adjuvant in in vitro and in vivo tests. In the present manuscript, we provide full details about a synthetic strategy for the preparation of 1, including a discussion of chemical determinants of the activity and the major technical hurdles we faced during the study. Synthesis of Sulfavant A (1) is achieved by a versatile procedure based on a trichloroacetimidate methodology and peracetate sugar precursors. The final design opens possibilities for the preparation of a series of interesting analogs for further pharmacological optimization and development, including derivatives containing different saturated and polyunsaturated fatty acids (e.g., 17 and 22). Full article

(This article belongs to the Special Issue Target Identification of Marine Products)

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Open AccessArticle

3-Bromo-4,5-dihydroxybenzaldehyde Enhances the Level of Reduced Glutathione via the Nrf2-Mediated Pathway in Human Keratinocytes

by Ki Cheon Kim, Yu Jae Hyun, Susara Ruwan Kumara Madduma Hewage, Mei Jing Piao, Kyoung Ah Kang, Hee Kyoung Kang, Young Sang Koh, Mee Jung Ahn and Jin Won Hyun

Mar. Drugs 2017, 15(9), 291; https://doi.org/10.3390/md15090291 - 18 Sep 2017

Cited by 19 | Viewed by 4800

Abstract

A natural bromophenol found in seaweeds, 3-bromo-4,5-dihydroxybenzaldehyde (BDB), has been shown to possess antioxidant effects. This study aimed to investigate the mechanism by which BDB protects skin cells subjected to oxidative stress. The effect of BDB on the protein and mRNA levels of [...] Read more.

A natural bromophenol found in seaweeds, 3-bromo-4,5-dihydroxybenzaldehyde (BDB), has been shown to possess antioxidant effects. This study aimed to investigate the mechanism by which BDB protects skin cells subjected to oxidative stress. The effect of BDB on the protein and mRNA levels of glutathione-related enzymes and the cell survival of human keratinocytes (HaCaT cells) was investigated. BDB treatment increased the protein and mRNA levels of glutathione synthesizing enzymes and enhanced the production of reduced glutathione in HaCaT cells. Furthermore, BDB activated NF-E2-related factor 2 (Nrf2) and promoted its localization into the nucleus by phosphorylating its up-stream signaling proteins, extracellular signal–regulated kinase and protein kinase B. Thus, BDB increased the production of reduced glutathione and established cellular protection against oxidative stress via an Nrf2-mediated pathway. Full article

(This article belongs to the Special Issue Seaweeds and Their Biological Actions)

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Open AccessArticle

Kempopeptin C, a Novel Marine-Derived Serine Protease Inhibitor Targeting Invasive Breast Cancer

by Fatma H. Al-Awadhi, Lilibeth A. Salvador, Brian K. Law, Valerie J. Paul and Hendrik Luesch

Mar. Drugs 2017, 15(9), 290; https://doi.org/10.3390/md15090290 - 16 Sep 2017

Cited by 29 | Viewed by 5971

Abstract

Kempopeptin C, a novel chlorinated analogue of kempopeptin B, was discovered from a marine cyanobacterium collected from Kemp Channel in Florida. The structure was elucidated using NMR spectroscopy and mass spectrometry (MS). The presence of the basic Lys residue adjacent to the N [...] Read more.

Kempopeptin C, a novel chlorinated analogue of kempopeptin B, was discovered from a marine cyanobacterium collected from Kemp Channel in Florida. The structure was elucidated using NMR spectroscopy and mass spectrometry (MS). The presence of the basic Lys residue adjacent to the N-terminus of the 3-amino-6-hydroxy-2-piperidone (Ahp) moiety contributed to its selectivity towards trypsin and related proteases. The antiproteolytic activity of kempopeptin C was evaluated against trypsin, plasmin and matriptase and found to inhibit these enzymes with IC₅₀ values of 0.19, 0.36 and 0.28 μM, respectively. Due to the significance of these proteases in cancer progression and metastasis, as well as their functional redundancy with respect to targeting overlapping substrates, we examined the effect of kempopeptin C on the downstream cellular substrates of matriptase: CDCP1 and desmoglein-2 (Dsg-2). Kempopeptin C was shown to inhibit the cleavage of both substrates in vitro. Additionally, kempopeptin C reduced the cleavage of CDCP1 in MDA-MB-231 cells up to 10 µM. The functional relevance of targeting matriptase and related proteases was investigated by assessing the effect of kempopeptin C on the migration of breast cancer cells. Kempopeptin C inhibited the migration of the invasive MDA-MB-231 cells by 37 and 60% at 10 and 20 µM, respectively. Full article

(This article belongs to the Special Issue Marine Drugs as Antitumour Agents 2017)

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Open AccessArticle

Leptolide Improves Insulin Resistance in Diet-Induced Obese Mice

by Pablo Villa-Pérez, Mercedes Cueto, Ana R. Díaz-Marrero, Carmen D. Lobatón, Alfredo Moreno, Germán Perdomo and Irene Cózar-Castellano

Mar. Drugs 2017, 15(9), 289; https://doi.org/10.3390/md15090289 - 15 Sep 2017

Cited by 5 | Viewed by 4403

Abstract

Type 2 diabetes (T2DM) is a complex disease linked to pancreatic beta-cell failure and insulin resistance. Current antidiabetic treatment regimens for T2DM include insulin sensitizers and insulin secretagogues. We have previously demonstrated that leptolide, a member of the furanocembranolides family, promotes pancreatic beta-cell [...] Read more.

Type 2 diabetes (T2DM) is a complex disease linked to pancreatic beta-cell failure and insulin resistance. Current antidiabetic treatment regimens for T2DM include insulin sensitizers and insulin secretagogues. We have previously demonstrated that leptolide, a member of the furanocembranolides family, promotes pancreatic beta-cell proliferation in mice. Considering the beneficial effects of leptolide in diabetic mice, in this study, we aimed to address the capability of leptolide to improve insulin resistance associated with the pathology of obesity. To this end, we tested the hypothesis that leptolide should protect against fatty acid-induced insulin resistance in hepatocytes. In a time-dependent manner, leptolide (0.1 µM) augmented insulin-stimulated phosphorylation of protein kinase B (PKB) by two-fold above vehicle-treated HepG2 cells. In addition, leptolide (0.1 µM) counteracted palmitate-induced insulin resistance by augmenting by four-fold insulin-stimulated phosphorylation of PKB in HepG2 cells. In vivo, acute intraperitoneal administration of leptolide (0.1 mg/kg and 1 mg/kg) improved glucose tolerance and insulin sensitivity in lean mice. Likewise, prolonged leptolide treatment (0.1 mg/kg) in diet-induced obese mice improved insulin sensitivity. These effects were paralleled with an ~50% increased of insulin-stimulated phosphorylation of PKB in liver and skeletal muscle and reduced circulating pro-inflammatory cytokines in obese mice. We concluded that leptolide significantly improves insulin sensitivity in vitro and in obese mice, suggesting that leptolide may be another potential treatment for T2DM. Full article

(This article belongs to the Special Issue Marine Compounds and Inflammation II, 2017)

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Open AccessArticle

APETx4, a Novel Sea Anemone Toxin and a Modulator of the Cancer-Relevant Potassium Channel K_V10.1

by Lien Moreels, Steve Peigneur, Diogo T. Galan, Edwin De Pauw, Lászlo Béress, Etienne Waelkens, Luis A. Pardo, Loïc Quinton and Jan Tytgat

Mar. Drugs 2017, 15(9), 287; https://doi.org/10.3390/md15090287 - 13 Sep 2017

Cited by 32 | Viewed by 6176

Abstract

The human ether-à-go-go channel (hEag1 or K_V10.1) is a cancer-relevant voltage-gated potassium channel that is overexpressed in a majority of human tumors. Peptides that are able to selectively inhibit this channel can be lead compounds in the search for new anticancer [...] Read more.

The human ether-à-go-go channel (hEag1 or K_V10.1) is a cancer-relevant voltage-gated potassium channel that is overexpressed in a majority of human tumors. Peptides that are able to selectively inhibit this channel can be lead compounds in the search for new anticancer drugs. Here, we report the activity-guided purification and electrophysiological characterization of a novel K_V10.1 inhibitor from the sea anemone Anthopleura elegantissima. Purified sea anemone fractions were screened for inhibitory activity on K_V10.1 by measuring whole-cell currents as expressed in Xenopus laevis oocytes using the two-microelectrode voltage clamp technique. Fractions that showed activity on Kv10.1 were further purified by RP-HPLC. The amino acid sequence of the peptide was determined by a combination of MALDI- LIFT-TOF/TOF MS/MS and CID-ESI-FT-ICR MS/MS and showed a high similarity with APETx1 and APETx3 and was therefore named APETx4. Subsequently, the peptide was electrophysiologically characterized on K_V10.1. The selectivity of the toxin was investigated on an array of voltage-gated ion channels, including the cardiac human ether-à-go-go-related gene potassium channel (hERG or Kv11.1). The toxin inhibits K_V10.1 with an IC₅₀ value of 1.1 μM. In the presence of a similar toxin concentration, a shift of the activation curve towards more positive potentials was observed. Similar to the effect of the gating modifier toxin APETx1 on hERG, the inhibition of Kv10.1 by the isolated toxin is reduced at more positive voltages and the peptide seems to keep the channel in a closed state. Although the peptide also induces inhibitory effects on other K_V and Na_V channels, it exhibits no significant effect on hERG. Moreover, APETx4 induces a concentration-dependent cytotoxic and proapoptotic effect in various cancerous and noncancerous cell lines. This newly identified K_V10.1 inhibitor can be used as a tool to further characterize the oncogenic channel K_V10.1 or as a scaffold for the design and synthesis of more potent and safer anticancer drugs. Full article

(This article belongs to the Special Issue Marine Invertebrate Toxins)

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Open AccessArticle

Biodiversity of Actinobacteria from the South Pacific and the Assessment of Streptomyces Chemical Diversity with Metabolic Profiling

by Andrés Cumsille, Agustina Undabarrena, Valentina González, Fernanda Claverías, Claudia Rojas and Beatriz Cámara

Mar. Drugs 2017, 15(9), 286; https://doi.org/10.3390/md15090286 - 11 Sep 2017

Cited by 30 | Viewed by 7230

Abstract

Recently, bioprospecting in underexplored habitats has gained enhanced focus, since new taxa of marine actinobacteria can be found, and thus possible new metabolites. Actinobacteria are in the foreground due to their versatile production of secondary metabolites that present various biological activities, such as [...] Read more.

Recently, bioprospecting in underexplored habitats has gained enhanced focus, since new taxa of marine actinobacteria can be found, and thus possible new metabolites. Actinobacteria are in the foreground due to their versatile production of secondary metabolites that present various biological activities, such as antibacterials, antitumorals and antifungals. Chilean marine ecosystems remain largely unexplored and may represent an important source for the discovery of bioactive compounds. Various culture conditions to enrich the growth of this phylum were used and 232 bacterial strains were isolated. Comparative analysis of the 16S rRNA gene sequences led to identifying genetic affiliations of 32 genera, belonging to 20 families. This study shows a remarkable culturable diversity of actinobacteria, associated to marine environments along Chile. Furthermore, 30 streptomycete strains were studied to establish their antibacterial activities against five model strains, Staphylococcus aureus, Listeria monocytogenes, Salmonella enterica, Escherichia coli and Pseudomonas aeruginosa, demonstrating abilities to inhibit bacterial growth of Gram-positive bacteria. To gain insight into their metabolic profiles, crude extracts were submitted to liquid chromatography-high resolution mass spectrometry (LC-HRMS) analysis to assess the selection of streptomycete strains with potentials of producing novel bioactive metabolites. The combined approach allowed for the identification of three streptomycete strains to pursue further investigations. Our Chilean marine actinobacterial culture collection represents an important resource for the bioprospection of novel marine actinomycetes and its metabolites, evidencing their potential as producers of natural bioproducts. Full article

(This article belongs to the Special Issue Antibacterial Marine Pharmacology)

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Open AccessReview

Biogenetic Relationships of Bioactive Sponge Merotriterpenoids

by Thomas E. Smith

Mar. Drugs 2017, 15(9), 285; https://doi.org/10.3390/md15090285 - 10 Sep 2017

Cited by 8 | Viewed by 5680

Abstract

Hydroquinone meroterpenoids, especially those derived from marine sponges, display a wide range of biological activities. However, use of these compounds is limited by their inaccessibility; there is no sustainable supply of these compounds. Furthermore, our knowledge of their metabolic origin remains completely unstudied. [...] Read more.

Hydroquinone meroterpenoids, especially those derived from marine sponges, display a wide range of biological activities. However, use of these compounds is limited by their inaccessibility; there is no sustainable supply of these compounds. Furthermore, our knowledge of their metabolic origin remains completely unstudied. In this review, an in depth structural analysis of sponge merotriterpenoids, including the adociasulfate family of kinesin motor protein inhibitors, provides insight into their biosynthesis. Several key structural features provide clues to the relationships between compounds. All adociasulfates appear to be derived from only four different hydroquinone hexaprenyl diphosphate precursors, each varying in the number and position of epoxidations. Proton-initiated cyclization of these precursors can lead to all carbon skeletons observed amongst sponge merotriterpenoids. Consideration of the enzymes involved in the proposed biosynthetic route suggests a bacterial source, and a hypothetical gene cluster was constructed that may facilitate discovery of the authentic pathway from the sponge metagenome. A similar rationale can be extended to other sponge meroterpenoids, for which no biosynthetic pathways have yet been identified. Full article

(This article belongs to the Special Issue Genome Mining and Marine Microbial Natural Products)

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Open AccessArticle

Construction of a Fluorescent H₂O₂ Biosensor with Chitosan 6-OH Immobilized β-Cyclodextrin Derivatives

by Wenbo Dong, Weiping Li, Yu Chen, Yanchun Ye and Shaohua Jin

Mar. Drugs 2017, 15(9), 284; https://doi.org/10.3390/md15090284 - 4 Sep 2017

Cited by 4 | Viewed by 4846

Abstract

In the present work, a fluorescent H₂O₂ biosensor was constructed by encapsulating fluorescent probe Rhodamine B (RhmB) in the hydrophobic cavity of the cyclodextrin (β-CD) and immobilizing catalase (CAT) on the 2-NH₂ of chitosan (CTS) in a chitosan 6-OH [...] Read more.

In the present work, a fluorescent H₂O₂ biosensor was constructed by encapsulating fluorescent probe Rhodamine B (RhmB) in the hydrophobic cavity of the cyclodextrin (β-CD) and immobilizing catalase (CAT) on the 2-NH₂ of chitosan (CTS) in a chitosan 6-OH immobilized β-cyclodextrin derivative (CTS-6-CD). The inclusion complex of CTS-6-CD to RhmB (CTS-6-CD-RhmB) was prepared by a solution method. Its structure and inclusion efficiency were determined by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and fluorescence spectroscopy (FL). CAT was immobilized on CTS-6-CD-RhmB to eventually form the functional membrane, CTS-6-CD-RhmB-CAT, via glutaraldehyde crosslinking, which was further characterized by FTIR and FL, and used as a H₂O₂ biosensor. The functional membrane was used to simultaneously oxidize and detect H₂O₂. The detection condition was optimized as pH 8, a reaction temperature of 25 °C, and an immobilized enzyme concentration of 2 × 10⁻⁴ mol/L. The fluorescence response of the biosensor exhibited a good linear relationship with the concentration of H₂O₂ in the range of 20 mΜ–300 μM and the detection limit of 10⁻⁸ mol/L. Full article

(This article belongs to the Special Issue Marine Products for Health and Beauty)

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Open AccessArticle

Potential Application of Eicosapentaenoic Acid Monoacylglyceride in the Management of Colorectal Cancer

by Caroline Morin, Enrique Rodríguez, Pierre U. Blier and Samuel Fortin

Mar. Drugs 2017, 15(9), 283; https://doi.org/10.3390/md15090283 - 4 Sep 2017

Cited by 24 | Viewed by 4828

Abstract

Background: There is increasing evidence that marine omega-3 oils are involved in the reduction of cancer risk and progression. However, the anticancer effect of omega-3 monoglyceride on colorectal cancer has yet to be assessed. The goal of this study was to evaluate the [...] Read more.

Background: There is increasing evidence that marine omega-3 oils are involved in the reduction of cancer risk and progression. However, the anticancer effect of omega-3 monoglyceride on colorectal cancer has yet to be assessed. The goal of this study was to evaluate the anti-cancer effects of eicosapentaenoic acid monoglyceride (MAG-EPA) in HCT116 colorectal carcinoma cells. Methods: The effect of MAG-EPA was evaluated in vitro on HCT116 cells and in vivo on mouse model of HCT116 xenograft. Results: Our data reveal that MAG-EPA decreased cell proliferation and induced apoptosis in HCT116 cells. In a xenograft mouse model, daily per os administration of MAG-EPA reduced tumor growth. Furthermore, MAG-EPA treatments decreased EGFR, VEGFR, and AKT activation pathways and reduced VEGF and HIF1α expression levels in tumors. Conclusion: MAG-EPA may promote apoptosis and inhibit growth of tumors by suppressing EGFR and VEGFR activation pathways. Altogether, these data provide new evidence regarding the mode of action of MAG-EPA in colorectal cancer cells. Full article

(This article belongs to the Special Issue The Sources and Production of Polyunsaturated Fatty Acids)

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Open AccessArticle

Anti-Inflammatory Effects of Curvularin-Type Metabolites from a Marine-Derived Fungal Strain Penicillium sp. SF-5859 in Lipopolysaccharide-Induced RAW264.7 Macrophages

by Tran Minh Ha, Wonmin Ko, Seung Jun Lee, Youn-Chul Kim, Jae-Young Son, Jae Hak Sohn, Joung Han Yim and Hyuncheol Oh

Mar. Drugs 2017, 15(9), 282; https://doi.org/10.3390/md15090282 - 2 Sep 2017

Cited by 36 | Viewed by 5935

Abstract

Chemical study on the extract of a marine-derived fungal strain Penicillium sp. SF-5859 yielded a new curvularin derivative (1), along with eight known curvularin-type polyketides (2–9). The structures of these metabolites (1–9) were [...] Read more.

Chemical study on the extract of a marine-derived fungal strain Penicillium sp. SF-5859 yielded a new curvularin derivative (1), along with eight known curvularin-type polyketides (2–9). The structures of these metabolites (1–9) were established by comprehensive spectroscopic analyses, including 1D and 2D nuclear magnetic resonance (NMR) spectroscopy, and mass spectrometry (MS). In vitro anti-inflammatory effects of these metabolites were evaluated in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Among these metabolites, 3–9 were shown to strongly inhibit LPS-induced overproduction of nitric oxide (NO) and prostaglandin E₂ (PGE₂) with IC₅₀ values ranging from 1.9 μM to 18.1 μM, and from 2.8 μM to 18.7 μM, respectively. In the further evaluation of signal pathways involved in these effects, the most active compound, (10E,15S)-10,11-dehydrocurvularin (8) attenuated the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated RAW264.7 macrophages. Furthermore, compound 8 was shown to suppress the upregulation of pro-inflammatory mediators and cytokines via the inhibition of the nuclear factor-κB (NF-κB) signaling pathway, but not through the mitogen-activated protein kinase (MAPK) pathway. Based on the comparisons of the different magnitude of the anti-inflammatory effects of these structurally-related metabolites, it was suggested that the opening of the 12-membered lactone ring in curvularin-type metabolites and blocking the phenol functionality led to the significant decrease in their anti-inflammatory activity. Full article

(This article belongs to the Special Issue Marine Compounds and Inflammation II, 2017)

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Open AccessArticle

Biological and Chemical Diversity of Bacteria Associated with a Marine Flatworm

by Hui-Na Lin, Kai-Ling Wang, Ze-Hong Wu, Ren-Mao Tian, Guo-Zhu Liu and Ying Xu

Mar. Drugs 2017, 15(9), 281; https://doi.org/10.3390/md15090281 - 1 Sep 2017

Cited by 19 | Viewed by 4892

Abstract

The aim of this research is to explore the biological and chemical diversity of bacteria associated with a marine flatworm Paraplanocera sp., and to discover the bioactive metabolites from culturable strains. A total of 141 strains of bacteria including 45 strains of actinomycetes [...] Read more.

The aim of this research is to explore the biological and chemical diversity of bacteria associated with a marine flatworm Paraplanocera sp., and to discover the bioactive metabolites from culturable strains. A total of 141 strains of bacteria including 45 strains of actinomycetes and 96 strains of other bacteria were isolated, identified and fermented on a small scale. Bioactive screening (antibacterial and cytotoxic activities) and chemical screening (ultra-performance liquid chromatography–mass spectrometry (UPLC-MS)) yielded several target bacterial strains. Among these strains, the ethyl acetate (EA) crude extract of Streptomyces sp. XY-FW47 fermentation broth showed strong antibacterial activity against methicillin-resistant Staphylococcus aureus ATCC43300 (MRSA ATCC43300) and potent cytotoxic effects on HeLa cells. The UPLC-MS spectral analysis of the crude extract indicated that the strain XY-FW47 could produce a series of geldanamycins (GMs). One new geldanamycin (GM) analog, 4,5-dihydro-17-O-demethylgeldanamycin (1), and three known GMs (2–4) were obtained. All of these compounds were tested for antibacterial, cytotoxic, and antifungal activities, yet only GM (3) showed potent cytotoxic (HeLa cells, EC₅₀ = 1.12 μg/mL) and antifungal (Setosphaeria turcica MIC = 2.40 μg/mL) activities. Their structure–activity relationship (SAR) was also preliminarily discussed in this study. Full article

(This article belongs to the Special Issue Bioactive Compounds from Marine Microbes - II)

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Open AccessArticle

Bioactive Steroids with Methyl Ester Group in the Side Chain from a Reef Soft Coral Sinularia brassica Cultured in a Tank

by Chiung-Yao Huang, Jui-Hsin Su, Chih-Chuang Liaw, Ping-Jyun Sung, Pei-Lun Chiang, Tsong-Long Hwang, Chang-Feng Dai and Jyh-Horng Sheu

Mar. Drugs 2017, 15(9), 280; https://doi.org/10.3390/md15090280 - 1 Sep 2017

Cited by 23 | Viewed by 4958

Abstract

A continuing chemical investigation of the ethyl acetate (EtOAc) extract of a reef soft coral Sinularia brassica, which was cultured in a tank, afforded four new steroids with methyl ester groups, sinubrasones A–D (1–4) for the first time. In particular, 1 [...] Read more.

A continuing chemical investigation of the ethyl acetate (EtOAc) extract of a reef soft coral Sinularia brassica, which was cultured in a tank, afforded four new steroids with methyl ester groups, sinubrasones A–D (1–4) for the first time. In particular, 1 possesses a β-D-xylopyranose. The structures of the new compounds were elucidated on the basis of spectroscopic analyses. The cytotoxicities of compounds 1–4 against the proliferation of a limited panel of cancer cell lines were assayed. The anti-inflammatory activities of these new compounds 1–4 were also evaluated by measuring their ability to suppress superoxide anion generation and elastase release in N-formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLP/CB)-induced human neutrophils. Compounds 2 and 3 were shown to exhibit significant cytotoxicity, and compounds 3 and 4 were also found to display attracting anti-inflammatory activities. Full article

(This article belongs to the Special Issue Natural Products from Coral Reef Organisms)

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Open AccessArticle

Pharmacokinetics of Jaspine B and Enhancement of Intestinal Absorption of Jaspine B in the Presence of Bile Acid in Rats

by Min-Koo Choi, Jihoon Lee, So Jeong Nam, Yun Ju Kang, Youjin Han, Kwangik Choi, Young A. Choi, Mihwa Kwon, Dongjoo Lee and Im-Sook Song

Mar. Drugs 2017, 15(9), 279; https://doi.org/10.3390/md15090279 - 1 Sep 2017

Cited by 7 | Viewed by 4100

Abstract

We aimed to investigate the pharmacokinetics and the underlying mechanisms of the intestinal absorption, distribution, metabolism, and excretion of Jaspine B in rats. The oral bioavailability of Jaspine B was 6.2%, but it decreased to 1.6% in bile-depleted rats and increased to 41.2% [...] Read more.

We aimed to investigate the pharmacokinetics and the underlying mechanisms of the intestinal absorption, distribution, metabolism, and excretion of Jaspine B in rats. The oral bioavailability of Jaspine B was 6.2%, but it decreased to 1.6% in bile-depleted rats and increased to 41.2% (normal) and 23.5% (bile-depleted) with taurocholate supplementation (60 mg/kg). Consistent with the increased absorption in the presence of bile salts, rat intestinal permeability of Jaspine B also increased in the presence of 10 mM taurocholate or 20% bile. Further studies demonstrated that the enhanced intestinal permeability with bile salts was due to increased lipophilicity and decreased membrane integrity. Jaspine B was designated as a highly tissue-distributed compound, because it showed large tissue to plasma ratios in the brain, kidney, heart, and spleen. Moreover, the recovery of Jaspine B from the feces and urine after an intravenous administration was about 6.3%, suggesting a substantial metabolism of Jaspine B. Consistent with this observation, 80% of the administered Jaspine B was degraded after 1 h incubation with rat liver microsomes. In conclusion, the facilitated intestinal permeability in the presence of bile salts could significantly increase the bioavailability of Jaspine B and could lead to the development of oral formulations of Jaspine B with bile salts. Moreover, the highly distributed features of Jaspine B in the brain, kidney, heart, and spleen should be carefully considered in the therapeutic effect and toxicity of this compound. Full article

(This article belongs to the Special Issue Development and Application of Herbal Medicine from Marine Origin)

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Open AccessArticle

HPLC-HRMS Quantification of the Ichthyotoxin Karmitoxin from Karlodinium armiger

by Aaron John Christian Andersen, Lívia Soman De Medeiros, Sofie Bjørnholt Binzer, Silas Anselm Rasmussen, Per Juel Hansen, Kristian Fog Nielsen, Kevin Jørgensen and Thomas Ostenfeld Larsen

Mar. Drugs 2017, 15(9), 278; https://doi.org/10.3390/md15090278 - 31 Aug 2017

Cited by 11 | Viewed by 5942

Abstract

Being able to quantify ichthyotoxic metabolites from microalgae allows for the determination of ecologically-relevant concentrations that can be simulated in laboratory experiments, as well as to investigate bioaccumulation and degradation. Here, the ichthyotoxin karmitoxin, produced by Karlodinium armiger, was quantified in laboratory-grown [...] Read more.

Being able to quantify ichthyotoxic metabolites from microalgae allows for the determination of ecologically-relevant concentrations that can be simulated in laboratory experiments, as well as to investigate bioaccumulation and degradation. Here, the ichthyotoxin karmitoxin, produced by Karlodinium armiger, was quantified in laboratory-grown cultures using high-performance liquid chromatography (HPLC) coupled to electrospray ionisation high-resolution time-of-flight mass spectrometry (HRMS). Prior to the quantification of karmitoxin, a standard of karmitoxin was purified from K. armiger cultures (80 L). The standard was quantified by fluorescent derivatisation using Waters AccQ-Fluor reagent and derivatised fumonisin B₁ and fumonisin B₂ as standards, as each contain a primary amine. Various sample preparation methods for whole culture samples were assessed, including six different solid phase extraction substrates. During analysis of culture samples, MS source conditions were monitored with chloramphenicol and valinomycin as external standards over prolonged injection sequences (>12 h) and karmitoxin concentrations were determined using the response factor of a closely eluting iturin A2 internal standard. Using this method the limit of quantification was 0.11 μg·mL⁻¹, and the limit of detection was found to be 0.03 μg·mL⁻¹. Matrix effects were determined with the use of K. armiger cultures grown with ¹³C-labelled bicarbonate as the primary carbon source. Full article

(This article belongs to the Special Issue Harmful Marine Phytoplankton)

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2014 KiB

Open AccessArticle

Detection of Tetrodotoxin Shellfish Poisoning (TSP) Toxins and Causative Factors in Bivalve Molluscs from the UK

by Andrew D. Turner, Monika Dhanji-Rapkova, Lewis Coates, Lesley Bickerstaff, Steve Milligan, Alison O’Neill, Dermot Faulkner, Hugh McEneny, Craig Baker-Austin, David N. Lees and Myriam Algoet

Mar. Drugs 2017, 15(9), 277; https://doi.org/10.3390/md15090277 - 30 Aug 2017

Cited by 70 | Viewed by 8840

Abstract

Tetrodotoxins (TTXs) are traditionally associated with the occurrence of tropical Pufferfish Poisoning. In recent years, however, TTXs have been identified in European bivalve mollusc shellfish, resulting in the need to assess prevalence and risk to shellfish consumers. Following the previous identification of TTXs [...] Read more.

Tetrodotoxins (TTXs) are traditionally associated with the occurrence of tropical Pufferfish Poisoning. In recent years, however, TTXs have been identified in European bivalve mollusc shellfish, resulting in the need to assess prevalence and risk to shellfish consumers. Following the previous identification of TTXs in shellfish from southern England, this study was designed to assess the wider prevalence of TTXs in shellfish from around the coast of the UK. Samples were collected between 2014 and 2016 and subjected to analysis using HILIC-MS/MS. Results showed the continued presence of toxins in shellfish harvested along the coast of southern England, with the maximum concentration of total TTXs reaching 253 µg/kg. TTX accumulation was detected in Pacific oysters (Crassostrea gigas), native oysters (Ostrea edulis) common mussels (Mytilus edulis) and hard clams (Mercenaria mercenaria), but not found in cockles (Cerastoderma edule), razors (Ensis species) or scallops (Pecten maximus). Whilst the highest concentrations were quantified in samples harvested during the warmer summer months, TTXs were still evident during the winter. An assessment of the potential causative factors did not reveal any links with the phytoplankton species Prorocentrum cordatum, instead highlighting a greater level of risk in areas of shallow, estuarine waters with temperatures above 15 °C. Full article

(This article belongs to the Special Issue Tetrodotoxin)

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Open AccessArticle

Palladium-Catalyzed Dehydrogenative Coupling: An Efficient Synthetic Strategy for the Construction of the Quinoline Core

by Asier Carral-Menoyo, Verónica Ortiz-de-Elguea, Mikel Martinez-Nunes, Nuria Sotomayor and Esther Lete

Mar. Drugs 2017, 15(9), 276; https://doi.org/10.3390/md15090276 - 30 Aug 2017

Cited by 11 | Viewed by 5612

Abstract

Palladium-catalyzed dehydrogenative coupling is an efficient synthetic strategy for the construction of quinoline scaffolds, a privileged structure and prevalent motif in many natural and biologically active products, in particular in marine alkaloids. Thus, quinolines and 1,2-dihydroquinolines can be selectively obtained in moderate-to-good yields [...] Read more.

Palladium-catalyzed dehydrogenative coupling is an efficient synthetic strategy for the construction of quinoline scaffolds, a privileged structure and prevalent motif in many natural and biologically active products, in particular in marine alkaloids. Thus, quinolines and 1,2-dihydroquinolines can be selectively obtained in moderate-to-good yields via intramolecular C–H alkenylation reactions, by choosing the reaction conditions. This methodology provides a direct method for the construction of this type of quinoline through an efficient and atom economical procedure, and constitutes significant advance over the existing procedures that require preactivated reaction partners. Full article

(This article belongs to the Special Issue Bioactive Marine Natural Compounds with Heterocyclic Motifs in their Structure)

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Open AccessArticle

FVIIa-sTF and Thrombin Inhibitory Activities of Compounds Isolated from Microcystis aeruginosa K-139

by Andrea Roxanne J. Anas, Akane Mori, Mineka Tone, Chiaki Naruse, Anna Nakajima, Hirohiko Asukabe, Yoshiaki Takaya, Susumu Y. Imanishi, Tomoyasu Nishizawa, Makoto Shirai and Ken-ichi Harada

Mar. Drugs 2017, 15(9), 275; https://doi.org/10.3390/md15090275 - 30 Aug 2017

Cited by 5 | Viewed by 4912

Abstract

The rise of bleeding and bleeding complications caused by oral anticoagulant use are serious problems nowadays. Strategies that block the initiation step in blood coagulation involving activated factor VII-tissue factor (fVIIa-TF) have been considered. This study explores toxic Microcystis aeruginosa K-139, from Lake [...] Read more.

The rise of bleeding and bleeding complications caused by oral anticoagulant use are serious problems nowadays. Strategies that block the initiation step in blood coagulation involving activated factor VII-tissue factor (fVIIa-TF) have been considered. This study explores toxic Microcystis aeruginosa K-139, from Lake Kasumigaura, Ibaraki, Japan, as a promising cyanobacterium for isolation of fVIIa-sTF inhibitors. M. aeruginosa K-139 underwent reversed-phase solid-phase extraction (ODS-SPE) from 20% MeOH to MeOH elution with 40%-MeOH increments, which afforded aeruginosin K-139 in the 60% MeOH fraction; micropeptin K-139 and microviridin B in the MeOH fraction. Aeruginosin K-139 displayed an fVIIa-sTF inhibitory activity of ~166 µM, within a 95% confidence interval. Micropeptin K-139 inhibited fVIIa-sTF with EC₅₀ 10.62 µM, which was more efficient than thrombin inhibition of EC₅₀ 26.94 µM. The thrombin/fVIIa-sTF ratio of 2.54 in micropeptin K-139 is higher than those in 4-amidinophenylmethane sulfonyl fluoride (APMSF) and leupeptin, when used as positive controls. This study proves that M. aeruginosa K-139 is a new source of fVIIa-sTF inhibitors. It also opens a new avenue for micropeptin K-139 and related depsipeptides as fVIIa-sTF inhibitors. Full article

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Open AccessArticle

Utilization of Fishery Processing By-Product Squid Pens for α-Glucosidase Inhibitors Production by Paenibacillus sp.

by Van Bon Nguyen, Anh Dzung Nguyen and San-Lang Wang

Mar. Drugs 2017, 15(9), 274; https://doi.org/10.3390/md15090274 - 30 Aug 2017

Cited by 39 | Viewed by 5340

Abstract

The supernatants (the solution part received after centrifugation) of squid pens fermented by four species of Paenibacillus showed potent inhibitory activity against α-glucosidases derived from yeast (79–98%) and rats (76–83%). The inhibition of acarbose—a commercial antidiabetic drug, used against yeast and rat α-glucosidases—was [...] Read more.

The supernatants (the solution part received after centrifugation) of squid pens fermented by four species of Paenibacillus showed potent inhibitory activity against α-glucosidases derived from yeast (79–98%) and rats (76–83%). The inhibition of acarbose—a commercial antidiabetic drug, used against yeast and rat α-glucosidases—was tested for comparison; it showed inhibitory activity of 64% and 88%, respectively. Other chitinolytic or proteolytic enzyme-producing bacterial strains were also used to ferment squid pens, but no inhibition activity was detected from the supernatants. Paenibacillus sp. TKU042, the most active α-glucosidase inhibitor (aGI)-producing strain, was selected to determine the optimal cultivation parameters. This bacterium achieved the highest aGI productivity (527 µg/mL) when 1% squid pens were used as the sole carbon/nitrogen source with a medium volume of 130 mL (initial pH 6.85) in a 250 mL flask (48% of air head space), at 30 °C for 3–4 d. The aGI productivity increased 3.1-fold after optimization of the culture conditions. Some valuable characteristics of Paenibacillus aGIs were also studied, including pH and thermal stability and specific inhibitory activity. These microbial aGIs showed efficient inhibition against α-glucosidases from rat, yeast, and bacteria, but weak inhibition against rice α-glucosidase with IC₅₀ values of 362, 252, 189, and 773 µg/mL, respectively. In particular, these aGIs showed highly stable activity over a large pH (2–13) and temperature range (40–100 °C). Various techniques, including: Diaoin, Octadecylsilane opened columns, and preparative HPLC coupled with testing bioactivity resulted in isolating a main active compound; this major inhibitor was identified as homogentisic acid (HGA). Notably, HGA was confirmed as a new inhibitor, a non-sugar-based aGI, and as possessing stronger activity than acarbose with IC_50, and maximum inhibition values of 220 μg/mL, 95%, and 1510 μg/mL, 65%, respectively. These results suggest that squid pens, an abundant and low-cost fishery processing by-product, constitute a viable source for the production of antidiabetic materials via fermentation by strains of Paenibacillus. This fermented product shows promising applications in diabetes or diabetes related to obesity treatment due to their stability, potent bioactivity, and efficient inhibition against mammalian enzymes. Full article

(This article belongs to the Special Issue Bioconversion of Marine Resources)

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Open AccessArticle

Ciguatoxins Evoke Potent CGRP Release by Activation of Voltage-Gated Sodium Channel Subtypes Na_V1.9, Na_V1.7 and Na_V1.1

by Filip Touska, Simon Sattler, Philipp Malsch, Richard J. Lewis, Peter W. Reeh and Katharina Zimmermann

Mar. Drugs 2017, 15(9), 269; https://doi.org/10.3390/md15090269 - 30 Aug 2017

Cited by 16 | Viewed by 5735

Abstract

Ciguatoxins (CTXs) are marine toxins that cause ciguatera fish poisoning, a debilitating disease dominated by sensory and neurological disturbances that include cold allodynia and various painful symptoms as well as long-lasting pruritus. Although CTXs are known as the most potent mammalian sodium channel [...] Read more.

Ciguatoxins (CTXs) are marine toxins that cause ciguatera fish poisoning, a debilitating disease dominated by sensory and neurological disturbances that include cold allodynia and various painful symptoms as well as long-lasting pruritus. Although CTXs are known as the most potent mammalian sodium channel activator toxins, the etiology of many of its neurosensory symptoms remains unresolved. We recently described that local application of 1 nM Pacific Ciguatoxin-1 (P-CTX-1) into the skin of human subjects induces a long-lasting, painful axon reflex flare and that CTXs are particularly effective in releasing calcitonin-gene related peptide (CGRP) from nerve terminals. In this study, we used mouse and rat skin preparations and enzyme-linked immunosorbent assays (ELISA) to study the molecular mechanism by which P-CTX-1 induces CGRP release. We show that P-CTX-1 induces CGRP release more effectively in mouse as compared to rat skin, exhibiting EC₅₀ concentrations in the low nanomolar range. P-CTX-1-induced CGRP release from skin is dependent on extracellular calcium and sodium, but independent from the activation of various thermosensory transient receptor potential (TRP) ion channels. In contrast, lidocaine and tetrodotoxin (TTX) reduce CGRP release by 53–75%, with the remaining fraction involving L-type and T-type voltage-gated calcium channels (VGCC). Using transgenic mice, we revealed that the TTX-resistant voltage-gated sodium channel (VGSC) Na_V1.9, but not Na_V1.8 or Na_V1.7 alone and the combined activation of the TTX-sensitive VGSC subtypes Na_V1.7 and Na_V1.1 carry the largest part of the P-CTX-1-caused CGRP release of 42% and 34%, respectively. Given the contribution of CGRP to nociceptive and itch sensing pathways, our findings contribute to a better understanding of sensory symptoms of acute and chronic ciguatera that may help in the identification of potential therapeutics. Full article

(This article belongs to the Special Issue Marine Drugs and Ion Currents)

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Open AccessFeature PaperReview

Marine Pharmacology in 2012–2013: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, and Antiviral Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action

by Alejandro M. S. Mayer, Abimael D. Rodríguez, Orazio Taglialatela-Scafati and Nobuhiro Fusetani

Mar. Drugs 2017, 15(9), 273; https://doi.org/10.3390/md15090273 - 29 Aug 2017

Cited by 75 | Viewed by 14601

Abstract

The peer-reviewed marine pharmacology literature from 2012 to 2013 was systematically reviewed, consistent with the 1998–2011 reviews of this series. Marine pharmacology research from 2012 to 2013, conducted by scientists from 42 countries in addition to the United States, reported findings on the [...] Read more.

The peer-reviewed marine pharmacology literature from 2012 to 2013 was systematically reviewed, consistent with the 1998–2011 reviews of this series. Marine pharmacology research from 2012 to 2013, conducted by scientists from 42 countries in addition to the United States, reported findings on the preclinical pharmacology of 257 marine compounds. The preclinical pharmacology of compounds isolated from marine organisms revealed antibacterial, antifungal, antiprotozoal, antituberculosis, antiviral and anthelmitic pharmacological activities for 113 marine natural products. In addition, 75 marine compounds were reported to have antidiabetic and anti-inflammatory activities and affect the immune and nervous system. Finally, 69 marine compounds were shown to display miscellaneous mechanisms of action which could contribute to novel pharmacological classes. Thus, in 2012–2013, the preclinical marine natural product pharmacology pipeline provided novel pharmacology and lead compounds to the clinical marine pharmaceutical pipeline, and contributed significantly to potentially novel therapeutic approaches to several global disease categories. Full article

(This article belongs to the Special Issue From Bioactive Compounds to New Drugs: Commemorative Issue Dedicated to Professor Ernesto Fattorusso (1937-2012))

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Open AccessReview

Current Status and Future Prospects of Marine Natural Products (MNPs) as Antimicrobials

by Alka Choudhary, Lynn M. Naughton, Itxaso Montánchez, Alan D. W. Dobson and Dilip K. Rai

Mar. Drugs 2017, 15(9), 272; https://doi.org/10.3390/md15090272 - 28 Aug 2017

Cited by 109 | Viewed by 15845

Abstract

The marine environment is a rich source of chemically diverse, biologically active natural products, and serves as an invaluable resource in the ongoing search for novel antimicrobial compounds. Recent advances in extraction and isolation techniques, and in state-of-the-art technologies involved in organic synthesis [...] Read more.

The marine environment is a rich source of chemically diverse, biologically active natural products, and serves as an invaluable resource in the ongoing search for novel antimicrobial compounds. Recent advances in extraction and isolation techniques, and in state-of-the-art technologies involved in organic synthesis and chemical structure elucidation, have accelerated the numbers of antimicrobial molecules originating from the ocean moving into clinical trials. The chemical diversity associated with these marine-derived molecules is immense, varying from simple linear peptides and fatty acids to complex alkaloids, terpenes and polyketides, etc. Such an array of structurally distinct molecules performs functionally diverse biological activities against many pathogenic bacteria and fungi, making marine-derived natural products valuable commodities, particularly in the current age of antimicrobial resistance. In this review, we have highlighted several marine-derived natural products (and their synthetic derivatives), which have gained recognition as effective antimicrobial agents over the past five years (2012–2017). These natural products have been categorized based on their chemical structures and the structure-activity mediated relationships of some of these bioactive molecules have been discussed. Finally, we have provided an insight into how genome mining efforts are likely to expedite the discovery of novel antimicrobial compounds. Full article

(This article belongs to the Special Issue Genome Mining and Marine Microbial Natural Products)

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1002 KiB

Open AccessArticle

Paulomycin G, a New Natural Product with Cytotoxic Activity against Tumor Cell Lines Produced by Deep-Sea Sediment Derived Micromonospora matsumotoense M-412 from the Avilés Canyon in the Cantabrian Sea

by Aida Sarmiento-Vizcaíno, Alfredo F. Braña, Ignacio Pérez-Victoria, Jesús Martín, Nuria De Pedro, Mercedes De la Cruz, Caridad Díaz, Francisca Vicente, José L. Acuña, Fernando Reyes, Luis A. García and Gloria Blanco

Mar. Drugs 2017, 15(9), 271; https://doi.org/10.3390/md15090271 - 28 Aug 2017

Cited by 46 | Viewed by 6448

Abstract

The present article describes a structurally novel natural product of the paulomycin family, designated as paulomycin G (1), obtained from the marine strain Micromonospora matsumotoense M-412, isolated from Cantabrian Sea sediments collected at 2000 m depth during an oceanographic expedition to [...] Read more.

The present article describes a structurally novel natural product of the paulomycin family, designated as paulomycin G (1), obtained from the marine strain Micromonospora matsumotoense M-412, isolated from Cantabrian Sea sediments collected at 2000 m depth during an oceanographic expedition to the submarine Avilés Canyon. Paulomycin G is structurally unique since—to our knowledge—it is the first member of the paulomycin family of antibiotics lacking the paulomycose moiety. It is also the smallest bioactive paulomycin reported. Its structure was determined using HRMS and 1D and 2D NMR spectroscopy. This novel natural product displays strong cytotoxic activities against different human tumour cell lines, such as pancreatic adenocarcinoma (MiaPaca_2), breast adenocarcinoma (MCF-7), and hepatocellular carcinoma (HepG2). The compound did not show any significant bioactivity when tested against a panel of bacterial and fungal pathogens. Full article

(This article belongs to the Collection Marine Compounds and Cancer)

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Open AccessArticle

Sequence Analysis, Kinetic Constants, and Anion Inhibition Profile of the Nacrein-Like Protein (CgiNAP2X1) from the Pacific Oyster Magallana gigas (Ex-Crassostrea gigas)

by Rosa Perfetto, Sonia Del Prete, Daniela Vullo, Giovanni Sansone, Carmela M. A. Barone, Mosè Rossi, Claudiu T. Supuran and Clemente Capasso

Mar. Drugs 2017, 15(9), 270; https://doi.org/10.3390/md15090270 - 28 Aug 2017

Cited by 3 | Viewed by 4287

Abstract

The carbonic anhydrase (CA, EC 4.2.1.1) superfamily of metalloenzymes catalyzes the hydration of carbon dioxide to bicarbonate and protons. The catalytically active form of these enzymes incorporates a metal hydroxide derivative, the formation of which is the rate-determining step of catalytic reaction, being [...] Read more.

The carbonic anhydrase (CA, EC 4.2.1.1) superfamily of metalloenzymes catalyzes the hydration of carbon dioxide to bicarbonate and protons. The catalytically active form of these enzymes incorporates a metal hydroxide derivative, the formation of which is the rate-determining step of catalytic reaction, being affected by the transfer of a proton from a metal-coordinated water molecule to the environment. Here, we report the cloning, expression, and purification of a particular CA, i.e., nacrein-like protein encoded in the genome of the Pacific oyster Magallana gigas (previously known as Crassostrea gigas). Furthermore, the amino acid sequence, kinetic constants, and anion inhibition profile of the recombinant enzyme were investigated for the first time. The new protein, CgiNAP2X1, is highly effective as catalyst for the CO₂ hydration reaction, based on the measured kinetic parameters, i.e., k_cat = 1.0 × 10⁶ s⁻¹ and k_cat/K_M = 1.2 × 10⁸ M⁻¹·s⁻¹. CgiNAP2X1 has a putative signal peptide, which probably allows an extracellular localization of the protein. The inhibition data demonstrated that the best anion inhibitors of CgiNAP2X1 were diethyldithiocarbamate, sulfamide, sulfamate, phenylboronic acid and phenylarsonic acid, which showed a micromolar affinity for this enzyme, with K_Is in the range of 76–87 μM. These studies may add new information on the physiological role of the molluskan CAs in the biocalcification processes. Full article

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Open AccessArticle

New Marine Antifouling Compounds from the Red Alga Laurencia sp.

by Yuko Oguri, Mami Watanabe, Takafumi Ishikawa, Takashi Kamada, Charles S. Vairappan, Hiroshi Matsuura, Kensuke Kaneko, Takahiro Ishii, Minoru Suzuki, Erina Yoshimura, Yasuyuki Nogata and Tatsufumi Okino

Mar. Drugs 2017, 15(9), 267; https://doi.org/10.3390/md15090267 - 28 Aug 2017

Cited by 28 | Viewed by 6237

Abstract

Six new compounds, omaezol, intricatriol, hachijojimallenes A and B, debromoaplysinal, and 11,12-dihydro-3-hydroxyretinol have been isolated from four collections of Laurencia sp. These structures were determined by MS and NMR analyses. Their antifouling activities were evaluated together with eight previously known compounds isolated from [...] Read more.

Six new compounds, omaezol, intricatriol, hachijojimallenes A and B, debromoaplysinal, and 11,12-dihydro-3-hydroxyretinol have been isolated from four collections of Laurencia sp. These structures were determined by MS and NMR analyses. Their antifouling activities were evaluated together with eight previously known compounds isolated from the same samples. In particular, omaezol and hachijojimallene A showed potent activities (EC₅₀ = 0.15–0.23 µg/mL) against larvae of the barnacle Amphibalanus amphitrite. Full article

(This article belongs to the Special Issue Antifouling Marine Natural Products)

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Open AccessReview

Mini-Review: Antifouling Natural Products from Marine Microorganisms and Their Synthetic Analogs

by Kai-Ling Wang, Ze-Hong Wu, Yu Wang, Chang-Yun Wang and Ying Xu

Mar. Drugs 2017, 15(9), 266; https://doi.org/10.3390/md15090266 - 28 Aug 2017

Cited by 79 | Viewed by 7793

Abstract

Biofouling causes huge economic loss and generates serious ecological issues worldwide. Marine coatings incorporated with antifouling (AF) compounds are the most common practices to prevent biofouling. With a ban of organotins and an increase in the restrictions regarding the use of other AF [...] Read more.

Biofouling causes huge economic loss and generates serious ecological issues worldwide. Marine coatings incorporated with antifouling (AF) compounds are the most common practices to prevent biofouling. With a ban of organotins and an increase in the restrictions regarding the use of other AF alternatives, exploring effective and environmentally friendly AF compounds has become an urgent demand for marine coating industries. Marine microorganisms, which have the largest biodiversity, represent a rich and important source of bioactive compounds and have many medical and industrial applications. This review summarizes 89 natural products from marine microorganisms and 13 of their synthetic analogs with AF EC₅₀ values ≤ 25 μg/mL from 1995 (the first report about marine microorganism-derived AF compounds) to April 2017. Some compounds with the EC₅₀ values < 5 μg/mL and LC₅₀/EC₅₀ ratios > 50 are highlighted as potential AF compounds, and the preliminary analysis of structure-relationship (SAR) of these compounds is also discussed briefly. In the last part, current challenges and future research perspectives are proposed based on opinions from many previous reviews. To provide clear guidance for the readers, the AF compounds from microorganisms and their synthetic analogs in this review are categorized into ten types, including fatty acids, lactones, terpenes, steroids, benzenoids, phenyl ethers, polyketides, alkaloids, nucleosides and peptides. In addition to the major AF compounds which targets macro-foulers, this review also includes compounds with antibiofilm activity since micro-foulers also contribute significantly to the biofouling communities. Full article

(This article belongs to the Special Issue Antifouling Marine Natural Products)

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Open AccessReview

Antifouling Compounds from Marine Macroalgae

by Hans Uwe Dahms and Sergey Dobretsov

Mar. Drugs 2017, 15(9), 265; https://doi.org/10.3390/md15090265 - 28 Aug 2017

Cited by 89 | Viewed by 10423

Abstract

Marine macroalgae produce a wide variety of biologically-active metabolites that have been developed into commercial products, such as antibiotics, immunosuppressive, anti-inflammatory, cytotoxic agents, and cosmetic products. Many marine algae remain clean over longer periods of time, suggesting their strong antifouling potential. Isolation of [...] Read more.

Marine macroalgae produce a wide variety of biologically-active metabolites that have been developed into commercial products, such as antibiotics, immunosuppressive, anti-inflammatory, cytotoxic agents, and cosmetic products. Many marine algae remain clean over longer periods of time, suggesting their strong antifouling potential. Isolation of biogenic compounds and the determination of their structure could provide leads for the development of environmentally-friendly antifouling paints. Isolated substances with potent antifouling activity belong to fatty acids, lipopeptides, amides, alkaloids, lactones, steroids, terpenoids, and pyrroles. It is unclear as yet to what extent symbiotic microorganisms are involved in the synthesis of these compounds. Algal secondary metabolites have the potential to be produced commercially using genetic and metabolic engineering techniques. This review provides an overview of publications from 2010 to February 2017 about antifouling activity of green, brown, and red algae. Some researchers were focusing on antifouling compounds of brown macroalgae, while metabolites of green algae received less attention. Several studies tested antifouling activity against bacteria, microalgae and invertebrates, but in only a few studies was the quorum sensing inhibitory activity of marine macroalgae tested. Rarely, antifouling compounds from macroalgae were isolated and tested in an ecologically-relevant way. Full article

(This article belongs to the Special Issue Antifouling Marine Natural Products)

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Open AccessReview

Review on Molecular Mechanisms of Antifouling Compounds: An Update since 2012

by Lianguo Chen and Pei-Yuan Qian

Mar. Drugs 2017, 15(9), 264; https://doi.org/10.3390/md15090264 - 28 Aug 2017

Cited by 73 | Viewed by 6699

Abstract

Better understanding of the mechanisms of antifouling compounds is recognized to be of high value in establishing sensitive biomarkers, allowing the targeted optimization of antifouling compounds and guaranteeing environmental safety. Despite vigorous efforts to find new antifouling compounds, information about the mechanisms of [...] Read more.

Better understanding of the mechanisms of antifouling compounds is recognized to be of high value in establishing sensitive biomarkers, allowing the targeted optimization of antifouling compounds and guaranteeing environmental safety. Despite vigorous efforts to find new antifouling compounds, information about the mechanisms of antifouling is still scarce. This review summarizes the progress into understanding the molecular mechanisms underlying antifouling activity since 2012. Non-toxic mechanisms aimed at specific targets, including inhibitors of transmembrane transport, quorum sensing inhibitors, neurotransmission blockers, adhesive production/release inhibitors and enzyme/protein inhibitors, are put forward for natural antifouling products or shelf-stable chemicals. Several molecular targets show good potential for use as biomarkers in future mechanistic screening, such as acetylcholine esterase for neurotransmission, phenoloxidase/tyrosinase for the formation of adhesive plaques, N-acyl homoserine lactone for quorum sensing and intracellular Ca²⁺ levels as second messenger. The studies on overall responses to challenges by antifoulants can be categorized as general targets, including protein expression/metabolic activity regulators, oxidative stress inducers, neurotransmission blockers, surface modifiers, biofilm inhibitors, adhesive production/release inhibitors and toxic killing. Given the current situation and the knowledge gaps regarding the development of alternative antifoulants, a basic workflow is proposed that covers the indispensable steps, including preliminary mechanism- or bioassay-guided screening, evaluation of environmental risks, field antifouling performance, clarification of antifouling mechanisms and the establishment of sensitive biomarkers, which are combined to construct a positive feedback loop. Full article

(This article belongs to the Special Issue Antifouling Marine Natural Products)

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