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Mar. Drugs, Volume 11, Issue 11 (November 2013), Pages 4127-4697

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Open AccessArticle Molecular Docking Studies of Marine Diterpenes as Inhibitors of Wild-Type and Mutants HIV-1 Reverse Transcriptase
Mar. Drugs 2013, 11(11), 4127-4143; doi:10.3390/md11114127
Received: 30 July 2013 / Revised: 11 September 2013 / Accepted: 2 October 2013 / Published: 29 October 2013
Cited by 5 | PDF Full-text (1386 KB) | HTML Full-text | XML Full-text
Abstract
AIDS is a pandemic responsible for more than 35 million deaths. The emergence of resistant mutations due to drug use is the biggest cause of treatment failure. Marine organisms are sources of different molecules, some of which offer promising HIV-1 reverse transcriptase (RT)
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AIDS is a pandemic responsible for more than 35 million deaths. The emergence of resistant mutations due to drug use is the biggest cause of treatment failure. Marine organisms are sources of different molecules, some of which offer promising HIV-1 reverse transcriptase (RT) inhibitory activity, such as the diterpenes dolabelladienotriol (THD, IC50 = 16.5 µM), (6R)-6-hydroxydichotoma-3,14-diene-1,17-dial (HDD, IC50 = 10 µM) and (6R)-6-acetoxydichotoma-3,14-diene-1,17-dial (ADD, IC50 = 35 µM), isolated from a brown algae of the genus Dictyota, showing low toxicity. In this work, we evaluated the structure-activity relationship (SAR) of THD, HDD and ADD as anti HIV-1 RT, using a molecular modeling approach. The analyses of stereoelectronic parameters revealed a direct relationship between activity and HOMO (Highest Occupied Molecular Orbital)-LUMO (Lowest Unoccupied Molecular Orbital) gap (ELUMO–EHOMO), where antiviral profile increases with larger HOMO-LUMO gap values. We also performed molecular docking studies of THD into HIV-1 RT wild-type and 12 different mutants, which showed a seahorse conformation, hydrophobic interactions and hydrogen bonds with important residues of the binding pocket. Based on in vitro experiments and docking studies, we demonstrated that mutations have little influence in positioning and interactions of THD. Following a rational drug design, we suggest a modification of THD to improve its biological activity. Full article
Open AccessArticle Formation of a Volunteer Harmful Algal Bloom Network in British Columbia, Canada, Following an Outbreak of Diarrhetic Shellfish Poisoning
Mar. Drugs 2013, 11(11), 4144-4157; doi:10.3390/md11114144
Received: 30 July 2013 / Revised: 3 October 2013 / Accepted: 15 October 2013 / Published: 29 October 2013
Cited by 2 | PDF Full-text (529 KB) | HTML Full-text | XML Full-text
Abstract
Evidence for shellfish toxin illness in British Columbia (BC) on the west coast of Canada can be traced back to 1793. For over two hundred years, domestically acquired bivalve shellfish toxin illnesses in BC were solely ascribed to paralytic shellfish poisonings caused by
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Evidence for shellfish toxin illness in British Columbia (BC) on the west coast of Canada can be traced back to 1793. For over two hundred years, domestically acquired bivalve shellfish toxin illnesses in BC were solely ascribed to paralytic shellfish poisonings caused by algal blooms of Alexandrium. This changed in 2011, when BC experienced its first outbreak of diarrhetic shellfish poisoning (DSP). As a result of this outbreak, Canada’s first DSP symposium was held in November, 2012, in North Vancouver, BC. Three of the objectives of the symposium were to provide a forum to educate key stakeholders on this emerging issue, to identify research and surveillance priorities and to create a DSP network. The purpose of this paper is to review what is known about shellfish poisoning in BC and to describe a novel volunteer network that arose following the symposium. The newly formed network was designed for industry shellfish growers to identify harmful algae bloom events, so that they may take actions to mitigate the effects of harmful blooms on shellfish morbidity. The network will also inform public health and regulatory stakeholders of potentially emerging issues in shellfish growing areas. Full article
Open AccessArticle A Stable-Isotope Mass Spectrometry-Based Metabolic Footprinting Approach to Analyze Exudates from Phytoplankton
Mar. Drugs 2013, 11(11), 4158-4175; doi:10.3390/md11114158
Received: 12 August 2013 / Revised: 13 September 2013 / Accepted: 1 October 2013 / Published: 29 October 2013
Cited by 5 | PDF Full-text (890 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Phytoplankton exudates play an important role in pelagic ecology and biogeochemical cycles of elements. Exuded compounds fuel the microbial food web and often encompass bioactive secondary metabolites like sex pheromones, allelochemicals, antibiotics, or feeding attractants that mediate biological interactions. Despite this importance, little
[...] Read more.
Phytoplankton exudates play an important role in pelagic ecology and biogeochemical cycles of elements. Exuded compounds fuel the microbial food web and often encompass bioactive secondary metabolites like sex pheromones, allelochemicals, antibiotics, or feeding attractants that mediate biological interactions. Despite this importance, little is known about the bioactive compounds present in phytoplankton exudates. We report a stable-isotope metabolic footprinting method to characterise exudates from aquatic autotrophs. Exudates from 13C-enriched alga were concentrated by solid phase extraction and analysed by high-resolution Fourier transform ion cyclotron resonance mass spectrometry. We used the harmful algal bloom forming dinoflagellate Alexandrium tamarense to prove the method. An algorithm was developed to automatically pinpoint just those metabolites with highly 13C-enriched isotope signatures, allowing us to discover algal exudates from the complex seawater background. The stable-isotope pattern (SIP) of the detected metabolites then allowed for more accurate assignment to an empirical formula, a critical first step in their identification. This automated workflow provides an effective way to explore the chemical nature of the solutes exuded from phytoplankton cells and will facilitate the discovery of novel dissolved bioactive compounds. Full article
(This article belongs to the collection Bioactive Compounds from Marine Plankton)
Open AccessArticle Anti HSV-1 Activity of Halistanol Sulfate and Halistanol Sulfate C Isolated from Brazilian Marine Sponge Petromica citrina (Demospongiae)
Mar. Drugs 2013, 11(11), 4176-4192; doi:10.3390/md11114176
Received: 2 September 2013 / Revised: 18 September 2013 / Accepted: 30 September 2013 / Published: 29 October 2013
Cited by 3 | PDF Full-text (812 KB) | HTML Full-text | XML Full-text
Abstract
The n-butanol fraction (BF) obtained from the crude extract of the marine sponge Petromica citrina, the halistanol-enriched fraction (TSH fraction), and the isolated compounds halistanol sulfate (1) and halistanol sulfate C (2), were evaluated for their inhibitory
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The n-butanol fraction (BF) obtained from the crude extract of the marine sponge Petromica citrina, the halistanol-enriched fraction (TSH fraction), and the isolated compounds halistanol sulfate (1) and halistanol sulfate C (2), were evaluated for their inhibitory effects on the replication of the Herpes Simplex Virus type 1 (HSV-1, KOS strain) by the viral plaque number reduction assay. The TSH fraction was the most effective against HSV-1 replication (SI = 15.33), whereas compounds 1 (SI = 2.46) and 2 (SI = 1.95) were less active. The most active fraction and these compounds were also assayed to determine the viral multiplication step(s) upon which they act as well as their potential synergistic effects. The anti-HSV-1 activity detected was mediated by the inhibition of virus attachment and by the penetration into Vero cells, the virucidal effect on virus particles, and by the impairment in levels of ICP27 and gD proteins of HSV-1. In summary, these results suggest that the anti-HSV-1 activity of TSH fraction detected is possibly related to the synergic effects of compounds 1 and 2. Full article
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Open AccessArticle Anti-Diabetic Effect of Balanced Deep-Sea Water and Its Mode of Action in High-Fat Diet Induced Diabetic Mice
Mar. Drugs 2013, 11(11), 4193-4212; doi:10.3390/md11114193
Received: 2 August 2013 / Revised: 11 September 2013 / Accepted: 8 October 2013 / Published: 29 October 2013
Cited by 12 | PDF Full-text (710 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In this study, we investigated the effects of balanced deep-sea water (BDSW) on hyperglycemia and glucose intolerance in high-fat diet (HFD)-induced diabetic C57BL/6J mice. BDSW was prepared by mixing deep-sea water (DSW) mineral extracts and desalinated water to give a final hardness of
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In this study, we investigated the effects of balanced deep-sea water (BDSW) on hyperglycemia and glucose intolerance in high-fat diet (HFD)-induced diabetic C57BL/6J mice. BDSW was prepared by mixing deep-sea water (DSW) mineral extracts and desalinated water to give a final hardness of 500–2000. Mice given an HFD with BDSW showed lowered fasting plasma glucose levels compared to HFD-fed mice. Oral and intraperitoneal glucose tolerance tests showed that BDSW improves impaired glucose tolerance in HFD-fed mice. Histopathological evaluation of the pancreas showed that BDSW recovers the size of the pancreatic islets of Langerhans, and increases the secretion of insulin and glucagon in HFD-fed mice. Quantitative reverse transcription polymerase chain reaction results revealed that the expression of hepatic genes involved in glucogenesis, glycogenolysis and glucose oxidation were suppressed, while those in glucose uptake, β-oxidation, and glucose oxidation in muscle were increased in mice fed HFD with BDSW. BDSW increased AMP-dependent kinase (AMPK) phosphorylation in 3T3-L1 pre- and mature adipocytes and improved impaired AMPK phosphorylation in the muscles and livers of HFD-induced diabetic mice. BDSW stimulated phosphoinositol-3-kinase and AMPK pathway-mediated glucose uptake in 3T3-L1 adipocytes. Taken together, these results suggest that BDSW has potential as an anti-diabetic agent, given its ability to suppress hyperglycemia and improve glucose intolerance by increasing glucose uptake. Full article
Open AccessArticle Evidence of Accelerated Evolution and Ectodermal-Specific Expression of Presumptive BDS Toxin cDNAs from Anemonia viridis
Mar. Drugs 2013, 11(11), 4213-4231; doi:10.3390/md11114213
Received: 21 August 2013 / Revised: 10 September 2013 / Accepted: 13 September 2013 / Published: 30 October 2013
Cited by 6 | PDF Full-text (2471 KB) | HTML Full-text | XML Full-text
Abstract
Anemonia viridis is a widespread and extensively studied Mediterranean species of sea anemone from which a large number of polypeptide toxins, such as blood depressing substances (BDS) peptides, have been isolated. The first members of this class, BDS-1 and BDS-2, are polypeptides belonging
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Anemonia viridis is a widespread and extensively studied Mediterranean species of sea anemone from which a large number of polypeptide toxins, such as blood depressing substances (BDS) peptides, have been isolated. The first members of this class, BDS-1 and BDS-2, are polypeptides belonging to the β-defensin fold family and were initially described for their antihypertensive and antiviral activities. BDS-1 and BDS-2 are 43 amino acid peptides characterised by three disulfide bonds that act as neurotoxins affecting Kv3.1, Kv3.2 and Kv3.4 channel gating kinetics. In addition, BDS-1 inactivates the Nav1.7 and Nav1.3 channels. The development of a large dataset of A. viridis expressed sequence tags (ESTs) and the identification of 13 putative BDS-like cDNA sequences has attracted interest, especially as scientific and diagnostic tools. A comparison of BDS cDNA sequences showed that the untranslated regions are more conserved than the protein-coding regions. Moreover, the KA/KS ratios calculated for all pairwise comparisons showed values greater than 1, suggesting mechanisms of accelerated evolution. The structures of the BDS homologs were predicted by molecular modelling. All toxins possess similar 3D structures that consist of a triple-stranded antiparallel β-sheet and an additional small antiparallel β-sheet located downstream of the cleavage/maturation site; however, the orientation of the triple-stranded β-sheet appears to differ among the toxins. To characterise the spatial expression profile of the putative BDS cDNA sequences, tissue-specific cDNA libraries, enriched for BDS transcripts, were constructed. In addition, the proper amplification of ectodermal or endodermal markers ensured the tissue specificity of each library. Sequencing randomly selected clones from each library revealed ectodermal-specific expression of ten BDS transcripts, while transcripts of BDS-8, BDS-13, BDS-14 and BDS-15 failed to be retrieved, likely due to under-representation in our cDNA libraries. The calculation of the relative abundance of BDS transcripts in the cDNA libraries revealed that BDS-1, BDS-3, BDS-4, BDS-5 and BDS-6 are the most represented transcripts. Full article
Open AccessArticle Chemical Diversity as a Function of Temperature in Six Northern Diatom Species
Mar. Drugs 2013, 11(11), 4232-4245; doi:10.3390/md11114232
Received: 12 August 2013 / Revised: 17 October 2013 / Accepted: 17 October 2013 / Published: 30 October 2013
Cited by 4 | PDF Full-text (578 KB) | HTML Full-text | XML Full-text
Abstract
In this study, we investigate how metabolic fingerprints are related to temperature. Six common northern temperate diatoms (Attheya longicornis, Chaetoceros socialis, Chaetoceros furcellatus, Porosira glacialis, Skeletonema marinoi, and Thalassiosira gravida) were cultivated at two different temperatures,
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In this study, we investigate how metabolic fingerprints are related to temperature. Six common northern temperate diatoms (Attheya longicornis, Chaetoceros socialis, Chaetoceros furcellatus, Porosira glacialis, Skeletonema marinoi, and Thalassiosira gravida) were cultivated at two different temperatures, 0.5 and 8.5 °C. To exclude metabolic variations due to differences in growth rates, the growth rates were kept similar by performing the experiments under light limited conditions but in exponential growth phase. Growth rates and maximum quantum yield of photosynthesis were measured and interpreted as physiological variables, and metabolic fingerprints were acquired by high-resolution mass spectrometry. The chemical diversity varied substantially between the two temperatures for the tested species, ranging from 31% similarity for C. furcellatus and P. glacialis to 81% similarity for A. longicornis. The chemical diversity was generally highest at the lowest temperature. Full article
(This article belongs to the Special Issue Metabolites in Diatoms)
Open AccessArticle LC-PUFA-Enriched Oil Production by Microalgae: Accumulation of Lipid and Triacylglycerols Containing n-3 LC-PUFA Is Triggered by Nitrogen Limitation and Inorganic Carbon Availability in the Marine Haptophyte Pavlova lutheri
Mar. Drugs 2013, 11(11), 4246-4266; doi:10.3390/md11114246
Received: 13 September 2013 / Revised: 8 October 2013 / Accepted: 14 October 2013 / Published: 30 October 2013
Cited by 18 | PDF Full-text (670 KB) | HTML Full-text | XML Full-text
Abstract
In most microalgal species, triacyglycerols (TAG) contain mostly saturated and monounsaturated fatty acids, rather than PUFA, while PUFA-enriched oil is the form most desirable for dietary intake. The ability of some species to produce LC-PUFA-enriched oil is currently of specific interest. In this
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In most microalgal species, triacyglycerols (TAG) contain mostly saturated and monounsaturated fatty acids, rather than PUFA, while PUFA-enriched oil is the form most desirable for dietary intake. The ability of some species to produce LC-PUFA-enriched oil is currently of specific interest. In this work, we investigated the role of sodium bicarbonate availability on lipid accumulation and n-3 LC-PUFA partitioning into TAG during batch cultivation of Pavlova lutheri. Maximum growth and nitrate uptake exhibit an optimum concentration and threshold tolerance to bicarbonate addition (~9 mM) above which both parameters decreased. Nonetheless, the transient highest cellular lipid and TAG contents were obtained at 18 mM bicarbonate, immediately after combined alkaline pH stress and nitrate depletion (day nine), while oil body and TAG accumulation were highly repressed with low carbon supply (2 mM). Despite decreases in the proportions of EPA and DHA, maximum volumetric and cellular EPA and DHA contents were obtained at this stage due to accumulation of TAG containing EPA/DHA. TAG accounted for 74% of the total fatty acid per cell, containing 55% and 67% of the overall cellular EPA and DHA contents, respectively. These results clearly demonstrate that inorganic carbon availability and elevated pH represent two limiting factors for lipid and TAG accumulation, as well as n-3 LC-PUFA partitioning into TAG, under nutrient-depleted P. lutheri cultures. Full article
(This article belongs to the Special Issue Marine Fatty Acids-2013)
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Open AccessArticle Cytotoxic Effects of Fucoidan Nanoparticles against Osteosarcoma
Mar. Drugs 2013, 11(11), 4267-4278; doi:10.3390/md11114267
Received: 6 September 2013 / Revised: 18 October 2013 / Accepted: 18 October 2013 / Published: 30 October 2013
Cited by 11 | PDF Full-text (1177 KB) | HTML Full-text | XML Full-text
Abstract
In this study, we analyzed the size-dependent bioactivities of fucoidan by comparing the cytotoxic effects of native fucoidan and fucoidan lipid nanoparticles on osteosarcoma in vitro and in vivo. In vitro experiments indicated that nanoparticle fucoidan induced apoptosis of an osteosarcoma cell
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In this study, we analyzed the size-dependent bioactivities of fucoidan by comparing the cytotoxic effects of native fucoidan and fucoidan lipid nanoparticles on osteosarcoma in vitro and in vivo. In vitro experiments indicated that nanoparticle fucoidan induced apoptosis of an osteosarcoma cell line more efficiently than native fucoidan. The more potent effects of nanoparticle fucoidan, relative to native fucoidan, were confirmed in vivo using a xenograft osteosarcoma model. Caco-2 cell transport studies showed that permeation of nanoparticle fucoidan was higher than native fucoidan. The higher bioactivity and superior bioavailability of nanoparticle fucoidan could potentially be utilized to develop novel therapies for osteosarcoma. Full article
(This article belongs to the collection Marine Compounds and Cancer)
Open AccessArticle Efficient Screening of Marine Extracts for Protease Inhibitors by Combining FRET Based Activity Assays and Surface Plasmon Resonance Spectroscopy Based Binding Assays
Mar. Drugs 2013, 11(11), 4279-4293; doi:10.3390/md11114279
Received: 3 July 2013 / Revised: 20 October 2013 / Accepted: 21 October 2013 / Published: 30 October 2013
Cited by 2 | PDF Full-text (987 KB) | HTML Full-text | XML Full-text
Abstract
The screening of extracts from marine organisms is a widely used strategy to discover new drug leads. A common problem in the screening process is the generation of false positive hits through unspecific effects from the complex chemical composition of the crude extracts.
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The screening of extracts from marine organisms is a widely used strategy to discover new drug leads. A common problem in the screening process is the generation of false positive hits through unspecific effects from the complex chemical composition of the crude extracts. In this study, we explored a combination of a fluorescence resonance energy transfer (FRET) based activity assay and a surface plasmon resonance (SPR) based binding assay to avoid this problem. An aqueous extract was prepared from rest raw material of the Norwegian spring spawning herring, and further fractionated by methanol solubility and solid phase extraction. FRET based activity assays were used to determine the influence of each extract on the activity of different proteases. Several extracts showed more than 50% inhibition. The inhibition mechanisms were elucidated by SPR based competition experiments with known inhibitors. For the secreted aspartic proteases 1, 2, 3 and HIV-1 protease, the results indicated that some extracts contain inhibitors interacting specifically with the active site of the enzymes. The study shows that a combination of an activity assay and an SPR based binding assay is a powerful tool to identify potent inhibitors in marine extracts. Furthermore, the study shows that marine vertebrates offer an interesting source for new bioactive compounds, although they have rarely been explored for this purpose. Full article
Open AccessArticle Anxiolytic-Like Effect of a Salmon Phospholipopeptidic Complex Composed of Polyunsaturated Fatty Acids and Bioactive Peptides
Mar. Drugs 2013, 11(11), 4294-4317; doi:10.3390/md11114294
Received: 17 July 2013 / Revised: 20 August 2013 / Accepted: 22 August 2013 / Published: 30 October 2013
Cited by 2 | PDF Full-text (970 KB) | HTML Full-text | XML Full-text
Abstract
A phospholipopeptidic complex obtained by the enzymatic hydrolysis of salmon heads in green conditions; exert anxiolytic-like effects in a time and dose-dependent manner, with no affection of locomotor activity. This study focused on the physico-chemical properties of the lipidic and peptidic fractions from
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A phospholipopeptidic complex obtained by the enzymatic hydrolysis of salmon heads in green conditions; exert anxiolytic-like effects in a time and dose-dependent manner, with no affection of locomotor activity. This study focused on the physico-chemical properties of the lipidic and peptidic fractions from this natural product. The characterization of mineral composition, amino acid and fatty acids was carried out. Stability of nanoemulsions allowed us to realize a behavioral study conducted with four different tests on 80 mice. This work highlighted the dose dependent effects of the natural complex and its various fractions over a period of 14 days compared to a conventional anxiolytic. The intracellular redox status of neural cells was evaluated in order to determine the free radicals scavenging potential of these products in the central nervous system (CNS), after mice sacrifice. The complex peptidic fraction showed a strong scavenging property and similar results were found for the complex as well as its lipidic fraction. For the first time, the results of this study showed the anxiolytic-like and neuroprotective properties of a phospholipopeptidic complex extracted from salmon head. The applications on anxiety disorders might be relevant, depending on the doses, the fraction used and the chronicity of the supplementation. Full article
(This article belongs to the Special Issue Marine Fatty Acids-2013)
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Open AccessArticle New Diterpenoids from Soft Coral Sarcophyton ehrenbergi
Mar. Drugs 2013, 11(11), 4318-4327; doi:10.3390/md11114318
Received: 23 September 2013 / Revised: 18 October 2013 / Accepted: 22 October 2013 / Published: 30 October 2013
Cited by 11 | PDF Full-text (637 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Continuing chemical investigation on the acetone extracts of the soft coral Sarcophyton ehrenbergi collected off the coast of San-hsian-tai, Taitong County, Taiwan led to the isolation of two new diterpenoids, ehrenbergol C and acetyl ehrenberoxide B (1 and 2). The structures
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Continuing chemical investigation on the acetone extracts of the soft coral Sarcophyton ehrenbergi collected off the coast of San-hsian-tai, Taitong County, Taiwan led to the isolation of two new diterpenoids, ehrenbergol C and acetyl ehrenberoxide B (1 and 2). The structures of these isolated metabolites were elucidated through extensive spectroscopic analyses. Moreover, in vitro tests show that compounds 1 and 2 displayed antiviral activity towards human cytomegalovirus, with EC50 of 20 and 8.0 µg/mL, respectively. Full article
Open AccessArticle Antiproliferative Activity of Cyanophora paradoxa Pigments in Melanoma, Breast and Lung Cancer Cells
Mar. Drugs 2013, 11(11), 4390-4406; doi:10.3390/md11114390
Received: 18 July 2013 / Revised: 4 September 2013 / Accepted: 9 October 2013 / Published: 1 November 2013
Cited by 5 | PDF Full-text (585 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The glaucophyte Cyanophora paradoxa (Cp) was chemically investigated to identify pigments efficiently inhibiting malignant melanoma, mammary carcinoma and lung adenocarcinoma cells growth. Cp water and ethanol extracts significantly inhibited the growth of the three cancer cell lines in vitro, at
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The glaucophyte Cyanophora paradoxa (Cp) was chemically investigated to identify pigments efficiently inhibiting malignant melanoma, mammary carcinoma and lung adenocarcinoma cells growth. Cp water and ethanol extracts significantly inhibited the growth of the three cancer cell lines in vitro, at 100 µg·mL−1. Flash chromatography of the Cp ethanol extract, devoid of c-phycocyanin and allophycocyanin, enabled the collection of eight fractions, four of which strongly inhibited cancer cells growth at 100 µg·mL−1. Particularly, two fractions inhibited more than 90% of the melanoma cells growth, one inducing apoptosis in the three cancer cells lines. The detailed analysis of Cp pigment composition resulted in the discrimination of 17 molecules, ten of which were unequivocally identified by high resolution mass spectrometry. Pheophorbide a, β-cryptoxanthin and zeaxanthin were the three main pigments or derivatives responsible for the strong cytotoxicity of Cp fractions in cancer cells. These data point to Cyanophora paradoxa as a new microalgal source to purify potent anticancer pigments, and demonstrate for the first time the strong antiproliferative activity of zeaxanthin and β-cryptoxanthin in melanoma cells. Full article
Open AccessArticle New Constituents from the Korean Sponge Plakortis simplex
Mar. Drugs 2013, 11(11), 4407-4418; doi:10.3390/md11114407
Received: 10 July 2013 / Revised: 30 September 2013 / Accepted: 14 October 2013 / Published: 5 November 2013
Cited by 3 | PDF Full-text (502 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Six new cyclic peroxides (16) were isolated from the Korean sponge Plakortis simplex, along with two new alkylpyridinium alkaloids (7 and 8). The structures of these compounds were completely determined by a combination of NMR analysis
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Six new cyclic peroxides (16) were isolated from the Korean sponge Plakortis simplex, along with two new alkylpyridinium alkaloids (7 and 8). The structures of these compounds were completely determined by a combination of NMR analysis and chemical reactions. Compounds 16 exhibited cytotoxic/antifungal activities against RAW264.7 cells and Candida albicans. Full article
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Open AccessArticle Crambescidin-816 Acts as a Fungicidal with More Potency than Crambescidin-800 and -830, Inducing Cell Cycle Arrest, Increased Cell Size and Apoptosis in Saccharomyces cerevisiae
Mar. Drugs 2013, 11(11), 4419-4434; doi:10.3390/md11114419
Received: 29 August 2013 / Revised: 25 October 2013 / Accepted: 29 October 2013 / Published: 8 November 2013
Cited by 10 | PDF Full-text (935 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In this paper, we show the effect of crambescidin-816, -800, and -830 on Saccharomyces cerevisiae viability. We determined that, of the three molecules tested, crambescidin-816 was the most potent. Based on this result, we continued by determining the effect of crambescidin-816 on the
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In this paper, we show the effect of crambescidin-816, -800, and -830 on Saccharomyces cerevisiae viability. We determined that, of the three molecules tested, crambescidin-816 was the most potent. Based on this result, we continued by determining the effect of crambescidin-816 on the cell cycle of this yeast. The compound induced cell cycle arrest in G2/M followed by an increase in cell DNA content and size. When the type of cell death was analyzed, we observed that crambescidin-816 induced apoptosis. The antifungal effect indicates that crambescidins, and mostly crambescidin-816, could serve as a lead compound to fight fungal infections. Full article
Open AccessArticle Omega-3 Fatty Acids Modulate Weibel-Palade Body Degranulation and Actin Cytoskeleton Rearrangement in PMA-Stimulated Human Umbilical Vein Endothelial Cells
Mar. Drugs 2013, 11(11), 4435-4450; doi:10.3390/md11114435
Received: 2 September 2013 / Revised: 15 October 2013 / Accepted: 22 October 2013 / Published: 8 November 2013
Cited by 4 | PDF Full-text (738 KB) | HTML Full-text | XML Full-text
Abstract
Long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs) produce cardiovascular benefits by improving endothelial function. Endothelial cells store von Willebrand factor (vWF) in cytoplasmic Weibel-Palade bodies (WPBs). We examined whether LC n-3 PUFAs regulate WPB degranulation using cultured human umbilical
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Long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs) produce cardiovascular benefits by improving endothelial function. Endothelial cells store von Willebrand factor (vWF) in cytoplasmic Weibel-Palade bodies (WPBs). We examined whether LC n-3 PUFAs regulate WPB degranulation using cultured human umbilical vein endothelial cells (HUVECs). HUVECs were incubated with or without 75 or 120 µM docosahexaenoic acid or eicosapentaenoic acid for 5 days at 37 °C. WPB degranulation was stimulated using phorbol 12-myristate 13-acetate (PMA), and this was assessed by immunocytochemical staining for vWF. Actin reorganization was determined using phalloidin-TRITC staining. We found that PMA stimulated WPB degranulation, and that this was significantly reduced by prior incubation of cells with LC n-3 PUFAs. In these cells, WPBs had rounded rather than rod-shaped morphology and localized to the perinuclear region, suggesting interference with cytoskeletal remodeling that is necessary for complete WPB degranulation. In line with this, actin rearrangement was altered in cells containing perinuclear WPBs, where cells exhibited a thickened actin rim in the absence of prominent cytoplasmic stress fibers. These findings indicate that LC n-3 PUFAs provide some protection against WBP degranulation, and may contribute to an improved understanding of the anti-thrombotic effects previously attributed to LC n-3 PUFAs. Full article
(This article belongs to the Special Issue Marine Fatty Acids-2013)
Open AccessArticle Smenamides A and B, Chlorinated Peptide/Polyketide Hybrids Containing a Dolapyrrolidinone Unit from the Caribbean Sponge Smenospongia aurea. Evaluation of Their Role as Leads in Antitumor Drug Research
Mar. Drugs 2013, 11(11), 4451-4463; doi:10.3390/md11114451
Received: 27 September 2013 / Revised: 25 October 2013 / Accepted: 25 October 2013 / Published: 8 November 2013
Cited by 6 | PDF Full-text (553 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
An in-depth study of the secondary metabolites contained in the Caribbean sponge Smenospongia aurea led to the isolation of smenamide A (1) and B (2), hybrid peptide/polyketide compounds containing a dolapyrrolidinone unit. Their structures were elucidated using high-resolution ESI-MS/MS
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An in-depth study of the secondary metabolites contained in the Caribbean sponge Smenospongia aurea led to the isolation of smenamide A (1) and B (2), hybrid peptide/polyketide compounds containing a dolapyrrolidinone unit. Their structures were elucidated using high-resolution ESI-MS/MS and homo- and heteronuclear 2D NMR experiments. Structures of smenamides suggested that they are products of the cyanobacterial metabolism, and 16S rRNA metagenomic analysis detected Synechococcus spongiarum as the only cyanobacterium present in S. aurea. Smenamides showed potent cytotoxic activity at nanomolar levels on lung cancer Calu-1 cells, which for compound 1 is exerted through a clear pro-apoptotic mechanism. This makes smenamides promising leads for antitumor drug design. Full article
(This article belongs to the Special Issue Marine Secondary Metabolites)
Open AccessArticle Isolation and Structural Characterization of a Novel Antioxidant Mannoglucan from a Marine Bubble Snail, Bullacta exarata (Philippi)
Mar. Drugs 2013, 11(11), 4464-4477; doi:10.3390/md11114464
Received: 11 September 2013 / Revised: 12 October 2013 / Accepted: 12 October 2013 / Published: 11 November 2013
Cited by 5 | PDF Full-text (964 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Bullacta exarata is one of the most economically important aquatic species in China, noted for not only its delicious taste and nutritional value, but also for its pharmacological activities. In order to explore its potential in medical applications, a mannoglucan designated as BEPS-IB
[...] Read more.
Bullacta exarata is one of the most economically important aquatic species in China, noted for not only its delicious taste and nutritional value, but also for its pharmacological activities. In order to explore its potential in medical applications, a mannoglucan designated as BEPS-IB was isolated and purified from the foot muscle of B. exarata after papain digestion. Chemical composition analysis indicated BEPS-IB contained mainly d-glucose and d-mannose in a molar ratio of 1:0.52, with an average molecular weight of about 94 kDa. The linkage information was determined by methylation analysis, and the anomeric configuration and chain linkage were confirmed by IR and 2D NMR. The results indicated BEPS-IB was composed of Glcp6Manp heptasaccharide repeating unit in the backbone, with occasional branch chains of mannose residues (14%) occurring in the backbone mannose. Further antioxidant assay indicated BEPS-IB exhibited positive antioxidant activity in scavenging superoxide radicals and reducing power. This is the first report on the structure and bioactivity of the mannoglucan from the B. exarata. Full article
(This article belongs to the collection Marine Polysaccharides)
Open AccessArticle Chlorinated Didemnins from the Tunicate Trididemnum solidum
Mar. Drugs 2013, 11(11), 4478-4486; doi:10.3390/md11114478
Received: 23 September 2013 / Revised: 25 October 2013 / Accepted: 29 October 2013 / Published: 11 November 2013
Cited by 2 | PDF Full-text (475 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Chemical investigation of the tunicate Trididemnum solidum resulted in the isolation of two new chlorinated compounds belonging to the didemnin class, along with two known compounds didemnin A and didemnin B. The structural determination of the compounds was based on extensive NMR and
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Chemical investigation of the tunicate Trididemnum solidum resulted in the isolation of two new chlorinated compounds belonging to the didemnin class, along with two known compounds didemnin A and didemnin B. The structural determination of the compounds was based on extensive NMR and mass spectroscopic analysis. The isolated compounds 14 were tested for their anti-inflammatory activity using in vitro assays for inhibition of inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-κB) activity. The anti-cell proliferative activity of the above compounds was also evaluated against four solid tumor cell lines. Full article
Open AccessArticle Derivatives of Salarin A, Salarin C and Tulearin A—Fascaplysinopsis sp. Metabolites
Mar. Drugs 2013, 11(11), 4487-4509; doi:10.3390/md11114487
Received: 30 August 2013 / Revised: 26 September 2013 / Accepted: 9 October 2013 / Published: 11 November 2013
Cited by 2 | PDF Full-text (1016 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Derivatives of salarin A, salarin C and tulearin A, three new cytotoxic sponge derived nitrogenous macrolides, were prepared and bio-evaluated as inhibitors of K562 leukemia cells. Interesting preliminary SAR (structure activity relationship) information was obtained from the products. The most sensitive functionalities were
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Derivatives of salarin A, salarin C and tulearin A, three new cytotoxic sponge derived nitrogenous macrolides, were prepared and bio-evaluated as inhibitors of K562 leukemia cells. Interesting preliminary SAR (structure activity relationship) information was obtained from the products. The most sensitive functionalities were the 16,17-vinyl epoxide in both salarins, the triacylamino group in salarin A and the oxazole in salarin C (less sensitive). Regioselectivity of reactions was also found for tulearin A. Full article
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Open AccessArticle Penicillinolide A: A New Anti-Inflammatory Metabolite from the Marine Fungus Penicillium sp. SF-5292
Mar. Drugs 2013, 11(11), 4510-4526; doi:10.3390/md11114510
Received: 9 October 2013 / Revised: 30 October 2013 / Accepted: 31 October 2013 / Published: 12 November 2013
Cited by 12 | PDF Full-text (639 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In the course of studies on bioactive metabolites from marine fungi, a new 10-membered lactone, named penicillinolide A (1) was isolated from the organic extract of Penicillium sp. SF-5292 as a potential anti-inflammatory compound. The structure of penicillinolide A (1
[...] Read more.
In the course of studies on bioactive metabolites from marine fungi, a new 10-membered lactone, named penicillinolide A (1) was isolated from the organic extract of Penicillium sp. SF-5292 as a potential anti-inflammatory compound. The structure of penicillinolide A (1) was mainly determined by analysis of NMR and MS data and Mosher’s method. Penicillinolide A (1) inhibited the production of NO and PGE2 due to inhibition of the expression of iNOS and COX-2. Penicillinolide A (1) also reduced TNF-α, IL-1β and IL-6 production, and these anti-inflammatory effects were shown to be correlated with the suppression of the phosphorylation and degradation of IκB-α, NF-κB nuclear translocation, and NF-κB DNA binding activity. In addition, using inhibitor tin protoporphyrin (SnPP), a competitive inhibitor of HO activity, it was verified that the inhibitory effects of compound 1 on the production of pro-inflammatory mediators and NF-κB DNA binding activity were partially associated with HO-1 expression through Nrf2 nuclear translocation. Full article
Open AccessArticle Design and Synthesis of Pro-Apoptotic Compounds Inspired by Diatom Oxylipins
Mar. Drugs 2013, 11(11), 4527-4543; doi:10.3390/md11114527
Received: 5 September 2013 / Revised: 29 October 2013 / Accepted: 1 November 2013 / Published: 13 November 2013
Cited by 2 | PDF Full-text (614 KB) | HTML Full-text | XML Full-text
Abstract
Oxylipins are a large and diverse family of fatty acid derivatives exhibiting different levels of oxidation of the carbon chain. They are involved in many biological functions in mammals, plants and diatoms. In this last group of organisms, they are suggested to play
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Oxylipins are a large and diverse family of fatty acid derivatives exhibiting different levels of oxidation of the carbon chain. They are involved in many biological functions in mammals, plants and diatoms. In this last group of organisms, they are suggested to play a role in the reproductive failure of copepod predators, showing clear pro-apoptotic effects on newborn nauplii. In this work, these compounds were tested for the ability to induce mitotic arrest in sea urchin embryos. We show for the first time that oxylipins have an increased efficacy in their corresponding methylated form. Natural oxylipins were also used as an inspiration for the rational design and synthesis of stable chemical analogs with apoptotic activity against tumor cell lines. This approach led to the synthesis of the linear C15-ketol (22) that was shown to induce apoptosis in human leukemia U-937 cells. These results are proof of the concept of the use of eco-physiological considerations as a platform to guide the search for novel drug candidates. Full article
Open AccessArticle Antibacterial Activity of Long-Chain Polyunsaturated Fatty Acids against Propionibacterium acnes and Staphylococcus aureus
Mar. Drugs 2013, 11(11), 4544-4557; doi:10.3390/md11114544
Received: 24 September 2013 / Revised: 31 October 2013 / Accepted: 4 November 2013 / Published: 13 November 2013
Cited by 12 | PDF Full-text (593 KB) | HTML Full-text | XML Full-text
Abstract
New compounds are needed to treat acne and superficial infections caused by Propionibacterium acnes and Staphylococcus aureus due to the reduced effectiveness of agents used at present. Long-chain polyunsaturated fatty acids (LC-PUFAs) are attracting attention as potential new topical treatments for Gram-positive infections
[...] Read more.
New compounds are needed to treat acne and superficial infections caused by Propionibacterium acnes and Staphylococcus aureus due to the reduced effectiveness of agents used at present. Long-chain polyunsaturated fatty acids (LC-PUFAs) are attracting attention as potential new topical treatments for Gram-positive infections due to their antimicrobial potency and anti-inflammatory properties. This present study aimed to investigate the antimicrobial effects of six LC-PUFAs against P. acnes and S. aureus to evaluate their potential to treat infections caused by these pathogens. Minimum inhibitory concentrations were determined against P. acnes and S. aureus, and the LC-PUFAs were found to inhibit bacterial growth at 32–1024 mg/L. Generally, P. acnes was more susceptible to the growth inhibitory actions of LC-PUFAs, but these compounds were bactericidal only for S. aureus. This is the first report of antibacterial activity attributed to 15-hydroxyeicosapentaenoic acid (15-OHEPA) and 15-hydroxyeicosatrienoic acid (HETrE), while the anti-P. acnes effects of the six LC-PUFAs used herein are novel observations. During exposure to the LC-PUFAs, S. aureus cells were killed within 15–30 min. Checkerboard assays demonstrated that the LC-PUFAs did not antagonise the antimicrobial potency of clinical agents used presently against P. acnes and S. aureus. However, importantly, synergistic interactions against S. aureus were detected for combinations of benzoyl peroxide with 15-OHEPA, dihomo-γ-linolenic acid (DGLA) and HETrE; and neomycin with 15-OHEPA, DGLA, eicosapentaenoic acid, γ-linolenic acid and HETrE. In conclusion, LC-PUFAs warrant further evaluation as possible new agents to treat skin infections caused by P. acnes and S. aureus, especially in synergistic combinations with antimicrobial agents already used clinically. Full article
(This article belongs to the Special Issue Marine Fatty Acids-2013)
Open AccessArticle Improvement of Neutral Lipid and Polyunsaturated Fatty Acid Biosynthesis by Overexpressing a Type 2 Diacylglycerol Acyltransferase in Marine Diatom Phaeodactylum tricornutum
Mar. Drugs 2013, 11(11), 4558-4569; doi:10.3390/md11114558
Received: 26 September 2013 / Revised: 31 October 2013 / Accepted: 7 November 2013 / Published: 13 November 2013
Cited by 33 | PDF Full-text (969 KB) | HTML Full-text | XML Full-text
Abstract
Microalgae have been emerging as an important source for the production of bioactive compounds. Marine diatoms can store high amounts of lipid and grow quite quickly. However, the genetic and biochemical characteristics of fatty acid biosynthesis in diatoms remain unclear. Glycerophospholipids are integral
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Microalgae have been emerging as an important source for the production of bioactive compounds. Marine diatoms can store high amounts of lipid and grow quite quickly. However, the genetic and biochemical characteristics of fatty acid biosynthesis in diatoms remain unclear. Glycerophospholipids are integral as structural and functional components of cellular membranes, as well as precursors of various lipid mediators. In addition, diacylglycerol acyltransferase (DGAT) is a key enzyme that catalyzes the last step of triacylglyceride (TAG) biosynthesis. However, a comprehensive sequence-structure and functional analysis of DGAT in diatoms is lacking. In this study, an isoform of diacylglycerol acyltransferase type 2 of the marine diatom Phaeodactylum tricornutum was characterized. Surprisingly, DGAT2 overexpression in P. tricornutum stimulated more oil bodies, and the neutral lipid content increased by 35%. The fatty acid composition showed a significant increase in the proportion of polyunsaturated fatty acids; in particular, EPA was increased by 76.2%. Moreover, the growth rate of transgenic microalgae remained similar, thereby maintaining a high biomass. Our results suggest that increased DGAT2 expression could alter fatty acid profile in the diatom, and the results thus represent a valuable strategy for polyunsaturated fatty acid production by genetic manipulation. Full article
(This article belongs to the Special Issue Marine Fatty Acids-2013)
Open AccessArticle Ophiobolin-O Reverses Adriamycin Resistance via Cell Cycle Arrest and Apoptosis Sensitization in Adriamycin-Resistant Human Breast Carcinoma (MCF-7/ADR) Cells
Mar. Drugs 2013, 11(11), 4570-4584; doi:10.3390/md11114570
Received: 30 August 2013 / Revised: 20 October 2013 / Accepted: 24 October 2013 / Published: 14 November 2013
Cited by 11 | PDF Full-text (1301 KB) | HTML Full-text | XML Full-text
Abstract
Multidrug-resistance is a major obstacle facing cancer chemotherapy. This paper demonstrates that novel compound Ophiobolin-O reverses MCF-7/ADR resistance to adriamycin (ADM). The IC50 of ADM treated MCF-7 cells was 2.02 ± 0.05 µM and 74.00 ± 0.18 µM treated MCF-7/ADR cells, about
[...] Read more.
Multidrug-resistance is a major obstacle facing cancer chemotherapy. This paper demonstrates that novel compound Ophiobolin-O reverses MCF-7/ADR resistance to adriamycin (ADM). The IC50 of ADM treated MCF-7 cells was 2.02 ± 0.05 µM and 74.00 ± 0.18 µM treated MCF-7/ADR cells, about 37-fold, compared to the former. However, 0.1 µM Ophiobolin-O (less than 20% inhibition concentration) combined with ADM caused the decreased IC50 of ADM to 6.67 ± 0.98 µM, indicating it reversed ADM resistance of MCF-7/ADR cells (11-fold). Furthermore, Ophiobolin-O increased ADM-induced mitochondrial pathway apoptosis and G2/M phase arrest, which is partly due to the elevation level of ROS in MCF-7/ADR cells. As we described in this paper, the reversal effect of Ophiobolin-O may be due to the reduction of resistance-related protein P-Glycoprotein (P-gp, also known as MDR1) through inhibiting the activity of the multidrug resistance 1 (MDR1) gene promoter, which makes MCF-7/ADR cells more sensitive to ADM treatment. Assays in nude mice also showed that the combination of ADM and Ophiobolin-O significantly improved the effect of ADM. Full article
Open AccessArticle Discovery of New Eunicellin-Based Diterpenoids from a Formosan Soft Coral Cladiella sp.
Mar. Drugs 2013, 11(11), 4585-4593; doi:10.3390/md11114585
Received: 26 August 2013 / Revised: 17 October 2013 / Accepted: 31 October 2013 / Published: 14 November 2013
Cited by 11 | PDF Full-text (373 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A new eunicellin diterpenoid, cladieunicellin I (1), and a new natural eunicellin, litophynin I diacetate (2), were isolated from a Formosan soft coral identified as Cladiella sp. The structures of eunicellins 1 and 2 were elucidated by spectroscopic methods
[...] Read more.
A new eunicellin diterpenoid, cladieunicellin I (1), and a new natural eunicellin, litophynin I diacetate (2), were isolated from a Formosan soft coral identified as Cladiella sp. The structures of eunicellins 1 and 2 were elucidated by spectroscopic methods and by comparison of the spectral data with those of related analogues. Eunicellin 1 exhibited significant cytotoxicity toward the DLD-1 human colorectal adenocarcinoma cells. Full article
Open AccessArticle Simultaneous Extraction and Depolymerization of Fucoidan from Sargassum muticum in Aqueous Media
Mar. Drugs 2013, 11(11), 4612-4627; doi:10.3390/md11114612
Received: 9 October 2013 / Revised: 4 November 2013 / Accepted: 5 November 2013 / Published: 21 November 2013
Cited by 15 | PDF Full-text (618 KB) | HTML Full-text | XML Full-text
Abstract
The biomass components of the invasive seaweed Sargassum muticum were fractionated to allow their separate valorization. S. muticum (Sm) and the solid residue remaining after alginate extraction of this seaweed (AESm) were processed with hot, compressed water (hydrothermal processing) to assess the effects
[...] Read more.
The biomass components of the invasive seaweed Sargassum muticum were fractionated to allow their separate valorization. S. muticum (Sm) and the solid residue remaining after alginate extraction of this seaweed (AESm) were processed with hot, compressed water (hydrothermal processing) to assess the effects of temperature on fucoidan solubilization. Fucose-containing oligosaccharides were identified as reaction products. Operating under optimal conditions (170 °C), up to 62 and 85 wt% of the dry mass of Sm and AESm were solubilized, respectively. The reaction media were subjected to precipitation, nanofiltration and freeze-drying. The dried products contained 50% and 85% of the fucoidan present in Sm and AESm, respectively; together with other components such as phenolics and inorganic components. The saccharidic fraction, accounting for up to 35% of the dried extracts, contained fucose as the main sugar, and also galactose, xylose, glucose and mannose. The concentrates were characterized for antioxidant activity using the TEAC assay. Full article
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Open AccessArticle Antiviral Sulfoquinovosyldiacylglycerols (SQDGs) from the Brazilian Brown Seaweed Sargassum vulgare
Mar. Drugs 2013, 11(11), 4628-4640; doi:10.3390/md11114628
Received: 17 September 2013 / Revised: 29 October 2013 / Accepted: 4 November 2013 / Published: 21 November 2013
Cited by 13 | PDF Full-text (766 KB) | HTML Full-text | XML Full-text
Abstract
Total lipids from the Brazilian brown seaweed Sargassum vulgare were extracted with chloroform/methanol 2:1 and 1:2 (v/v) at room temperature. After performing Folch partition of the crude lipid extract, the lipids recovered from the Folch lower layer were fractionated on a silica gel
[...] Read more.
Total lipids from the Brazilian brown seaweed Sargassum vulgare were extracted with chloroform/methanol 2:1 and 1:2 (v/v) at room temperature. After performing Folch partition of the crude lipid extract, the lipids recovered from the Folch lower layer were fractionated on a silica gel column eluted with chloroform, acetone and methanol. The fraction eluted with methanol, presented a strong orcinol-positive band characteristic of the presence of sulfatides when examined by TLC. This fraction was then purified by two successive silica gel column chromatography giving rise to fractions F4I86 and F4II90 that exhibited strong activity against herpes simplex virus type 1 and 2. The chemical structures present in both fractions were elucidated by ESI-MS and 1H/13C NMR analysis HSQC fingerprints based on their tandem–MS behavior as Sulfoquinovosyldiacylglycerols  (SQDGs). The main SQDG present in both fractions and responsible for the anti-herpes activity observed was identified as 1,2-di-O-palmitoyl-3-O-(6-sulfo-α-d-quinovopyranosyl)-glycerol. Full article
(This article belongs to the Special Issue Marine Fatty Acids-2013)
Open AccessArticle Isolation and Characterization of Collagen and Antioxidant Collagen Peptides from Scales of Croceine Croaker (Pseudosciaena crocea)
Mar. Drugs 2013, 11(11), 4641-4661; doi:10.3390/md11114641
Received: 28 August 2013 / Revised: 7 November 2013 / Accepted: 7 November 2013 / Published: 21 November 2013
Cited by 13 | PDF Full-text (521 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Acid soluble collagen (ASC) from scales of croceine croaker (ASC-C) was successfully isolated with the yield of 0.37% ± 0.08% (dry weight basis), and characterized as type I collagen on the basis of amino acid analysis and electrophoretic pattern. The antioxidant hydrolysate of
[...] Read more.
Acid soluble collagen (ASC) from scales of croceine croaker (ASC-C) was successfully isolated with the yield of 0.37% ± 0.08% (dry weight basis), and characterized as type I collagen on the basis of amino acid analysis and electrophoretic pattern. The antioxidant hydrolysate of ASC-C (ACH) was prepared through a two-stage in vitro digestion (4-h trypsin followed by 4-h pepsin), and three antioxidant peptides (ACH-P1, ACH-P2, and ACH-P3) were further isolated from ACH using ultrafiltration, gel chromatography, and RP-HPLC, and their amino acid sequences were identified as GFRGTIGLVG (ACH-P1), GPAGPAG (ACH-P2), and GFPSG (ACH-P3). ACH-P1, ACH-P2, and ACH-P3 showed good scavenging activities on hydroxyl radical (IC50 0.293, 0.240, and 0.107 mg/mL, respectively), DPPH radical (IC50 1.271, 0.675, and 0.283 mg/mL, respectively), superoxide radical (IC50 0.463, 0.099, and 0.151 mg/mL, respectively), and ABTS radical (IC50 0.421, 0.309, and 0.210 mg/mL, respectively). ACH-P3 was also effectively against lipid peroxidation in the model system. The antioxidant activities of three collagen peptides were due to the presence of hydrophobic amino acid residues within the peptide sequences. The collagen peptides might be used as antioxidant for the therapy of diseases associated with oxidative stress, or reducing oxidative changes during storage. Full article

Review

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Open AccessReview Okadaic Acid: More than a Diarrheic Toxin
Mar. Drugs 2013, 11(11), 4328-4349; doi:10.3390/md11114328
Received: 15 July 2013 / Revised: 8 October 2013 / Accepted: 23 October 2013 / Published: 31 October 2013
Cited by 26 | PDF Full-text (394 KB) | HTML Full-text | XML Full-text
Abstract
Okadaic acid (OA) is one of the most frequent and worldwide distributed marine toxins. It is easily accumulated by shellfish, mainly bivalve mollusks and fish, and, subsequently, can be consumed by humans causing alimentary intoxications. OA is the main representative diarrheic shellfish poisoning
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Okadaic acid (OA) is one of the most frequent and worldwide distributed marine toxins. It is easily accumulated by shellfish, mainly bivalve mollusks and fish, and, subsequently, can be consumed by humans causing alimentary intoxications. OA is the main representative diarrheic shellfish poisoning (DSP) toxin and its ingestion induces gastrointestinal symptoms, although it is not considered lethal. At the molecular level, OA is a specific inhibitor of several types of serine/threonine protein phosphatases and a tumor promoter in animal carcinogenesis experiments. In the last few decades, the potential toxic effects of OA, beyond its role as a DSP toxin, have been investigated in a number of studies. Alterations in DNA and cellular components, as well as effects on immune and nervous system, and even on embryonic development, have been increasingly reported. In this manuscript, results from all these studies are compiled and reviewed to clarify the role of this toxin not only as a DSP inductor but also as cause of alterations at the cellular and molecular levels, and to highlight the relevance of biomonitoring its effects on human health. Despite further investigations are required to elucidate OA mechanisms of action, toxicokinetics, and harmful effects, there are enough evidences illustrating its toxicity, not related to DSP induction, and, consequently, supporting a revision of the current regulation on OA levels in food. Full article
(This article belongs to the Special Issue Cytogenetic and Molecular Effects of Marine Compounds)
Open AccessReview Phylogeny and Biogeography of Cyanobacteria and Their Produced Toxins
Mar. Drugs 2013, 11(11), 4350-4369; doi:10.3390/md11114350
Received: 16 July 2013 / Revised: 29 August 2013 / Accepted: 9 October 2013 / Published: 1 November 2013
Cited by 10 | PDF Full-text (404 KB) | HTML Full-text | XML Full-text
Abstract
Phylogeny is an evolutionary reconstruction of the past relationships of DNA or protein sequences and it can further be used as a tool to assess population structuring, genetic diversity and biogeographic patterns. In the microbial world, the concept that everything is everywhere is
[...] Read more.
Phylogeny is an evolutionary reconstruction of the past relationships of DNA or protein sequences and it can further be used as a tool to assess population structuring, genetic diversity and biogeographic patterns. In the microbial world, the concept that everything is everywhere is widely accepted. However, it is much debated whether microbes are easily dispersed globally or whether they, like many macro-organisms, have historical biogeographies. Biogeography can be defined as the science that documents the spatial and temporal distribution of a given taxa in the environment at local, regional and continental scales. Speciation, extinction and dispersal are proposed to explain the generation of biogeographic patterns. Cyanobacteria are a diverse group of microorganisms that inhabit a wide range of ecological niches and are well known for their toxic secondary metabolite production. Knowledge of the evolution and dispersal of these microorganisms is still limited, and further research to understand such topics is imperative. Here, we provide a compilation of the most relevant information regarding these issues to better understand the present state of the art as a platform for future studies, and we highlight examples of both phylogenetic and biogeographic studies in non-symbiotic cyanobacteria and cyanotoxins. Full article
(This article belongs to the Special Issue Compounds from Cyanobacteria)
Open AccessReview Bivalve Omics: State of the Art and Potential Applications for the Biomonitoring of Harmful Marine Compounds
Mar. Drugs 2013, 11(11), 4370-4389; doi:10.3390/md11114370
Received: 10 July 2013 / Revised: 27 September 2013 / Accepted: 9 October 2013 / Published: 1 November 2013
Cited by 27 | PDF Full-text (964 KB) | HTML Full-text | XML Full-text
Abstract
The extraordinary progress experienced by sequencing technologies and bioinformatics has made the development of omic studies virtually ubiquitous in all fields of life sciences nowadays. However, scientific attention has been quite unevenly distributed throughout the different branches of the tree of life, leaving
[...] Read more.
The extraordinary progress experienced by sequencing technologies and bioinformatics has made the development of omic studies virtually ubiquitous in all fields of life sciences nowadays. However, scientific attention has been quite unevenly distributed throughout the different branches of the tree of life, leaving molluscs, one of the most diverse animal groups, relatively unexplored and without representation within the narrow collection of well established model organisms. Within this Phylum, bivalve molluscs play a fundamental role in the functioning of the marine ecosystem, constitute very valuable commercial resources in aquaculture, and have been widely used as sentinel organisms in the biomonitoring of marine pollution. Yet, it has only been very recently that this complex group of organisms became a preferential subject for omic studies, posing new challenges for their integrative characterization. The present contribution aims to give a detailed insight into the state of the art of the omic studies and functional information analysis of bivalve molluscs, providing a timely perspective on the available data resources and on the current and prospective applications for the biomonitoring of harmful marine compounds. Full article
(This article belongs to the Special Issue Cytogenetic and Molecular Effects of Marine Compounds)
Figures

Open AccessReview Bioprospecting Marine Plankton
Mar. Drugs 2013, 11(11), 4594-4611; doi:10.3390/md11114594
Received: 10 July 2013 / Revised: 6 September 2013 / Accepted: 9 October 2013 / Published: 14 November 2013
Cited by 9 | PDF Full-text (892 KB) | HTML Full-text | XML Full-text
Abstract
The ocean dominates the surface of our planet and plays a major role in regulating the biosphere. For example, the microscopic photosynthetic organisms living within provide 50% of the oxygen we breathe, and much of our food and mineral resources are extracted from
[...] Read more.
The ocean dominates the surface of our planet and plays a major role in regulating the biosphere. For example, the microscopic photosynthetic organisms living within provide 50% of the oxygen we breathe, and much of our food and mineral resources are extracted from the ocean. In a time of ecological crisis and major changes in our society, it is essential to turn our attention towards the sea to find additional solutions for a sustainable future. Remarkably, while we are overexploiting many marine resources, particularly the fisheries, the planktonic compartment composed of zooplankton, phytoplankton, bacteria and viruses, represents 95% of marine biomass and yet the extent of its diversity remains largely unknown and underexploited. Consequently, the potential of plankton as a bioresource for humanity is largely untapped. Due to their diverse evolutionary backgrounds, planktonic organisms offer immense opportunities: new resources for medicine, cosmetics and food, renewable energy, and long-term solutions to mitigate climate change. Research programs aiming to exploit culture collections of marine micro-organisms as well as to prospect the huge resources of marine planktonic biodiversity in the oceans are now underway, and several bioactive extracts and purified compounds have already been identified. This review will survey and assess the current state-of-the-art and will propose methodologies to better exploit the potential of marine plankton for drug discovery and for dermocosmetics. Full article
(This article belongs to the collection Bioactive Compounds from Marine Plankton)
Open AccessReview Pathways of Lipid Metabolism in Marine Algae, Co-Expression Network, Bottlenecks and Candidate Genes for Enhanced Production of EPA and DHA in Species of Chromista
Mar. Drugs 2013, 11(11), 4662-4697; doi:10.3390/md11114662
Received: 24 September 2013 / Revised: 5 November 2013 / Accepted: 7 November 2013 / Published: 22 November 2013
Cited by 30 | PDF Full-text (1275 KB) | HTML Full-text | XML Full-text
Abstract
The importance of n-3 long chain polyunsaturated fatty acids (LC-PUFAs) for human health has received more focus the last decades, and the global consumption of n-3 LC-PUFA has increased. Seafood, the natural n-3 LC-PUFA source, is harvested beyond a sustainable
[...] Read more.
The importance of n-3 long chain polyunsaturated fatty acids (LC-PUFAs) for human health has received more focus the last decades, and the global consumption of n-3 LC-PUFA has increased. Seafood, the natural n-3 LC-PUFA source, is harvested beyond a sustainable capacity, and it is therefore imperative to develop alternative n-3 LC-PUFA sources for both eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3). Genera of algae such as Nannochloropsis, Schizochytrium, Isochrysis and Phaedactylum within the kingdom Chromista have received attention due to their ability to produce n-3 LC-PUFAs. Knowledge of LC-PUFA synthesis and its regulation in algae at the molecular level is fragmentary and represents a bottleneck for attempts to enhance the n-3 LC-PUFA levels for industrial production. In the present review, Phaeodactylum tricornutum has been used to exemplify the synthesis and compartmentalization of n-3 LC-PUFAs. Based on recent transcriptome data a co-expression network of 106 genes involved in lipid metabolism has been created. Together with recent molecular biological and metabolic studies, a model pathway for n-3 LC-PUFA synthesis in P. tricornutum has been proposed, and is compared to industrialized species of Chromista. Limitations of the n-3 LC-PUFA synthesis by enzymes such as thioesterases, elongases, acyl-CoA synthetases and acyltransferases are discussed and metabolic bottlenecks are hypothesized such as the supply of the acetyl-CoA and NADPH. A future industrialization will depend on optimization of chemical compositions and increased biomass production, which can be achieved by exploitation of the physiological potential, by selective breeding and by genetic engineering. Full article
(This article belongs to the Special Issue Marine Fatty Acids-2013)

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