Marine Drugs

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Open AccessArticle

Aniquinazolines A–D, Four New Quinazolinone Alkaloids from Marine-Derived Endophytic Fungus Aspergillus nidulans

by Chun-Yan An, Xiao-Ming Li, Chun-Shun Li, Ming-Hui Wang, Gang-Ming Xu and Bin-Gui Wang

Mar. Drugs 2013, 11(7), 2682-2694; https://doi.org/10.3390/md11072682 - 23 Jul 2013

Cited by 49 | Viewed by 7939

Four new quinazolinone alkaloids, namely, aniquinazolines A–D (1–4), were isolated and identified from the culture of Aspergillus nidulans MA-143, an endophytic fungus obtained from the leaves of marine mangrove plant Rhizophora stylosa. The structures of the new compounds [...] Read more.

Four new quinazolinone alkaloids, namely, aniquinazolines A–D (1–4), were isolated and identified from the culture of Aspergillus nidulans MA-143, an endophytic fungus obtained from the leaves of marine mangrove plant Rhizophora stylosa. The structures of the new compounds were elucidated by spectroscopic analysis, and their absolute configurations were determined on the basis of chiral HPLC analysis of the acidic hydrolysates. The structure for 1 was confirmed by single-crystal X-ray diffraction analysis. All these compounds were examined for antibacterial and cytotoxic activity as well as brine shrimp (Artemia salina) lethality. Full article

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Open AccessArticle

Production, Characterization, and Antioxidant Activity of Fucoxanthin from the Marine Diatom Odontella aurita

by Song Xia, Ke Wang, Linglin Wan, Aifen Li, Qiang Hu and Chengwu Zhang

Mar. Drugs 2013, 11(7), 2667-2681; https://doi.org/10.3390/md11072667 - 23 Jul 2013

Cited by 330 | Viewed by 22247

Abstract

The production, characterization, and antioxidant capacity of the carotenoid fucoxanthin from the marine diatom Odontella aurita were investigated. The results showed that low light and nitrogen-replete culture medium enhanced the biosynthesis of fucoxanthin. The maximum biomass concentration of 6.36 g L⁻¹ and [...] Read more.

The production, characterization, and antioxidant capacity of the carotenoid fucoxanthin from the marine diatom Odontella aurita were investigated. The results showed that low light and nitrogen-replete culture medium enhanced the biosynthesis of fucoxanthin. The maximum biomass concentration of 6.36 g L⁻¹ and maximum fucoxanthin concentration of 18.47 mg g⁻¹ were obtained in cultures grown in a bubble column photobioreactor (Ø 3.0 cm inner diameter), resulting in a fucoxanthin volumetric productivity of 7.96 mg L⁻¹ day⁻¹. A slight reduction in biomass production was observed in the scaling up of O. aurita culture in a flat plate photobioreactor, yet yielded a comparable fucoxanthin volumetric productivity. A rapid method was developed for extraction and purification of fucoxanthin. The purified fucoxanthin was identified as all-trans-fucoxanthin, which exhibited strong antioxidant properties, with the effective concentration for 50% scavenging (EC₅₀) of 1,1-dihpenyl-2-picrylhydrazyl (DPPH) radical and 2,2′-Azino-bis(3-ethylbenzthiazoline-6-sulfonic acid (ABTS) radical being 0.14 and 0.03 mg mL⁻¹, respectively. Our results suggested that O. aurita can be a natural source of fucoxanthin for human health and nutrition. Full article

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

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Open AccessArticle

Antioxidant and Anti-Inflammatory Activities of Barettin

by Karianne F. Lind, Espen Hansen, Bjarne Østerud, Karl-Erik Eilertsen, Annette Bayer, Magnus Engqvist, Kinga Leszczak, Trond Ø. Jørgensen and Jeanette H. Andersen

Mar. Drugs 2013, 11(7), 2655-2666; https://doi.org/10.3390/md11072655 - 22 Jul 2013

Cited by 51 | Viewed by 10923

Abstract

In this paper, we present novel bioactivity for barettin isolated from the marine sponge Geodia barretti. We found that barettin showed strong antioxidant activity in biochemical assays as well as in a lipid peroxidation cell assay. A de-brominated synthetic analogue of barettin [...] Read more.

In this paper, we present novel bioactivity for barettin isolated from the marine sponge Geodia barretti. We found that barettin showed strong antioxidant activity in biochemical assays as well as in a lipid peroxidation cell assay. A de-brominated synthetic analogue of barettin did not show the same activity in the antioxidant cell assay, indicating that bromine is important for cellular activity. Barettin was also able to inhibit the secretion of the inflammatory cytokines IL-1β and TNFα from LPS-stimulated THP-1 cells. This combination of anti-inflammatory and antioxidant activities could indicate that barettin has an atheroprotective effect and may therefore be an interesting product to prevent development of atherosclerosis. Full article

(This article belongs to the Special Issue Bioactive Compound from Marine Sponges)

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Open AccessArticle

Occurrence of the Microcystins MC-LW and MC-LF in Dutch Surface Waters and Their Contribution to Total Microcystin Toxicity

by Elisabeth J. Faassen and Miquel Lürling

Mar. Drugs 2013, 11(7), 2643-2654; https://doi.org/10.3390/md11072643 - 22 Jul 2013

Cited by 56 | Viewed by 9503

Abstract

Microcystins (MCs) are the most frequently found cyanobacterial toxins in freshwater systems. Many MC variants have been identified and variants differ in their toxicity. Recent studies showed that the variants MC-LW and MC-LF might be more toxic than MC-LR, the variant that is [...] Read more.

Microcystins (MCs) are the most frequently found cyanobacterial toxins in freshwater systems. Many MC variants have been identified and variants differ in their toxicity. Recent studies showed that the variants MC-LW and MC-LF might be more toxic than MC-LR, the variant that is most abundant and mostly used for risk assessments. As little is known about the presence of these two variants in The Netherlands, we determined their occurrence by analyzing 88 water samples and 10 scum samples for eight MC variants ((dm-7-)MC-RR, MC-YR, (dm-7-)MC-LR, MC-LY, MC-LW and MC-LF) by liquid chromatography with tandem mass spectrometry detection. All analyzed MC variants were detected, and MC-LW and/or MC-LF were present in 32% of the MC containing water samples. When MC-LW and MC-LF were present, they contributed to nearly 10% of the total MC concentrations, but due to their suspected high toxicity, their average contribution to the total MC toxicity was estimated to be at least 45%. Given the frequent occurrence and possible high toxicity of MC-LW and MC-LF, it seems better to base health risk assessments on the toxicity contributions of different MC variants than on MC-LR concentrations alone. Full article

(This article belongs to the Special Issue Compounds from Cyanobacteria)

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Open AccessArticle

Proteomic Investigation of the Sinulariolide-Treated Melanoma Cells A375: Effects on the Cell Apoptosis through Mitochondrial-Related Pathway and Activation of Caspase Cascade

by Hsing-Hui Li, Jui-Hsin Su, Chien-Chih Chiu, Jen-Jie Lin, Zih-Yan Yang, Wen-Ing Hwang, Yu-Kuei Chen, Yu-Hsuan Lo and Yu-Jen Wu

Mar. Drugs 2013, 11(7), 2625-2642; https://doi.org/10.3390/md11072625 - 22 Jul 2013

Cited by 42 | Viewed by 10425

Abstract

Sinulariolide is an active compound isolated from the cultured soft coral Sinularia flexibilis. In this study, we investigated the effects of sinulariolide on A375 melanoma cell growth and protein expression. Sinulariolide suppressed the proliferation and migration of melanoma cells in a concentration-dependent [...] Read more.

Sinulariolide is an active compound isolated from the cultured soft coral Sinularia flexibilis. In this study, we investigated the effects of sinulariolide on A375 melanoma cell growth and protein expression. Sinulariolide suppressed the proliferation and migration of melanoma cells in a concentration-dependent manner and was found to induce both early and late apoptosis by flow cytometric analysis. Comparative proteomic analysis was conducted to investigate the effects of sinulariolide at the molecular level by comparison between the protein profiles of melanoma cells treated with sinulariolide and those without treatment. Two-dimensional gel electrophoresis (2-DE) master maps of control and treated A375 cells were generated by analysis with PDQuest software. Comparison between these maps showed up- and downregulation of 21 proteins, seven of which were upregulated and 14 were downregulated. The proteomics studies described here identify some proteins that are involved in mitochondrial dysfunction and apoptosis-associated proteins, including heat shock protein 60, heat shock protein beta-1, ubiquinol cytochrome c reductase complex core protein 1, isocitrate dehydrogenase (NAD) subunit alpha (down-regulated), and prohibitin (up-regulated), in A375 melanoma cells exposed to sinulariolide. Sinulariolide-induced apoptosis is relevant to mitochondrial-mediated apoptosis via caspase-dependent pathways, elucidated by the loss of mitochondrial membrane potential, release of cytochrome c, and activation of Bax, Bad and caspase-3/-9, as well as suppression of p-Bad, Bcl-xL and Bcl-2. Taken together, our results show that sinulariolide-induced apoptosis might be related to activation of the caspase cascade and mitochondria dysfunction pathways. Our results suggest that sinulariolide merits further evaluation as a chemotherapeutic agent for human melanoma. Full article

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

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Open AccessArticle

Secondary Metabolites of a Mangrove Endophytic Fungus Aspergillus terreus (No. GX7-3B) from the South China Sea

by Chun-Mei Deng, Shi-Xin Liu, Cai-Huan Huang, Ji-Yan Pang and Yong-Cheng Lin

Mar. Drugs 2013, 11(7), 2616-2624; https://doi.org/10.3390/md11072616 - 19 Jul 2013

Cited by 67 | Viewed by 8746

Abstract

The mangrove endophytic fungus Aspergillus terreus (No. GX7-3B) was cultivated in potato dextrose liquid medium, and one rare thiophene compound (1), together with anhydrojavanicin (2), 8-O-methylbostrycoidin (3), 8-O-methyljavanicin (4), botryosphaerone D [...] Read more.

The mangrove endophytic fungus Aspergillus terreus (No. GX7-3B) was cultivated in potato dextrose liquid medium, and one rare thiophene compound (1), together with anhydrojavanicin (2), 8-O-methylbostrycoidin (3), 8-O-methyljavanicin (4), botryosphaerone D (5), 6-ethyl-5-hydroxy-3,7-dimethoxynaphthoquinone (6), 3β,5α-dihydroxy-(22E,24R)-ergosta-7,22-dien-6-one (7), 3β,5α,14α-trihydroxy-(22E,24R)-ergosta-7, 22-dien-6-one (8), NGA0187 (9) and beauvericin (10), were isolated. Their structures were elucidated by analysis of spectroscopic data. This is the first report of a natural origin for compound 6. Moreover, compounds 3, 4, 5, 7, 8 and 10 were obtained from marine microorganism for the first time. In the bioactive assays in vitro, compounds 2, 3, 9 and 10 displayed remarkable inhibiting actions against α-acetylcholinesterase (AChE) with IC₅₀ values 2.01, 6.71, 1.89, and 3.09 μM, respectively. Furthermore, in the cytotoxicity assays, compounds 7 and 10 exhibited strong or moderate cytotoxic activities against MCF-7, A549, Hela and KB cell lines with IC₅₀ values 4.98 and 2.02 (MCF-7), 1.95 and 0.82 (A549), 0.68 and 1.14 (Hela), and 1.50 and 1.10 μM (KB), respectively; compound 8 had weak inhibitory activities against these tumor cell lines; compounds 1, 2, 3, 4, 5, 6 and 9 exhibited no inhibitory activities against them. Full article

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Open AccessArticle

Lithothamnion muelleri Controls Inflammatory Responses, Target Organ Injury and Lethality Associated with Graft-versus-Host Disease in Mice

by Barbara M. Rezende, Priscila T. T. Bernardes, Carolina B. Resende, Rosa M. E. Arantes, Danielle G. Souza, Fernão C. Braga, Marina G. M. Castor, Mauro M. Teixeira and Vanessa Pinho

Mar. Drugs 2013, 11(7), 2595-2615; https://doi.org/10.3390/md11072595 - 18 Jul 2013

Cited by 14 | Viewed by 7301

Abstract

Lithothamnion muelleri (Hapalidiaceae) is a marine red alga, which is a member of a group of algae with anti-inflammatory, antitumor, and immunomodulatory properties. The present study evaluated the effects of treatment with Lithothamnion muelleri extract (LM) in a model of acute graft-versus [...] Read more.

Lithothamnion muelleri (Hapalidiaceae) is a marine red alga, which is a member of a group of algae with anti-inflammatory, antitumor, and immunomodulatory properties. The present study evaluated the effects of treatment with Lithothamnion muelleri extract (LM) in a model of acute graft-versus-host disease (GVHD), using a model of adoptive splenocyte transfer from C57BL/6 donors into B6D2F1 recipient mice. Mice treated with LM showed reduced clinical signs of disease and mortality when compared with untreated mice. LM-treated mice had reduced tissue injury, less bacterial translocation, and decreased levels of proinflammatory cytokines and chemokines (interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), chemokine (C-C motif) ligand 2 (CCL2), chemokine (C-C motif) ligand 3 (CCL3) and chemokine (C-C motif) ligand 5 (CCL5)). The polysaccharide-rich fraction derived from LM could inhibit leukocyte rolling and adhesion in intestinal venules, as assessed by intravital microscopy. LM treatment did not impair the beneficial effects of graft-versus-leukaemia (GVL). Altogether, our studies suggest that treatment with Lithothamnion muelleri has a potential therapeutic application in GVHD treatment. Full article

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

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Open AccessArticle

APS8, a Polymeric Alkylpyridinium Salt Blocks α7 nAChR and Induces Apoptosis in Non-Small Cell Lung Carcinoma

by Ana Zovko, Kristina Viktorsson, Rolf Lewensohn, Katja Kološa, Metka Filipič, Hong Xing, William R. Kem, Laura Paleari and Tom Turk

Mar. Drugs 2013, 11(7), 2574-2594; https://doi.org/10.3390/md11072574 - 16 Jul 2013

Cited by 27 | Viewed by 8316

Abstract

Naturally occurring 3-alkylpyridinium polymers (poly-APS) from the marine sponge Reniera sarai, consisting of monomers containing polar pyridinium and nonpolar alkyl chain moieties, have been demonstrated to exert a wide range of biological activities, including a selective cytotoxicity against non-small cell lung cancer [...] Read more.

Naturally occurring 3-alkylpyridinium polymers (poly-APS) from the marine sponge Reniera sarai, consisting of monomers containing polar pyridinium and nonpolar alkyl chain moieties, have been demonstrated to exert a wide range of biological activities, including a selective cytotoxicity against non-small cell lung cancer (NSCLC) cells. APS8, an analog of poly-APS with defined alkyl chain length and molecular size, non-competitively inhibits α7 nicotinic acetylcholine receptors (nAChRs) at nanomolar concentrations that are too low to be acetylcholinesterase (AChE) inhibitory or generally cytotoxic. In the present study we show that APS8 inhibits NSCLC tumor cell growth and activates apoptotic pathways. APS8 was not toxic for normal lung fibroblasts. Furthermore, in NSCLC cells, APS8 reduced the adverse anti-apoptotic, proliferative effects of nicotine. Our results suggest that APS8 or similar compounds might be considered as lead compounds to develop antitumor therapeutic agents for at least certain types of lung cancer. Full article

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

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Open AccessReview

Marine Pharmacology in 2009–2011: 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 2013, 11(7), 2510-2573; https://doi.org/10.3390/md11072510 - 16 Jul 2013

Cited by 271 | Viewed by 22125

Abstract

The peer-reviewed marine pharmacology literature from 2009 to 2011 is presented in this review, following the format used in the 1998–2008 reviews of this series. The pharmacology of structurally-characterized compounds isolated from marine animals, algae, fungi and bacteria is discussed in a comprehensive [...] Read more.

The peer-reviewed marine pharmacology literature from 2009 to 2011 is presented in this review, following the format used in the 1998–2008 reviews of this series. The pharmacology of structurally-characterized compounds isolated from marine animals, algae, fungi and bacteria is discussed in a comprehensive manner. Antibacterial, antifungal, antiprotozoal, antituberculosis, and antiviral pharmacological activities were reported for 102 marine natural products. Additionally, 60 marine compounds were observed to affect the immune and nervous system as well as possess antidiabetic and anti-inflammatory effects. Finally, 68 marine metabolites were shown to interact with a variety of receptors and molecular targets, and thus will probably contribute to multiple pharmacological classes upon further mechanism of action studies. Marine pharmacology during 2009–2011 remained a global enterprise, with researchers from 35 countries, and the United States, contributing to the preclinical pharmacology of 262 marine compounds which are part of the preclinical pharmaceutical pipeline. Continued pharmacological research with marine natural products will contribute to enhance the marine pharmaceutical clinical pipeline, which in 2013 consisted of 17 marine natural products, analogs or derivatives targeting a limited number of disease categories. Full article

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Open AccessArticle

Parathyrsoidins A–D, Four New Sesquiterpenoids from the Soft Coral Paralemnalia thyrsoides

by Yen-Ju Tseng, Yu-Sheng Lee, Shang-Kwei Wang, Jyh-Horng Sheu and Chang-Yih Duh

Mar. Drugs 2013, 11(7), 2501-2509; https://doi.org/10.3390/md11072501 - 15 Jul 2013

Cited by 18 | Viewed by 6102

Abstract

Four new nardosinane-type sesquiterpenoids, parathyrsoidins A–D (1–4) were isolated from the soft coral Paralemnalia thyrsoides. The structures of parathyrsoidins A–D (1–4) were determined by extensive spectral analysis and their cytotoxicity against selected cancer cell [...] Read more.

Four new nardosinane-type sesquiterpenoids, parathyrsoidins A–D (1–4) were isolated from the soft coral Paralemnalia thyrsoides. The structures of parathyrsoidins A–D (1–4) were determined by extensive spectral analysis and their cytotoxicity against selected cancer cell lines as well as antiviral activity against human cytomegalovirus (HCMV) were evaluated in vitro. Full article

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Open AccessArticle

Effect of Grazing-Mediated Dimethyl Sulfide (DMS) Production on the Swimming Behavior of the Copepod Calanus helgolandicus

by Mark N. Breckels, Nikolai W. F. Bode, Edward A. Codling and Michael Steinke

Mar. Drugs 2013, 11(7), 2486-2500; https://doi.org/10.3390/md11072486 - 15 Jul 2013

Cited by 16 | Viewed by 8055

Abstract

Chemical interactions play a fundamental role in the ecology of marine foodwebs. Dimethyl sulfide (DMS) is a ubiquitous marine trace gas that acts as a bioactive compound by eliciting foraging behavior in a range of marine taxa including the copepod Temora longicornis. [...] Read more.

Chemical interactions play a fundamental role in the ecology of marine foodwebs. Dimethyl sulfide (DMS) is a ubiquitous marine trace gas that acts as a bioactive compound by eliciting foraging behavior in a range of marine taxa including the copepod Temora longicornis. Production of DMS can rapidly increase following microzooplankton grazing on phytoplankton. Here, we investigated whether grazing-induced DMS elicits an increase in foraging behavior in the copepod Calanus helgolandicus. We developed a semi-automated method to quantify the effect of grazing-mediated DMS on the proportion of the time budget tethered females allocate towards slow swimming, typically associated with feeding. The pooled data showed no differences in the proportion of the 25 min time budget allocated towards slow swimming between high (23.6 ± 9.74%) and low (29.1 ± 18.33%) DMS treatments. However, there was a high degree of variability between behavioral responses of individual copepods. We discuss the need for more detailed species-specific studies of individual level responses of copepods to chemical signals at different spatial scales to improve our understanding of chemical interactions between copepods and their prey. Full article

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

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Open AccessArticle

Antimetastatic Effect of Halichondramide, a Trisoxazole Macrolide from the Marine Sponge Chondrosia corticata, on Human Prostate Cancer Cells via Modulation of Epithelial-to-Mesenchymal Transition

by Yoonho Shin, Gi Dae Kim, Ju-eun Jeon, Jongheon Shin and Sang Kook Lee

Mar. Drugs 2013, 11(7), 2472-2485; https://doi.org/10.3390/md11072472 - 15 Jul 2013

Cited by 30 | Viewed by 7731

Abstract

Halichondramide (HCA), a trisoxazole-containing macrolide isolated from the marine sponge Chondrosia corticata has been shown to exhibit cytotoxicity and antifungal activities. In our previous study, HCA was also found to exhibit antiproliferative activity against a variety of cancer cells. However, the precise mechanism [...] Read more.

Halichondramide (HCA), a trisoxazole-containing macrolide isolated from the marine sponge Chondrosia corticata has been shown to exhibit cytotoxicity and antifungal activities. In our previous study, HCA was also found to exhibit antiproliferative activity against a variety of cancer cells. However, the precise mechanism of action of HCA in the antitumor activity remains to be elucidated. In the present study, we identified the antimetastatic activity of HCA in the highly metastatic PC3 human prostate cancer cells. HCA showed potent growth inhibitory activity of the PC3 cells with an IC₅₀ value of 0.81 µM. Further analysis revealed that HCA suppressed the expression of a potential metastatic biomarker, phosphatase of regenerating liver-3 (PRL-3), in PC3 cells. The suppression of PRL-3 by HCA sequentially down-regulates the expression of phosphoinositide 3-kinase (PI3K) subunits p85 and p110. The antimetastatic effect of HCA was also correlated with the down-regulation of matrix metalloproteases (MMPs) and the modulation of cadherin switches N-cadherin and E-cadherin. In addition, HCA also effectively suppressed the migration and invasion of PC3 cells. These findings suggest that halichondramide might serve as a potential inhibitor of tumor cell metastasis with the modulation of PRL-3. Full article

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Open AccessArticle

Bioactive Compounds Offered in Microcapsules to Determine the Nutritional Value of Copepods’ Natural Diet

by Dörthe C. Müller-Navarra and Mark E. Huntley

Mar. Drugs 2013, 11(7), 2459-2471; https://doi.org/10.3390/md11072459 - 12 Jul 2013

Cited by 2 | Viewed by 6241

Abstract

Experiments were performed, feeding Calanus pacificus seston and a food consisting of seston and microcapsules (μ-caps), i.e., protein and lipid μ-caps to test for potential biochemical limitation. Seston was collected off Scripps Pier (La Jolla, CA, USA). Whereas protein μ-caps were too [...] Read more.

Experiments were performed, feeding Calanus pacificus seston and a food consisting of seston and microcapsules (μ-caps), i.e., protein and lipid μ-caps to test for potential biochemical limitation. Seston was collected off Scripps Pier (La Jolla, CA, USA). Whereas protein μ-caps were too small to be efficiently ingested, lipid μ-caps rich in ω3-highly-unsaturated fatty acids (ω3-HUFA) were ingested similarly to natural seston and lipids were assimilated. However, egg production experiments exhibited that animals fed with lipid μ-caps didn’t produce significantly more eggs than with seston of equal carbon concentration and egg production even declined when the diet consisted of 50% lipid μ-caps. Thus, the content of certain ω3-HUFA seemed to have been sufficiently high in seston to prevent limitation. Algal counts revealed that seston consisted mainly of plankton rich in those fatty acids, such as cryptophytes, dinoflagellates, diatoms, and ciliates in the edible size range. This might be characteristic for upwelling systems like the area off Southern California which are known for high trophic transfer efficiency. Full article

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

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Open AccessArticle

Influence of Fucoidans on Hemostatic System

by Nadezhda E. Ustyuzhanina, Natalia A. Ushakova, Ksenia A. Zyuzina, Maria I. Bilan, Anna L. Elizarova, Oksana V. Somonova, Albina V. Madzhuga, Vadim B. Krylov, Marina E. Preobrazhenskaya, Anatolii I. Usov, Mikhail V. Kiselevskiy and Nikolay E. Nifantiev

Mar. Drugs 2013, 11(7), 2444-2458; https://doi.org/10.3390/md11072444 - 12 Jul 2013

Cited by 71 | Viewed by 8490

Abstract

Three structurally different fucoidans from the brown seaweeds Saccharina latissima (SL), Fucus vesiculosus (FV), and Cladosiphon okamuranus (CO), two chemically modified fucoidans with a higher degree of sulfation (SL-S, CO-S), and a synthetic totally sulfated octasaccharide (OS), related to fucoidans, were assessed on [...] Read more.

Three structurally different fucoidans from the brown seaweeds Saccharina latissima (SL), Fucus vesiculosus (FV), and Cladosiphon okamuranus (CO), two chemically modified fucoidans with a higher degree of sulfation (SL-S, CO-S), and a synthetic totally sulfated octasaccharide (OS), related to fucoidans, were assessed on anticoagulant and antithrombotic activities in different in vitro experiments. The effects were shown to depend on the structural features of the compounds tested. Native fucoidan SL with a degree of sulfation (DS) of 1.3 was found to be the most active sample, fucoidan FV (DS 0.9) demonstrated moderate activity, while the polysaccharide CO (DS 0.4) was inactive in all performed experiments, even at high concentrations. Additional introduction of sulfate groups into fucoidan SL slightly decreased the anticoagulant effect of SL-S, while sulfation of CO, giving rise to the preparation CO-S, increased the activity dramatically. The high level of anticoagulant activity of polysaccharides SL, SL-S, and CO-S was explained by their ability to form ternary complexes with ATIII-Xa and ATIII-IIa, as well as to bind directly to thrombin. Synthetic per-O-sulfated octasaccharide OS showed moderate anticoagulant effect, determined mainly by the interaction of OS with the factor Xa in the presence of ATIII. Comparable tendencies were observed in the antithrombotic properties of the compounds tested. Full article

(This article belongs to the Special Issue Selected Papers from the 1st Symposium on Marine Enzymes and Polysaccharides)

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Open AccessArticle

Structure of Fucoidan from Brown Seaweed Turbinaria ornata as Studied by Electrospray Ionization Mass Spectrometry (ESIMS) and Small Angle X-ray Scattering (SAXS) Techniques

by Thuy Thi Thu Thanh, Van Thi Thanh Tran, Yoshiaki Yuguchi, Ly Minh Bui and Tai Tien Nguyen

Mar. Drugs 2013, 11(7), 2431-2443; https://doi.org/10.3390/md11072431 - 12 Jul 2013

Cited by 32 | Viewed by 9978

Abstract

The purpose of this study is to elucidate both the chemical and conformational structure of an unfractionated fucoidan extracted from brown seaweed Turbinaria ornata collected at Nha-trang bay, Vietnam. Electrospray ionization mass spectrometry (ESI-MS) was used for determining the chemical structure and small [...] Read more.

The purpose of this study is to elucidate both the chemical and conformational structure of an unfractionated fucoidan extracted from brown seaweed Turbinaria ornata collected at Nha-trang bay, Vietnam. Electrospray ionization mass spectrometry (ESI-MS) was used for determining the chemical structure and small angle X-ray scattering (SAXS) provided conformational of the structure at the molecular level. The results showed that the fucoidan has a sulfate content of 25.6% and is mainly composed of fucose and galactose residues (Fuc:Gal ≈ 3:1). ESIMS analysis suggested that the fucoidan has a backbone of 3-linked α-l-Fucp residues with branches, →4)-Galp(1→ at C-4 of the fucan chain. Sulfate groups are attached mostly at C-2 and sometimes at C-4 of both fucose and galactose residues. A molecular model of the fucoidan was built based on obtained chemical structure and scattering curves estimated from molecular model and observed SAXS measurement were fitted. The results indicated that fucoidan under study has a rod-like bulky chain conformation. Full article

(This article belongs to the Special Issue Selected Papers from the 1st Symposium on Marine Enzymes and Polysaccharides)

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Open AccessArticle

Hydrolysis of Fucoidan by Fucoidanase Isolated from the Marine Bacterium, Formosa algae

by Artem S. Silchenko, Mikhail I. Kusaykin, Valeriya V. Kurilenko, Alexander M. Zakharenko, Vladimir V. Isakov, Tatyana S. Zaporozhets, Anna K. Gazha and Tatyana N. Zvyagintseva

Mar. Drugs 2013, 11(7), 2413-2430; https://doi.org/10.3390/md11072413 - 11 Jul 2013

Cited by 76 | Viewed by 11051

Abstract

Intracellular fucoidanase was isolated from the marine bacterium, Formosa algae strain KMM 3553. The first appearance of fucoidan enzymatic hydrolysis products in a cell-free extract was detected after 4 h of bacterial growth, and maximal fucoidanase activity was observed after 12 h of [...] Read more.

Intracellular fucoidanase was isolated from the marine bacterium, Formosa algae strain KMM 3553. The first appearance of fucoidan enzymatic hydrolysis products in a cell-free extract was detected after 4 h of bacterial growth, and maximal fucoidanase activity was observed after 12 h of growth. The fucoidanase displayed maximal activity in a wide range of pH values, from 6.5 to 9.1. The presence of Mg²⁺, Ca²⁺and Ba²⁺ cations strongly activated the enzyme; however, Cu²⁺ and Zn²⁺ cations had inhibitory effects on the enzymatic activity. The enzymatic activity of fucoidanase was considerably reduced after prolonged (about 60 min) incubation of the enzyme solution at 45 °C. The fucoidanase catalyzed the hydrolysis of fucoidans from Fucus evanescens and Fucus vesiculosus, but not from Saccharina cichorioides. The fucoidanase also did not hydrolyze carrageenan. Desulfated fucoidan from F. evanescens was hydrolysed very weakly in contrast to deacetylated fucoidan, which was hydrolysed more actively compared to the native fucoidan from F. evanescens. Analysis of the structure of the enzymatic products showed that the marine bacteria, F. algae, synthesized an α-l-fucanase with an endo-type action that is specific for 1→4-bonds in a polysaccharide molecule built up of alternating three- and four-linked α-l-fucopyranose residues sulfated mainly at position 2. Full article

(This article belongs to the Special Issue Selected Papers from the 1st Symposium on Marine Enzymes and Polysaccharides)

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Open AccessArticle

Domoic Acid Improves the Competitive Ability of Pseudo-nitzschia delicatissima against the Diatom Skeletonema marinoi

by Emily K. Prince, Friederike Irmer and Georg Pohnert

Mar. Drugs 2013, 11(7), 2398-2412; https://doi.org/10.3390/md11072398 - 11 Jul 2013

Cited by 29 | Viewed by 8886

Abstract

Because domoic acid, a neurotoxic secondary metabolite produced by marine diatoms in the genus Pseudo-nitzschia, is hypothesized to be part of a high affinity iron uptake system, we investigated whether domoic acid could improve the competitive ability of Pseudo-nitzschia delicatissima, and [...] Read more.

Because domoic acid, a neurotoxic secondary metabolite produced by marine diatoms in the genus Pseudo-nitzschia, is hypothesized to be part of a high affinity iron uptake system, we investigated whether domoic acid could improve the competitive ability of Pseudo-nitzschia delicatissima, and whether the availability of iron changed the outcome of competition experiments. We found that domoic acid had a slight negative effect on growth of the diatom Skeletonema marinoi when it was grown in monocultures. However, when S. marinoi was cultured with P. delicatissima the presence of domoic acid resulted in a reduction of S. marinoi cells by up to 38% and an increase in P. delicatissima cell numbers by up to 17% under iron replete conditions. Similar effects were not observed in low iron treatments. Domoic acid was not taken up by P. delicatissima cells. Overall, our results indicate that domoic acid can improve the competitive ability of Pseudo-nitzschia spp. and that iron is likely to be involved. This study provides an unusual example of indirect inhibition of competitor growth mediated by a secondary metabolite. Full article

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

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Open AccessArticle

Total Synthesis of Fellutamide B and Deoxy-Fellutamides B, C, and D

by Andrew M. Giltrap, Katie M. Cergol, Angel Pang, Warwick J. Britton and Richard J. Payne

Mar. Drugs 2013, 11(7), 2382-2397; https://doi.org/10.3390/md11072382 - 8 Jul 2013

Cited by 14 | Viewed by 8770

Abstract

The total syntheses of the marine-derived lipopeptide natural product fellutamide B and deoxy-fellutamides B, C, and D are reported. These compounds were accessed through a novel solid-phase synthetic strategy using Weinreb amide-derived resin. As part of the synthesis, a new enantioselective route to [...] Read more.

The total syntheses of the marine-derived lipopeptide natural product fellutamide B and deoxy-fellutamides B, C, and D are reported. These compounds were accessed through a novel solid-phase synthetic strategy using Weinreb amide-derived resin. As part of the synthesis, a new enantioselective route to (3R)-hydroxy lauric acid was developed utilizing a Brown allylation reaction followed by an oxidative cleavage-oxidation sequence as the key steps. The activity of these natural products, and natural product analogues was also assessed against Mycobacterium tuberculosis in vitro. Full article

(This article belongs to the Special Issue Marine Peptides and Their Mimetics)

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Open AccessArticle

Assessment of Chemical and Physico-Chemical Properties of Cyanobacterial Lipids for Biodiesel Production

by Patrícia C. M. Da Rós, Caroline S. P. Silva, Maria E. Silva-Stenico, Marli F. Fiore and Heizir F. De Castro

Mar. Drugs 2013, 11(7), 2365-2381; https://doi.org/10.3390/md11072365 - 4 Jul 2013

Cited by 58 | Viewed by 8431

Abstract

Five non-toxin producing cyanobacterial isolates from the genera Synechococcus, Trichormus, Microcystis, Leptolyngbya and Chlorogloea were examined in terms of quantity and quality as lipid feedstock for biofuel production. Under the conditions used in this study, the biomass productivity ranged from [...] Read more.

Five non-toxin producing cyanobacterial isolates from the genera Synechococcus, Trichormus, Microcystis, Leptolyngbya and Chlorogloea were examined in terms of quantity and quality as lipid feedstock for biofuel production. Under the conditions used in this study, the biomass productivity ranged from 3.7 to 52.7 mg·L⁻¹·day⁻¹ in relation to dry biomass, while the lipid productivity varied between 0.8 and 14.2 mg·L⁻¹·day⁻¹. All cyanobacterial strains evaluated yielded lipids with similar fatty acid composition to those present in the seed oils successfully used for biodiesel synthesis. However, by combining biomass and lipid productivity parameters, the greatest potential was found for Synechococcus sp. PCC7942, M. aeruginosa NPCD-1 and Trichormus sp. CENA77. The chosen lipid samples were further characterized using Fourier Transform Infrared spectroscopy (FTIR), viscosity and thermogravimetry and used as lipid feedstock for biodiesel synthesis by heterogeneous catalysis. Full article

(This article belongs to the Special Issue Compounds from Cyanobacteria)

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Induction of Apoptosis by Fucoidan in Human Leukemia U937 Cells through Activation of p38 MAPK and Modulation of Bcl-2 Family

by Hyun Soo Park, Hye Jin Hwang, Gi-Young Kim, Hee-Jae Cha, Wun-Jae Kim, Nam Deuk Kim, Young Hyun Yoo and Yung Hyun Choi

Mar. Drugs 2013, 11(7), 2347-2364; https://doi.org/10.3390/md11072347 - 4 Jul 2013

Cited by 70 | Viewed by 10413

Abstract

The present study investigated possible mechanisms on the apoptosis induction of human leukemic cells by fucoidan, a sulfated polysaccharide found in marine algae. Fucoidan treatment of cells resulted in inhibition of growth and induction of apoptosis, as measured by 3-(4,5-dimetylthiazol-2-yl)-2,5-diphenyl-tetrazolium (MTT) assay, fluorescence [...] Read more.

The present study investigated possible mechanisms on the apoptosis induction of human leukemic cells by fucoidan, a sulfated polysaccharide found in marine algae. Fucoidan treatment of cells resulted in inhibition of growth and induction of apoptosis, as measured by 3-(4,5-dimetylthiazol-2-yl)-2,5-diphenyl-tetrazolium (MTT) assay, fluorescence microscopy, DNA fragmentation, and flow cytometry analysis. The increase in apoptosis was associated with the proteolytic activation of caspases, Bid cleavage, insertion of pro-apoptotic Bax into the mitochondria, release of cytochrome c from mitochondria to cytosol, and loss of mitochondria membrane potential (MMP) in U937 cells. However, apoptosis induced by fucoidan was attenuated by caspase inhibitors, indicating that fucoidan-induced apoptosis was dependent on the activation of caspases. Furthermore, fucoidan treatment effectively activated the p38 mitogen-activated protein kinase (MAPK) and p38 MAPK inhibitor, SB203580, and significantly reduced fucoidan-induced apoptosis through inhibition of Bax translocation and caspases activation, suggesting that the activation of p38 MAPK may play a key role in fucoidan-induced apoptosis. In addition, the authors found fucoidan-induced significantly attenuated in Bcl-2 overexpressing U937 cells, and pretreatment with fucoidan and HA 14-1, a small-molecule Bcl-2 inhibitor, markedly increased fucoidan-mediated apoptosis in Bcl-2 overexpressing U937 cells. Our findings imply that we may attribute some of the biological functions of p38 MAPK and Bcl-2 to their ability to inhibit fucoidan-induced apoptosis. Full article

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Open AccessArticle

pH-Dependent Solution Structure and Activity of a Reduced Form of the Host-Defense Peptide Myticin C (Myt C) from the Mussel Mytilus galloprovincialis

by Alicia Martinez-Lopez, Jose Antonio Encinar, Regla Maria Medina-Gali, Pablo Balseiro, Pablo Garcia-Valtanen, Antonio Figueras, Beatriz Novoa and Amparo Estepa

Mar. Drugs 2013, 11(7), 2328-2346; https://doi.org/10.3390/md11072328 - 4 Jul 2013

Cited by 15 | Viewed by 7684

Abstract

Myticin C (Myt C) is a highly variable host-defense peptide (HDP) associated to the immune response in the mediterranean mussel (Mytilus galloprovincialis), which has shown to be active across species due to its strong antiviral activity against a fish rhabdovirus found [...] Read more.

Myticin C (Myt C) is a highly variable host-defense peptide (HDP) associated to the immune response in the mediterranean mussel (Mytilus galloprovincialis), which has shown to be active across species due to its strong antiviral activity against a fish rhabdovirus found in fish cells overexpressing this HDP. However, the potential antimicrobial properties of any synthetic analogue of Myt C has not yet been analysed. Thus, in this work we have synthesised the sequence of the mature peptide of Myt C variant c and analysed the structure activity relationships of its reduced (non-oxidized) form (red-MytCc). In contrast to results previously reported for oxidized isoforms of mussel myticins, red-MytCc was not active against bacteria at physiological pH and showed a moderate antiviral activity against the viral haemorrhagic septicaemia (VHS) rhabdovirus. However, its chemotactic properties remained active. Structure/function studies in neutral and acid environments by means of infrared spectroscopy indicated that the structure of red-MytCc is pH dependent, with acid media increasing its alpha-helical content. Furthermore, red-MytCc was able to efficiently aggregate artificial phospholipid membranes at low pH, as well as to inhibit the Escherichia coli growth, suggesting that this activity is attributable to its more structured form in an acidic environment. All together, these results highlight the dynamic and environmentally sensitive behavior of red-Myt C in solution, and provide important insights into Myt C structure/activity relationships and the requirements to exert its antimicrobial/immunomodulatory activities. On the other hand, the pH-dependent direct antimicrobial activity of Myt C suggests that this HDP may be a suitable template for the development of antimicrobial agents that would function selectively in specific pH environments, which are sorely needed in this “antibiotic-resistance era”. Full article

(This article belongs to the Special Issue Marine Peptides and Their Mimetics)

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Oxygenated Polyketides from Plakinastrella mamillaris as a New Chemotype of PXR Agonists

by Carmen Festa, Claudio D'Amore, Barbara Renga, Gianluigi Lauro, Simona De Marino, Maria Valeria D'Auria, Giuseppe Bifulco, Angela Zampella and Stefano Fiorucci

Mar. Drugs 2013, 11(7), 2314-2327; https://doi.org/10.3390/md11072314 - 2 Jul 2013

Cited by 38 | Viewed by 7453

Abstract

Further purification of the apolar extracts of the sponge Plakinastrella mamillaris, afforded a new oxygenated polyketide named gracilioether K, together with the previously isolated gracilioethers E–G and gracilioethers I and J. The structure of the new compound has been elucidated by extensive [...] Read more.

Further purification of the apolar extracts of the sponge Plakinastrella mamillaris, afforded a new oxygenated polyketide named gracilioether K, together with the previously isolated gracilioethers E–G and gracilioethers I and J. The structure of the new compound has been elucidated by extensive NMR (¹H and ¹³C, COSY, HSQC, HMBC, and ROESY) and ESI-MS analysis. With the exception of gracilioether F, all compounds are endowed with potent pregnane-X-receptor (PXR) agonistic activity and therefore represent a new chemotype of potential anti-inflammatory leads. Docking calculations suggested theoretical binding modes of the identified compounds, compatible with an agonistic activity on hPXR, and clarified the molecular basis of their biological activities. Full article

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

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Open AccessReview

Strategies for the Development of Conotoxins as New Therapeutic Leads

by Ryan M. Brady, Jonathan B. Baell and Raymond S. Norton

Mar. Drugs 2013, 11(7), 2293-2313; https://doi.org/10.3390/md11072293 - 28 Jun 2013

Cited by 26 | Viewed by 8338

Abstract

Peptide toxins typically bind to their target ion channels or receptors with high potency and selectivity, making them attractive leads for therapeutic development. In some cases the native peptide as it is found in the venom from which it originates can be used [...] Read more.

Peptide toxins typically bind to their target ion channels or receptors with high potency and selectivity, making them attractive leads for therapeutic development. In some cases the native peptide as it is found in the venom from which it originates can be used directly, but in many instances it is desirable to truncate and/or stabilize the peptide to improve its therapeutic properties. A complementary strategy is to display the key residues that make up the pharmacophore of the peptide toxin on a non-peptidic scaffold, thereby creating a peptidomimetic. This review exemplifies these approaches with peptide toxins from marine organisms, with a particular focus on conotoxins. Full article

(This article belongs to the Special Issue Marine Peptides and Their Mimetics)

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Nepheliosyne B, a New Polyacetylenic Acid from the New Caledonian Marine Sponge Niphates sp.

by Nathalie Legrave, Souhir Hamrouni-Buonomo, Maeva Dufies, Vincent Guérineau, Jean Vacelet, Patrick Auberger, Philippe Amade and Mohamed Mehiri

Mar. Drugs 2013, 11(7), 2282-2292; https://doi.org/10.3390/md11072282 - 27 Jun 2013

Cited by 9 | Viewed by 6848

Abstract

A new C₄₇ polyoxygenated acetylenic acid, nepheliosyne B (2), along with the previously described nepheliosyne A (1), have been isolated from the New Caledonian marine sponge Niphates sp. Their structures have been elucidated on the basis of extensive [...] Read more.

A new C₄₇ polyoxygenated acetylenic acid, nepheliosyne B (2), along with the previously described nepheliosyne A (1), have been isolated from the New Caledonian marine sponge Niphates sp. Their structures have been elucidated on the basis of extensive spectroscopic analyses. These metabolites exhibited a moderate cytotoxicity against K562, U266, SKM1, and Kasumi cancer cell lines. Full article

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Open AccessReview

Alternative Sources of n-3 Long-Chain Polyunsaturated Fatty Acids in Marine Microalgae

by Dulce Alves Martins, Luísa Custódio, Luísa Barreira, Hugo Pereira, Radhouan Ben-Hamadou, João Varela and Khalid M. Abu-Salah

Mar. Drugs 2013, 11(7), 2259-2281; https://doi.org/10.3390/md11072259 - 27 Jun 2013

Cited by 243 | Viewed by 20803

Abstract

The main source of n-3 long-chain polyunsaturated fatty acids (LC-PUFA) in human nutrition is currently seafood, especially oily fish. Nonetheless, due to cultural or individual preferences, convenience, geographic location, or awareness of risks associated to fatty fish consumption, the intake of fatty [...] Read more.

The main source of n-3 long-chain polyunsaturated fatty acids (LC-PUFA) in human nutrition is currently seafood, especially oily fish. Nonetheless, due to cultural or individual preferences, convenience, geographic location, or awareness of risks associated to fatty fish consumption, the intake of fatty fish is far from supplying the recommended dietary levels. The end result observed in most western countries is not only a low supply of n-3 LC-PUFA, but also an unbalance towards the intake of n-6 fatty acids, resulting mostly from the consumption of vegetable oils. Awareness of the benefits of LC-PUFA in human health has led to the use of fish oils as food supplements. However, there is a need to explore alternatives sources of LC-PUFA, especially those of microbial origin. Microalgae species with potential to accumulate lipids in high amounts and to present elevated levels of n-3 LC-PUFA are known in marine phytoplankton. This review focuses on sources of n-3 LC-PUFA, namely eicosapentaenoic and docosahexaenoic acids, in marine microalgae, as alternatives to fish oils. Based on current literature, examples of marketed products and potentially new species for commercial exploitation are presented. Full article

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

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Interpreting the Possible Ecological Role(s) of Cyanotoxins: Compounds for Competitive Advantage and/or Physiological Aide?

by Aleicia Holland and Susan Kinnear

Mar. Drugs 2013, 11(7), 2239-2258; https://doi.org/10.3390/md11072239 - 27 Jun 2013

Cited by 124 | Viewed by 10305

Abstract

To date, most research on freshwater cyanotoxin(s) has focused on understanding the dynamics of toxin production and decomposition, as well as evaluating the environmental conditions that trigger toxin production, all with the objective of informing management strategies and options for risk reduction. Comparatively [...] Read more.

To date, most research on freshwater cyanotoxin(s) has focused on understanding the dynamics of toxin production and decomposition, as well as evaluating the environmental conditions that trigger toxin production, all with the objective of informing management strategies and options for risk reduction. Comparatively few research studies have considered how this information can be used to understand the broader ecological role of cyanotoxin(s), and the possible applications of this knowledge to the management of toxic blooms. This paper explores the ecological, toxicological, and genetic evidence for cyanotoxin production in natural environments. The possible evolutionary advantages of toxin production are grouped into two main themes: That of “competitive advantage” or “physiological aide”. The first grouping illustrates how compounds produced by cyanobacteria may have originated from the need for a cellular defence mechanism, in response to grazing pressure and/or resource competition. The second grouping considers the contribution that secondary metabolites make to improved cellular physiology, through benefits to homeostasis, photosynthetic efficiencies, and accelerated growth rates. The discussion also includes other factors in the debate about possible evolutionary roles for toxins, such as different modes of exposures and effects on non-target (i.e., non-competitive) species. The paper demonstrates that complex and multiple factors are at play in driving evolutionary processes in aquatic environments. This information may provide a fresh perspective on managing toxic blooms, including the need to use a “systems approach” to understand how physico-chemical conditions, as well biological stressors, interact to trigger toxin production. Full article

(This article belongs to the Special Issue Compounds from Cyanobacteria)

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Mar. Drugs, Volume 11, Issue 7 (July 2013) – 26 articles , Pages 2239-2694

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