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Mar. Drugs, Volume 16, Issue 9 (September 2018)

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Open AccessArticle Cloning of the Bisucaberin B Biosynthetic Gene Cluster from the Marine Bacterium Tenacibaculum mesophilum, and Heterologous Production of Bisucaberin B
Mar. Drugs 2018, 16(9), 342; https://doi.org/10.3390/md16090342 (registering DOI)
Received: 24 August 2018 / Revised: 12 September 2018 / Accepted: 15 September 2018 / Published: 19 September 2018
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Abstract
The biosynthetic gene cluster for bisucaberin B (1, bsb gene cluster), an N-hydroxy-N-succinyl diamine (HSD)-based siderophore, was cloned from the marine bacterium Tenacibaculum mesophilum, originated from a marine sponge. The bsb gene cluster consists of six open
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The biosynthetic gene cluster for bisucaberin B (1, bsb gene cluster), an N-hydroxy-N-succinyl diamine (HSD)-based siderophore, was cloned from the marine bacterium Tenacibaculum mesophilum, originated from a marine sponge. The bsb gene cluster consists of six open reading frames (ORFs), in contrast to the four ORFs typically seen in biosynthetic gene clusters of the related molecules. Heterologous expression of the key enzyme, BsbD2, which is responsible for the final biosynthetic step of 1 resulted in production of bisucaberin B (1), but not bisucaberin (2) a macrocyclic counterpart of 1. To date, numbers of related enzymes producing macrocyclic analogues have been reported, but this work represents the first example of the HSD-based siderophore biosynthetic enzyme which exclusively produces a linear molecule rather than macrocyclic counterparts. Full article
(This article belongs to the Special Issue Marine Natural Products Discovery: In Honor of Late Prof. Tatsuo Higa)
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Open AccessArticle Stress-Induced Mucus Secretion and Its Composition by a Combination of Proteomics and Metabolomics of the Jellyfish Aurelia coerulea
Mar. Drugs 2018, 16(9), 341; https://doi.org/10.3390/md16090341
Received: 24 August 2018 / Revised: 5 September 2018 / Accepted: 9 September 2018 / Published: 18 September 2018
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Abstract
Background: Jellyfish respond quickly to external stress that stimulates mucus secretion as a defense. Neither the composition of secreted mucus nor the process of secretion are well understood. Methods: Aurelia coerulea jellyfish were stimulated by removing them from environmental seawater. Secreted mucus and
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Background: Jellyfish respond quickly to external stress that stimulates mucus secretion as a defense. Neither the composition of secreted mucus nor the process of secretion are well understood. Methods: Aurelia coerulea jellyfish were stimulated by removing them from environmental seawater. Secreted mucus and tissue samples were then collected within 60 min, and analyzed by a combination of proteomics and metabolomics using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) and ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS), respectively. Results: Two phases of sample collection displayed a quick decrease in volume, followed by a gradual increase. A total of 2421 and 1208 proteins were identified in tissue homogenate and secreted mucus, respectively. Gene Ontology (GO) analysis showed that the mucus-enriched proteins are mainly located in extracellular or membrane-associated regions, while the tissue-enriched proteins are distributed throughout intracellular compartments. Tryptamine, among 16 different metabolites, increased with the largest-fold change value of 7.8 in mucus, which is consistent with its involvement in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway ‘tryptophan metabolism’. We identified 11 metalloproteinases, four serpins, three superoxide dismutases and three complements, and their presence was speculated to be related to self-protective defense. Conclusions: Our results provide a composition profile of proteins and metabolites in stress-induced mucus and tissue homogenate of A. coerulea. This provides insight for the ongoing endeavors to discover novel bioactive compounds. The large increase of tryptamine in mucus may indicate a strong stress response when jellyfish were taken out of seawater and the active self-protective components such as enzymes, serpins and complements potentially play a key role in innate immunity of jellyfish. Full article
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Open AccessReview Bioactive Compounds from Marine Organisms: Potential for Bone Growth and Healing
Mar. Drugs 2018, 16(9), 340; https://doi.org/10.3390/md16090340
Received: 8 August 2018 / Revised: 10 September 2018 / Accepted: 11 September 2018 / Published: 18 September 2018
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Abstract
Marine organisms represent a highly diverse reserve of bioactives which could aid in the treatment of a wide range of diseases, including various musculoskeletal conditions. Osteoporosis in particular would benefit from a novel and effective marine-based treatment, due to its large disease burden
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Marine organisms represent a highly diverse reserve of bioactives which could aid in the treatment of a wide range of diseases, including various musculoskeletal conditions. Osteoporosis in particular would benefit from a novel and effective marine-based treatment, due to its large disease burden and the inefficiencies of current treatment options. Osteogenic bioactives have been isolated from many marine organisms, including nacre powder derived from molluscan shells and fucoidan—the sulphated polysaccharide commonly sourced from brown macroalgae. Such extracts and compounds are known to have a range of osteogenic effects, including stimulation of osteoblast activity and mineralisation, as well as suppression of osteoclast resorption. This review describes currently known soluble osteogenic extracts and compounds from marine invertebrates and algae, and assesses their preclinical potential. Full article
(This article belongs to the Special Issue Marine Organisms for Bone Regeneration)
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Open AccessReview Natural Product Chemistry of Gorgonian Corals of Genus Junceella–Part III
Mar. Drugs 2018, 16(9), 339; https://doi.org/10.3390/md16090339
Received: 28 August 2018 / Revised: 10 September 2018 / Accepted: 15 September 2018 / Published: 17 September 2018
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Abstract
The structures, names, bioactivities, and references of 82 natural products, including 48 new metabolites, purified from the gorgonian corals belonging to the genus Junceella are described in this review. All compounds mentioned in this review were obtained from Junceella fragilis, Junceella gemmacea
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The structures, names, bioactivities, and references of 82 natural products, including 48 new metabolites, purified from the gorgonian corals belonging to the genus Junceella are described in this review. All compounds mentioned in this review were obtained from Junceella fragilis, Junceella gemmacea, Junceella juncea, and Junceella sp., collected from tropical Indo-Pacific Ocean. Some of these compounds exhibited potential biomedical activities. Full article
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Open AccessCommunication Total Synthesis of the Highly N-Methylated Peptides Carmabin A and Dragomabin
Mar. Drugs 2018, 16(9), 338; https://doi.org/10.3390/md16090338
Received: 28 August 2018 / Revised: 7 September 2018 / Accepted: 12 September 2018 / Published: 17 September 2018
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Abstract
The first total synthesis of carmabin A and dragomabin was achieved at 52.3 mg and 43.8 mg scale, respectively. The synthesis led to determination of the configuration of carmabin A and reassignment of the configuration of dragomabin at the stereogenic centre on the
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The first total synthesis of carmabin A and dragomabin was achieved at 52.3 mg and 43.8 mg scale, respectively. The synthesis led to determination of the configuration of carmabin A and reassignment of the configuration of dragomabin at the stereogenic centre on the alkyne-bearing fragment. Full article
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Open AccessArticle Isolation, Characterization, and Pharmaceutical Applications of an Exopolysaccharide from Aerococcus Uriaeequi
Mar. Drugs 2018, 16(9), 337; https://doi.org/10.3390/md16090337
Received: 28 August 2018 / Revised: 13 September 2018 / Accepted: 13 September 2018 / Published: 16 September 2018
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Abstract
Many marine bacteria secrete exopolysaccharides (EPSs), which are made up of a substantial component of the macro-molecules surrounding cells. Recently, the wide demand for EPSs for food, cosmetics, pharmaceutical and other applications has led to great interest in them. In this study, an
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Many marine bacteria secrete exopolysaccharides (EPSs), which are made up of a substantial component of the macro-molecules surrounding cells. Recently, the wide demand for EPSs for food, cosmetics, pharmaceutical and other applications has led to great interest in them. In this study, an EPS produced by marine bacteria Aerococcus uriaeequi HZ strains (EPS-A) was isolated and purified to examine its structure and biological function. The molecular weight of EPS-A analyzed by high-performance liquid gel filtration chromatography (HPGFC) is found to have a number average of 2.22 × 105 and weight average of 2.84 × 105, respectively. High-performance liquid chromatography (HPLC) and Fourier-transform–infrared (FT–IR) analysis indicate that EPS-A was a polysaccharide composed of glucose and a little mannose. In addition, the flocculating rate of sewage of EPS-A was 79.90%. The hygroscopicity studies showed that hygroscopicity of EPS-A was higher than chitosan but lower than that of sodium hyaluronate. The moisture retention of EPS-A showed similar retention activity to both chitosan and sodium hyaluronate. EPS-A also can scavenge free radicals including both OH• free radical and O2 free radical and the activity to O2 free radical is similar to vitamin C. Safety assessment on mice indicated that the EPS-A is safe for external use and oral administration. EPS-A has great potential for applications in medicine due to its characteristics mentioned above. Full article
(This article belongs to the collection Marine Polysaccharides) Printed Edition available
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Open AccessReview UV-Protective Compounds in Marine Organisms from the Southern Ocean
Mar. Drugs 2018, 16(9), 336; https://doi.org/10.3390/md16090336
Received: 12 July 2018 / Revised: 3 September 2018 / Accepted: 12 September 2018 / Published: 14 September 2018
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Abstract
Solar radiation represents a key abiotic factor in the evolution of life in the oceans. In general, marine, biota—particularly in euphotic and dysphotic zones—depends directly or indirectly on light, but ultraviolet radiation (UV-R) can damage vital molecular machineries. UV-R induces the formation of
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Solar radiation represents a key abiotic factor in the evolution of life in the oceans. In general, marine, biota—particularly in euphotic and dysphotic zones—depends directly or indirectly on light, but ultraviolet radiation (UV-R) can damage vital molecular machineries. UV-R induces the formation of reactive oxygen species (ROS) and impairs intracellular structures and enzymatic reactions. It can also affect organismal physiologies and eventually alter trophic chains at the ecosystem level. In Antarctica, physical drivers, such as sunlight, sea-ice, seasonality and low temperature are particularly influencing as compared to other regions. The springtime ozone depletion over the Southern Ocean makes organisms be more vulnerable to UV-R. Nonetheless, Antarctic species seem to possess analogous UV photoprotection and repair mechanisms as those found in organisms from other latitudes. The lack of data on species-specific responses towards increased UV-B still limits the understanding about the ecological impact and the tolerance levels related to ozone depletion in this region. The photobiology of Antarctic biota is largely unknown, in spite of representing a highly promising reservoir in the discovery of novel cosmeceutical products. This review compiles the most relevant information on photoprotection and UV-repair processes described in organisms from the Southern Ocean, in the context of this unique marine polar environment. Full article
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Open AccessArticle Cytotoxic Tetrahydroxanthone Dimers from the Mangrove-Associated Fungus Aspergillus versicolor HDN1009
Mar. Drugs 2018, 16(9), 335; https://doi.org/10.3390/md16090335
Received: 22 August 2018 / Revised: 10 September 2018 / Accepted: 12 September 2018 / Published: 14 September 2018
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Abstract
Three new tetrahydroxanthone dimers, 5-epi-asperdichrome (1), versixanthones N (2), and O (3), were isolated from the mangrove-derived fungus Aspergillus versicolor HDN1009. Their structures, including the absolute configurations, were elucidated by NMR, HRMS, and circular dichroism
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Three new tetrahydroxanthone dimers, 5-epi-asperdichrome (1), versixanthones N (2), and O (3), were isolated from the mangrove-derived fungus Aspergillus versicolor HDN1009. Their structures, including the absolute configurations, were elucidated by NMR, HRMS, and circular dichroism (CD) experiments. Among them, compound 1 was the second example of tetrahydroxanthone dimers, which dimerized by a rare diaryl ether linkage and showed promising antibacterial activities against Vibrio parahemolyticus, Bacillus subtilis, Mycobacterium phlei, and Pseudomonas aeruginosa, with MIC values ranging from 100 μM to 200 μM; whilst compounds 2 and 3 exhibited extensive cytotoxicities against five cancer cell lines (HL-60, K562, H1975, MGC803, and HO-8910), with IC50 values ranging from 1.7 μM to 16.1 μM. Full article
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Open AccessArticle Supercritical Carbon Dioxide Extraction of Astaxanthin, Lutein, and Fatty Acids from Haematococcus pluvialis Microalgae
Mar. Drugs 2018, 16(9), 334; https://doi.org/10.3390/md16090334
Received: 12 August 2018 / Revised: 7 September 2018 / Accepted: 11 September 2018 / Published: 13 September 2018
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Abstract
Haematococcus pluvialis microalgae in the red phase can produce significant amounts of astaxanthin, lutein, and fatty acids (FAs), which are valuable antioxidants in nutraceutics and cosmetics. Extraction of astaxanthin, lutein, and FAs from disrupted biomass of the H. pluvialis red phase using carbon
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Haematococcus pluvialis microalgae in the red phase can produce significant amounts of astaxanthin, lutein, and fatty acids (FAs), which are valuable antioxidants in nutraceutics and cosmetics. Extraction of astaxanthin, lutein, and FAs from disrupted biomass of the H. pluvialis red phase using carbon dioxide (CO2) in supercritical fluid extraction (SFE) conditions was investigated using a bench-scale reactor in a semi-batch configuration. In particular, the effect of extraction time (20, 40, 60, 80, and 120 min), CO2 flow rate (3.62 and 14.48 g/min) temperature (50, 65, and 80 °C), and pressure (100, 400, and 550 bar.) was explored. The results show the maximum recovery of astaxanthin and lutein achieved were 98.6% and 52.3%, respectively, at 50 °C and 550 bars, while the maximum recovery of FAs attained was 93.2% at 65 °C and 550 bars. Full article
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Open AccessArticle Influence of Modified Fucoidan and Related Sulfated Oligosaccharides on Hematopoiesis in Cyclophosphamide-Induced Mice
Mar. Drugs 2018, 16(9), 333; https://doi.org/10.3390/md16090333
Received: 21 August 2018 / Revised: 4 September 2018 / Accepted: 8 September 2018 / Published: 13 September 2018
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Abstract
Immunosuppression derived after cytostatics application in cancer chemotherapy is considered as an adverse side effect that leads to deterioration of quality of life and risk of infectious diseases. A linear sulfated (1→3)-α-l-fucan M-Fuc prepared by chemical modification of a fucoidan isolated
[...] Read more.
Immunosuppression derived after cytostatics application in cancer chemotherapy is considered as an adverse side effect that leads to deterioration of quality of life and risk of infectious diseases. A linear sulfated (1→3)-α-l-fucan M-Fuc prepared by chemical modification of a fucoidan isolated from the brown seaweed Chordaria flagelliformis, along with two structurally related synthetic sulfated oligosaccharides, were studied as stimulators of hematopoiesis on a model of cyclophosphamide immunosuppression in mice. Recombinant granulocyte colony-stimulating factor (r G-CSF), which is currently applied in medicine to treat low blood neutrophils, was used as a reference. Polysaccharide M-Fuc and sulfated difucoside DS did not demonstrate significant effect, while sulfated octasaccharide OS showed higher activity than r G-CSF, causing pronounced neutropoiesis stimulation. In addition, production of erythrocytes and platelets was enhanced after the octasaccharide administration. The assessment of populations of cells in blood and bone marrow of mice revealed the difference in mechanisms of action of OS and r G-CSF. Full article
(This article belongs to the Special Issue Marine Polysaccharides in Pharmaceutical Applications)
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Open AccessArticle Characterization of the Microbial Population Inhabiting a Solar Saltern Pond of the Odiel Marshlands (SW Spain)
Mar. Drugs 2018, 16(9), 332; https://doi.org/10.3390/md16090332
Received: 28 June 2018 / Revised: 28 August 2018 / Accepted: 8 September 2018 / Published: 12 September 2018
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Abstract
The solar salterns located in the Odiel marshlands, in southwest Spain, are an excellent example of a hypersaline environment inhabited by microbial populations specialized in thriving under conditions of high salinity, which remains poorly explored. Traditional culture-dependent taxonomic studies have usually under-estimated the
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The solar salterns located in the Odiel marshlands, in southwest Spain, are an excellent example of a hypersaline environment inhabited by microbial populations specialized in thriving under conditions of high salinity, which remains poorly explored. Traditional culture-dependent taxonomic studies have usually under-estimated the biodiversity in saline environments due to the difficulties that many of these species have to grow at laboratory conditions. Here we compare two molecular methods to profile the microbial population present in the Odiel saltern hypersaline water ponds (33% salinity). On the one hand, the construction and characterization of two clone PCR amplified-16S rRNA libraries, and on the other, a high throughput 16S rRNA sequencing approach based on the Illumina MiSeq platform. The results reveal that both methods are comparable for the estimation of major genera, although massive sequencing provides more information about the less abundant ones. The obtained data indicate that Salinibacter ruber is the most abundant genus, followed by the archaea genera, Halorubrum and Haloquadratum. However, more than 100 additional species can be detected by Next Generation Sequencing (NGS). In addition, a preliminary study to test the biotechnological applications of this microbial population, based on its ability to produce and excrete haloenzymes, is shown. Full article
(This article belongs to the Special Issue Genome Mining and Marine Microbial Natural Products)
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Open AccessArticle Stress-Driven Discovery of New Angucycline-Type Antibiotics from a Marine Streptomyces pratensis NA-ZhouS1
Mar. Drugs 2018, 16(9), 331; https://doi.org/10.3390/md16090331
Received: 20 July 2018 / Revised: 31 August 2018 / Accepted: 7 September 2018 / Published: 12 September 2018
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Abstract
Natural products from marine actinomycetes remain an important resource for drug discovery, many of which are produced by the genus, Streptomyces. However, in standard laboratory conditions, specific gene clusters in microbes have long been considered silent or covert. Thus, various stress techniques activated
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Natural products from marine actinomycetes remain an important resource for drug discovery, many of which are produced by the genus, Streptomyces. However, in standard laboratory conditions, specific gene clusters in microbes have long been considered silent or covert. Thus, various stress techniques activated latent gene clusters leading to isolation of potential metabolites. This study focused on the analysis of two new angucycline antibiotics isolated from the culture filtrate of a marine Streptomyces pratensis strain NA-ZhouS1, named, stremycin A (1) and B (2) which were further determined based on spectroscopic techniques such as high resolution time of flight mass spectrometry (HR-TOF-MS), 1D, and 2D nuclear magnetic resonance (NMR) experiments. In addition, four other known compounds, namely, 2-[2-(3,5-dimethyl-2-oxo-cyclohexyl)-6-oxo-tetrahydro-pyran-4yl]-acetamide (3), cyclo[l-(4-hydroxyprolinyl)-l-leucine] (4), 2-methyl-3H-quinazoline-4-one (5), and menthane derivative, 3-(hydroxymethyl)-6-isopropyl-10,12-dioxatricyclo[7.2.1.0]dodec-4-en-8-one (6) were obtained and elucidated by means of 1D NMR spectrometry. Herein, we describe the “Metal Stress Technique” applied in the discovery of angucyclines, a distinctive class of antibiotics that are commonly encoded in microbiomes but have never been reported in “Metal Stress” based discovery efforts. Novel antibiotics 1 and 2 exhibited antimicrobial activities against Pseudomonas aeruginosa, methicillin resistant Staphylococcus aureus (MRSA), Klebsiella pneumonia, and Escherichia coli with equal minimum inhibitory concentration (MIC) values of 16 µg/mL, while these antibiotics showed inhibition against Bacillus subtilis at MIC value of approximately 8–16 µg/mL, respectively. As a result, the outcome of this investigation revealed that metal stress is an effective technique in unlocking the biosynthetic potential and resulting production of novel antibiotics. Full article
(This article belongs to the Special Issue Genome Mining and Marine Microbial Natural Products)
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Open AccessCommunication New Antibacterial Bagremycins F and G from the Marine-Derived Streptomyces sp. ZZ745
Mar. Drugs 2018, 16(9), 330; https://doi.org/10.3390/md16090330
Received: 11 August 2018 / Revised: 30 August 2018 / Accepted: 10 September 2018 / Published: 12 September 2018
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Abstract
As part of our research to discover novel bioactive natural products from marine microorganisms, five bagremycin analogues, including the previously unreported bagremycins F (1) and G (2), were isolated from a marine actinomycete Streptomyces sp. ZZ745. The structures of
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As part of our research to discover novel bioactive natural products from marine microorganisms, five bagremycin analogues, including the previously unreported bagremycins F (1) and G (2), were isolated from a marine actinomycete Streptomyces sp. ZZ745. The structures of these compounds were determined by means of NMR spectroscopic analysis, HRESIMS data, and optical rotation. Both bagremycins F (1) and G (2) showed antibacterial activity against Escherichia coli, with MIC values of 41.8 and 61.7 μM, respectively. Full article
(This article belongs to the Special Issue Natural Products from Marine Actinomycetes)
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Open AccessArticle Highly Substituted Benzophenone Aldehydes and Eremophilane Derivatives from the Deep-Sea Derived Fungus Phomopsis lithocarpus FS508
Mar. Drugs 2018, 16(9), 329; https://doi.org/10.3390/md16090329
Received: 10 August 2018 / Revised: 5 September 2018 / Accepted: 7 September 2018 / Published: 11 September 2018
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Abstract
Five new benzophenone derivatives named tenellones D–H (15), sharing a rare naturally occurring aldehyde functionality in this family, and a new eremophilane derivative named lithocarin A (7), together with two known compounds (6 and 8),
[...] Read more.
Five new benzophenone derivatives named tenellones D–H (15), sharing a rare naturally occurring aldehyde functionality in this family, and a new eremophilane derivative named lithocarin A (7), together with two known compounds (6 and 8), were isolated from the deep marine sediment-derived fungus Phomopsis lithocarpus FS508. All of the structures for these new compounds were fully characterized and established on the basis of extensive spectroscopic interpretation and X-ray crystallographic analysis. Compound 5 exhibited cytotoxic activity against HepG-2 and A549 cell lines with IC50 values of 16.0 and 17.6 μM, respectively. Full article
(This article belongs to the Special Issue Natural Products from Marine Fungi)
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Open AccessArticle Pyropia yezoensis Protein Supplementation Prevents Dexamethasone-Induced Muscle Atrophy in C57BL/6 Mice
Mar. Drugs 2018, 16(9), 328; https://doi.org/10.3390/md16090328
Received: 22 August 2018 / Revised: 5 September 2018 / Accepted: 9 September 2018 / Published: 11 September 2018
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Abstract
We investigated the protective effects of Pyropia yezoensis crude protein (PYCP) against dexamethasone (DEX)-induced myotube atrophy and its underlying mechanisms. DEX (3 mg/kg body weight, intraperitoneal injection) and PYCP (150 and 300 mg/kg body weight, oral) were administrated to mice for 18 days,
[...] Read more.
We investigated the protective effects of Pyropia yezoensis crude protein (PYCP) against dexamethasone (DEX)-induced myotube atrophy and its underlying mechanisms. DEX (3 mg/kg body weight, intraperitoneal injection) and PYCP (150 and 300 mg/kg body weight, oral) were administrated to mice for 18 days, and the effects of PYCP on DEX-induced muscle atrophy were evaluated. Body weight, calf thickness, and gastrocnemius and tibialis anterior muscle weight were significantly decreased by DEX administration (p < 0.05), while PYCP supplementation effectively prevented the DEX-induced decrease in body weight, calf thickness, and muscle weight. PYCP supplementation also attenuated the DEX-induced increase in serum glucose, creatine kinase, and lactate dehydrogenase levels. Additionally, PYCP supplementation reversed DEX-induced muscle atrophy via the regulation of the insulin-like growth factor-I/protein kinase B/rapamycin-sensitive mTOR complex I/forkhead box O signaling pathway. The mechanistic investigation revealed that PYCP inhibited the ubiquitin-proteasome and autophagy-lysosome pathways in DEX-administrated C57BL/6 mice. These findings demonstrated that PYCP increased protein synthesis and decreased protein breakdown to prevent muscle atrophy. Therefore, PYCP supplementation appears to be useful for preventing muscle atrophy. Full article
(This article belongs to the Special Issue The Pharmacological Potential of Marine-Derived Peptides and Proteins)
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Open AccessArticle Gloeothece sp. as a Nutraceutical Source—An Improved Method of Extraction of Carotenoids and Fatty Acids
Mar. Drugs 2018, 16(9), 327; https://doi.org/10.3390/md16090327
Received: 14 August 2018 / Revised: 6 September 2018 / Accepted: 8 September 2018 / Published: 11 September 2018
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Abstract
The nutraceutical potential of microalgae boomed with the exploitation of new species and sustainable extraction systems of bioactive compounds. Thus, a laboratory-made continuous pressurized solvent extraction system (CPSE) was built to optimize the extraction of antioxidant compounds, such as carotenoids and PUFA, from
[...] Read more.
The nutraceutical potential of microalgae boomed with the exploitation of new species and sustainable extraction systems of bioactive compounds. Thus, a laboratory-made continuous pressurized solvent extraction system (CPSE) was built to optimize the extraction of antioxidant compounds, such as carotenoids and PUFA, from a scarcely studied prokaryotic microalga, Gloeothece sp. Following “green chemical principles” and using a GRAS solvent (ethanol), biomass amount, solvent flow-rate/pressure, temperature and solvent volume—including solvent recirculation—were sequentially optimized, with the carotenoids and PUFA content and antioxidant capacity being the objective functions. Gloeothece sp. bioactive compounds were best extracted at 60 °C and 180 bar. Recirculation of solvent in several cycles (C) led to an 11-fold extraction increase of β-carotene (3C) and 7.4-fold extraction of C18:2 n6 t (5C) when compared to operation in open systems. To fully validate results CPSE, this system was compared to a conventional extraction method, ultrasound assisted extraction (UAE). CPSE proved superior in extraction yield, increasing total carotenoids extraction up 3-fold and total PUFA extraction by ca. 1.5-fold, with particular extraction increase of 18:3 n3 by 9.6-fold. Thus, CPSE proved to be an efficient and greener extraction method to obtain bioactive extract from Gloeothece sp. for nutraceutical purposes—with low levels of resources spent, while lowering costs of production and environmental impacts. Full article
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Open AccessArticle Bacillamidins A–G from a Marine-Derived Bacillus pumilus
Mar. Drugs 2018, 16(9), 326; https://doi.org/10.3390/md16090326
Received: 20 August 2018 / Revised: 7 September 2018 / Accepted: 7 September 2018 / Published: 11 September 2018
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Abstract
Seven long-chain amides, including five previously undescribed bacillamidins A–E (15) and two previously reported synthetic analogs, bacillamidins F (6) and G (7), were isolated from extracts of the marine-derived Bacillus pumilus strain RJA1515. The structures
[...] Read more.
Seven long-chain amides, including five previously undescribed bacillamidins A–E (15) and two previously reported synthetic analogs, bacillamidins F (6) and G (7), were isolated from extracts of the marine-derived Bacillus pumilus strain RJA1515. The structures of the new compounds were established by extensive analysis of 1D and 2D nuclear magnetic resonance (NMR) data as well as high resolution mass spectrometry (HRMS), and the absolute configurations of the stereogenic carbons of 14 were established by comparison of the calculated and the experimental electronic circular dichroism (ECD) spectra. The cytotoxic and antimicrobial activities of 17 were evaluated. Full article
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Open AccessArticle Inhibition of Prostate Cancer DU-145 Cells Proliferation by Anthopleura anjunae Oligopeptide (YVPGP) via PI3K/AKT/mTOR Signaling Pathway
Mar. Drugs 2018, 16(9), 325; https://doi.org/10.3390/md16090325
Received: 13 August 2018 / Accepted: 6 September 2018 / Published: 11 September 2018
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Abstract
We investigated the antitumor mechanism of Anthopleura anjunae oligopeptide (AAP-H, YVPGP) in prostate cancer DU-145 cells in vitro and in vivo. Results indicated that AAP-H was nontoxic and exhibited antitumor activities. Cell cycle analysis indicated that AAP-H may arrest DU-145 cells in the
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We investigated the antitumor mechanism of Anthopleura anjunae oligopeptide (AAP-H, YVPGP) in prostate cancer DU-145 cells in vitro and in vivo. Results indicated that AAP-H was nontoxic and exhibited antitumor activities. Cell cycle analysis indicated that AAP-H may arrest DU-145 cells in the S phase. The role of the phosphatidylinositol 3-kinase/protein kinase B/mammalian rapamycin target protein (PI3K/AKT/mTOR) signaling pathway in the antitumor mechanism of APP-H was investigated. Results showed that AAP-H treatment led to dose-dependent reduction in the levels of p-AKT (Ser473), p-PI3K (p85), and p-mTOR (Ser2448), whereas t-AKT and t-PI3K levels remained unaltered compared to the untreated DU-145 cells. Inhibition of PI3K/AKT/mTOR signaling pathway in the DU-145 cells by employing inhibitor LY294002 (10 μM) or rapamycin (20 nM) effectively attenuated AAP-H-induced phosphorylation of AKT and mTOR. At the same time, inhibitor addition further elevated AAP-H-induced cleaved-caspase-3 levels. Furthermore, the effect of AAP-H on tumor growth and the role of the PI3K/AKT/mTOR signaling pathway in nude mouse model were also investigated. Immunohistochemical analysis showed that activated AKT, PI3K, and mTOR levels were reduced in DU-145 xenografts. Western blotting showed that AAP-H treatment resulted in dose-dependent reduction in p-AKT (Ser473), p-PI3K (p85), and p-mTOR (Ser2448) levels, whereas t-AKT and t-PI3K levels remained unaltered. Similarly, Bcl-xL levels decreased, whereas that of Bax increased after AAP-H treatment. AAP-H also increased initiator (caspase 8 and 9) and executor caspase (caspase 3 and 7) levels. Therefore, the antitumor mechanism of APP-H on DU-145 cells may involve regulation of the PI3K/AKT/mTOR signaling pathway, which eventually promotes apoptosis via mitochondrial and death receptor pathways. Thus, the hydrophobic oligopeptide (YVPGP) can be developed as an adjuvant for the prevention or treatment of prostate cancer in the future. Full article
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Open AccessArticle Liposomal Form of the Echinochrome-Carrageenan Complex
Mar. Drugs 2018, 16(9), 324; https://doi.org/10.3390/md16090324
Received: 28 August 2018 / Revised: 6 September 2018 / Accepted: 7 September 2018 / Published: 10 September 2018
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Abstract
Inclusion of drugs in liposomes offers the potential for localized and sustained delivery to mucosal surfaces. The inclusion of the carrageenan matrix with echinochrome A ((Ech)—the active substance of the drug Histochrome) in liposomes was studied. According to the spectral characteristics, Ech was
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Inclusion of drugs in liposomes offers the potential for localized and sustained delivery to mucosal surfaces. The inclusion of the carrageenan matrix with echinochrome A ((Ech)—the active substance of the drug Histochrome) in liposomes was studied. According to the spectral characteristics, Ech was not oxidized and retained stability after encapsulation in the liposomes and the lyophilization process. Loading the liposomes with negatively charged polysaccharide results in the increase in the zeta potential to more negative values (from −14.6 to −24.4 mV), that together with an increasing in the sizes of liposomes (from 125.6 ± 2.5 nm to 159.3 ± 5.8 nm) propose of the formation of the polymer coating on liposomes. The interactions of liposomes with porcine stomach mucin was determined by the DLS and SEM methods. The changes in the zeta-potential and size of the mucin particles were observed as the result of the interaction of liposomes with mucin. To evaluate the mucoadhesive properties of liposomes and the penetration of Ech in the mucosa, a fresh-frozen inner surface of the small intestine of a pig as a model of mucous tissue was used. Polysaccharide-coated liposomes exhibit very good mucoadhesive properties −50% of Ech remains on the mucosa. Full article
(This article belongs to the Special Issue Marine Drugs and Nanomedicine)
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Open AccessArticle Fucoxanthin Inhibits Myofibroblast Differentiation and Extracellular Matrix Production in Nasal Polyp-Derived Fibroblasts via Modulation of Smad-Dependent and Smad-Independent Signaling Pathways
Mar. Drugs 2018, 16(9), 323; https://doi.org/10.3390/md16090323
Received: 14 August 2018 / Revised: 26 August 2018 / Accepted: 8 September 2018 / Published: 10 September 2018
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Abstract
Nasal polyps (NPs) are a multifactorial disorder associated with a chronic inflammatory state of the nasal mucosa. Fucoxanthin (Fx) is a characteristic orange carotenoid obtained from brown algae and has diverse immunological properties. The present study investigated whether Fx inhibits fibrosis-related effects in
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Nasal polyps (NPs) are a multifactorial disorder associated with a chronic inflammatory state of the nasal mucosa. Fucoxanthin (Fx) is a characteristic orange carotenoid obtained from brown algae and has diverse immunological properties. The present study investigated whether Fx inhibits fibrosis-related effects in nasal polyp-derived fibroblasts (NPDFs) and elucidated the molecular signaling pathways involved. The production of collagen type I (Col-1) was investigated in NP tissue via immunohistochemistry and western blot analysis. NPDFs were treated with transforming growth factor (TGF)-β1 (1 ng/mL) in the presence or absence of Fx (5–30 µM). The levels of α-smooth muscle actin (α-SMA), Col-1, and phosphorylated (p)-Smad 2/3, signal protein-1 (SP-1), MAPKs (mitogen-activated protein kinases), and Akt were measured by western blot analysis. The expression of Col-1 was detected in NP tissues. TGF-β1 stimulated the production of α-SMA and Col-1, and stimulated the contraction of collagen gel. However, pretreatment with Fx attenuated these effects. Furthermore, these inhibitory effects were mediated through modulation of both Smad 2/3 and Akt/SP-1 signaling pathways in TGF-β1-induced NPDFs. The results from the present study suggest that Fx may be a novel anti-fibrotic agent for the treatment of NP formation. Full article
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Open AccessArticle Biogenic Polyphosphate Nanoparticles from a Marine Cyanobacterium Synechococcus sp. PCC 7002: Production, Characterization, and Anti-Inflammatory Properties In Vitro
Mar. Drugs 2018, 16(9), 322; https://doi.org/10.3390/md16090322
Received: 23 August 2018 / Revised: 5 September 2018 / Accepted: 5 September 2018 / Published: 10 September 2018
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Abstract
Probiotic-derived polyphosphates have attracted interest as potential therapeutic agents to improve intestinal health. The current study discovered the intracellular accumulation of polyphosphates in a marine cyanobacterium Synechococcus sp. PCC 7002 as nano-sized granules. The maximum accumulation of polyphosphates in Synechococcus sp. PCC 7002
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Probiotic-derived polyphosphates have attracted interest as potential therapeutic agents to improve intestinal health. The current study discovered the intracellular accumulation of polyphosphates in a marine cyanobacterium Synechococcus sp. PCC 7002 as nano-sized granules. The maximum accumulation of polyphosphates in Synechococcus sp. PCC 7002 was found at the late logarithmic growth phase when the medium contained 0.74 mM of KH2PO4, 11.76 mM of NaNO3, and 30.42 mM of Na2SO4. Biogenic polyphosphate nanoparticles (BPNPs) were obtained intact from the algae cells by hot water extraction, and were purified to remove the organic impurities by Sephadex G-100 gel filtration. By using 100 kDa ultrafiltration, BPNPs were fractionated into the larger and smaller populations with diameters ranging between 30–70 nm and 10–30 nm, respectively. 4′,6-diamidino-2-phenylindole fluorescence and orthophosphate production revealed that a minor portion of BPNPs (about 14–18%) were degraded during simulated gastrointestinal digestion. In vitro studies using lipopolysaccharide-activated RAW264.7 cells showed that BPNPs inhibited cyclooxygenase-2, inducible nitric oxide (NO) synthase expression, and the production of proinflammatory mediators, including NO, tumor necrosis factor-α, interleukin-6, and interleukin-1β through suppressing the Toll-like receptor 4/NF-κB signaling pathway. Overall, there is promise in the use of the marine cyanobacterium Synechococcus sp. PCC 7002 to produce BPNPs, an anti-inflammatory postbiotic. Full article
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Open AccessArticle Fucoidan Extracted from Undaria pinnatifida: Source for Nutraceuticals/Functional Foods
Mar. Drugs 2018, 16(9), 321; https://doi.org/10.3390/md16090321
Received: 31 July 2018 / Revised: 4 September 2018 / Accepted: 8 September 2018 / Published: 9 September 2018
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Abstract
The importance of fucoidan as a functional ingredient in food, health products, and pharmaceutics is well-recognized due to its beneficial biological effects. Fucoidan is usually extracted from brown seaweeds, including Undaria pinnatifida. Fucoidan exhibits beneficial bio-activity and has antioxidant, anticancer, and anticoagulant
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The importance of fucoidan as a functional ingredient in food, health products, and pharmaceutics is well-recognized due to its beneficial biological effects. Fucoidan is usually extracted from brown seaweeds, including Undaria pinnatifida. Fucoidan exhibits beneficial bio-activity and has antioxidant, anticancer, and anticoagulant properties. This review focuses on the biological activity of U. pinnatifida-derived fucoidan and investigates its structure–activity or fraction–activity relationship. It also describes several fucoidan extracts, along with their claimed anticancer effects. It aims to provide information and thoughts for future research such as the development of fucoidan into functional foods or nutraceuticals. Full article
(This article belongs to the Special Issue Pre-Clinical Marine Drug Discovery)
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Open AccessReview Terpenoids from Marine Soft Coral of the Genus Lemnalia: Chemistry and Biological Activities
Mar. Drugs 2018, 16(9), 320; https://doi.org/10.3390/md16090320
Received: 2 August 2018 / Revised: 2 September 2018 / Accepted: 4 September 2018 / Published: 9 September 2018
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Abstract
Lemnalia is one of the most widely-distributed marine soft coral in tropical oceans and is known to produce novel terpenoids with a broad spectrum of biological activities. This review provides the first comprehensive overview of terpenoids produced by soft coral Lemnalia since their
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Lemnalia is one of the most widely-distributed marine soft coral in tropical oceans and is known to produce novel terpenoids with a broad spectrum of biological activities. This review provides the first comprehensive overview of terpenoids produced by soft coral Lemnalia since their first discovery in 1974. Full article
(This article belongs to the Special Issue Terpenoids from Marine Organisms)
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Open AccessReview Lead Compounds from Mangrove-Associated Microorganisms
Mar. Drugs 2018, 16(9), 319; https://doi.org/10.3390/md16090319
Received: 7 August 2018 / Revised: 22 August 2018 / Accepted: 29 August 2018 / Published: 7 September 2018
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Abstract
The mangrove ecosystem is considered as an attractive biodiversity hotspot that is intensively studied in the hope of discovering new useful chemical scaffolds, including those with potential medicinal application. In the past two decades, mangrove-derived microorganisms, along with mangrove plants, proved to be
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The mangrove ecosystem is considered as an attractive biodiversity hotspot that is intensively studied in the hope of discovering new useful chemical scaffolds, including those with potential medicinal application. In the past two decades, mangrove-derived microorganisms, along with mangrove plants, proved to be rich sources of bioactive secondary metabolites as exemplified by the constant rise in the number of publications, which suggests the great potential of this important ecological niche. The present review summarizes selected examples of bioactive compounds either from mangrove endophytes or from soil-derived mangrove fungi and bacteria, covering the literature from 2014 to March 2018. Accordingly, 163 natural products are described in this review, possessing a wide range of potent bioactivities, such as cytotoxic, antibacterial, antifungal, α-glucosidase inhibitory, protein tyrosine phosphatase B inhibitory, and antiviral activities, among others. Full article
(This article belongs to the Special Issue Bioactive Compounds from Mangroves and Their-Associated Microbes)
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Open AccessArticle The Bisindole Alkaloid Caulerpin, from Seaweeds of the Genus Caulerpa, Attenuated Colon Damage in Murine Colitis Model
Mar. Drugs 2018, 16(9), 318; https://doi.org/10.3390/md16090318
Received: 21 July 2018 / Revised: 27 August 2018 / Accepted: 27 August 2018 / Published: 7 September 2018
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Abstract
Caulerpin (CLP), an alkaloid from algae of the genus Caulerpa, has shown anti-inflammatory activity. Therefore, this study aimed to analyze the effect of CLP in the murine model of peritonitis and ulcerative colitis. Firstly, the mice were submitted to peritonitis to evaluate which
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Caulerpin (CLP), an alkaloid from algae of the genus Caulerpa, has shown anti-inflammatory activity. Therefore, this study aimed to analyze the effect of CLP in the murine model of peritonitis and ulcerative colitis. Firstly, the mice were submitted to peritonitis to evaluate which dose of CLP (40, 4, or 0.4 mg/kg) could decrease the inflammatory infiltration in the peritoneum. The most effective doses were 40 and 4 mg/kg. Then, C57BL/6 mice were submitted to colitis development with 3% dextran sulfate sodium (DSS) and treated with CLP at doses of 40 and 4 mg/kg. The disease development was analyzed through the disease activity index (DAI); furthermore, colonic tissue samples were submitted to histological analysis, NFκB determination, and in vitro culture for cytokines assay. Therefore, CLP at 4 mg/kg presented the best results, triggering improvement of DAI and attenuating the colon shortening and damage. This dose was able to reduce the TNF-α, IFN-γ, IL-6, IL-17, and NFκB p65 levels, and increased the levels of IL-10 in the colon tissue. Thus, CLP mice treatment at a dose of 4 mg/kg showed promising results in ameliorating the damage observed in the ulcerative colitis. Full article
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Open AccessArticle Marine Microalgae: Promising Source for New Bioactive Compounds
Mar. Drugs 2018, 16(9), 317; https://doi.org/10.3390/md16090317
Received: 1 August 2018 / Revised: 23 August 2018 / Accepted: 4 September 2018 / Published: 6 September 2018
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Abstract
The study of marine natural products for their bioactive potential has gained strength in recent years. Oceans harbor a vast variety of organisms that offer a biological and chemical diversity with metabolic abilities unrivalled in terrestrial systems, which makes them an attractive target
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The study of marine natural products for their bioactive potential has gained strength in recent years. Oceans harbor a vast variety of organisms that offer a biological and chemical diversity with metabolic abilities unrivalled in terrestrial systems, which makes them an attractive target for bioprospecting as an almost untapped resource of biotechnological applications. Among them, there is no doubt that microalgae could become genuine “cell factories” for the biological synthesis of bioactive substances. Thus, in the course of inter-laboratory collaboration sponsored by the European Union (7th FP) into the MAREX Project focused on the discovery of novel bioactive compounds of marine origin for the European industry, a bioprospecting study on 33 microalgae strains was carried out. The strains were cultured at laboratory scale. Two extracts were prepared for each one (biomass and cell free culture medium) and, thus, screened to provide information on the antimicrobial, the anti-proliferative, and the apoptotic potential of the studied extracts. The outcome of this study provides additional scientific data for the selection of Alexandrium tamarensis WE, Gambierdiscus australes, Prorocentrum arenarium, Prorocentrum hoffmannianum, and Prorocentrum reticulatum (Pr-3) for further investigation and offers support for the continued research of new potential drugs for human therapeutics from cultured microalgae. Full article
(This article belongs to the Special Issue Marine Bioactive Natural Product Studies in Europe)
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Open AccessArticle (+)-Aeroplysinin-1 Modulates the Redox Balance of Endothelial Cells
Mar. Drugs 2018, 16(9), 316; https://doi.org/10.3390/md16090316
Received: 22 July 2018 / Revised: 3 September 2018 / Accepted: 4 September 2018 / Published: 6 September 2018
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Abstract
The bioactive natural compound from marine origin, (+)-aeroplysinin-1, has been shown to exhibit potent anti-inflammatory and anti-angiogenic effects. The aim of the present study was to identify new targets for (+)-aeroplysinin-1 in endothelial cells. The sequential use of 2D-electrophoresis and MALDI-TOF-TOF/MS allowed
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The bioactive natural compound from marine origin, (+)-aeroplysinin-1, has been shown to exhibit potent anti-inflammatory and anti-angiogenic effects. The aim of the present study was to identify new targets for (+)-aeroplysinin-1 in endothelial cells. The sequential use of 2D-electrophoresis and MALDI-TOF-TOF/MS allowed us to identify several differentially expressed proteins. Four of these proteins were involved in redox processes and were validated by Western blot. The effects of (+)-aeroplysinin-1 were further studied by testing the effects of the treatment with this compound on the activity of several anti- and pro-oxidant enzymes, as well as on transcription factors involved in redox homeostasis. Finally, changes in the levels of total reactive oxygen species and mitochondrial membrane potential induced by endothelial cell treatments with (+)-aeroplysinin-1 were also determined. Taken altogether, these findings show that (+)-aeroplysinin-1 has multiple targets involved in endothelial cell redox regulation. Full article
(This article belongs to the Special Issue Halogenated Metabolites)
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Open AccessArticle Synthesis, Characterization, and Antifungal Property of Hydroxypropyltrimethyl Ammonium Chitosan Halogenated Acetates
Mar. Drugs 2018, 16(9), 315; https://doi.org/10.3390/md16090315
Received: 23 July 2018 / Revised: 24 August 2018 / Accepted: 31 August 2018 / Published: 5 September 2018
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Abstract
Hydroxypropyltrimethyl ammonium chitosan halogenated acetates were successfully synthesized from six different haloacetic acids and hydroxypropyltrimethyl ammonium chloride chitosan (HACC) with high substitution degree, which are hydroxypropyltrimethyl ammonium chitosan bromacetate (HACBA), hydroxypropyltrimethyl ammonium chitosan chloroacetate (HACCA), hydroxypropyltrimethyl ammonium chitosan dichloroacetate (HACDCA), hydroxypropyltrimethyl ammonium chitosan
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Hydroxypropyltrimethyl ammonium chitosan halogenated acetates were successfully synthesized from six different haloacetic acids and hydroxypropyltrimethyl ammonium chloride chitosan (HACC) with high substitution degree, which are hydroxypropyltrimethyl ammonium chitosan bromacetate (HACBA), hydroxypropyltrimethyl ammonium chitosan chloroacetate (HACCA), hydroxypropyltrimethyl ammonium chitosan dichloroacetate (HACDCA), hydroxypropyltrimethyl ammonium chitosan trichloroacetate (HACTCA), hydroxypropyltrimethyl ammonium chitosan difluoroacetate (HACDFA), and hydroxypropyltrimethyl ammonium chitosan trifluoroacetate (HACTFA). These chitosan derivatives were synthesized by two steps: first, the hydroxypropyltrimethyl ammonium chloride chitosan was synthesized by chitosan and 3-chloro-2-hydroxypropyltrimethyl ammonium chloride. Then, hydroxypropyltrimethyl ammonium chitosan halogenated acetates were synthesized via ion exchange. The structures of chitosan derivatives were characterized by Fourier transform infrared spectroscopy (FTIR), 1H Nuclear magnetic resonance spectrometer (1H NMR), 13C Nuclear magnetic resonance spectrometer (13C NMR), and elemental analysis. Their antifungal activities against Colletotrichum lagenarium, Fusarium graminearum, Botrytis cinerea, and Phomopsis asparagi were investigated by hypha measurement in vitro. The results revealed that hydroxypropyltrimethyl ammonium chitosan halogenated acetates had better antifungal activities than chitosan and HACC. In particular, the inhibitory activity decreased in the order: HACTFA > HACDFA > HACTCA > HACDCA > HACCA > HACBA > HACC > chitosan, which was consistent with the electron-withdrawing property of different halogenated acetates. This experiment provides a potential idea for the preparation of new antifungal drugs by chitosan. Full article
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Open AccessReview Metabolic and Biosynthetic Diversity in Marine Myxobacteria
Mar. Drugs 2018, 16(9), 314; https://doi.org/10.3390/md16090314
Received: 31 July 2018 / Revised: 24 August 2018 / Accepted: 30 August 2018 / Published: 5 September 2018
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Abstract
Prior to 2005, the vast majority of characterized myxobacteria were obtained from terrestrial habitats. Since then, several species of halotolerant and even obligate marine myxobacteria have been described. Chemical analyses of extracts from these organisms have confirmed their ability to produce secondary metabolites
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Prior to 2005, the vast majority of characterized myxobacteria were obtained from terrestrial habitats. Since then, several species of halotolerant and even obligate marine myxobacteria have been described. Chemical analyses of extracts from these organisms have confirmed their ability to produce secondary metabolites with unique chemical scaffolds. Indeed, new genera of marine-derived myxobacteria, particularly Enhygromyxa, have been shown to produce novel chemical scaffolds that differ from those observed in soil myxobacteria. Further studies have shown that marine sponges and terrestrial myxobacteria are capable of producing similar or even identical secondary metabolites, suggesting that myxobacterial symbionts may have been the true producers. Recent in silico analysis of the genome sequences available from six marine myxobacteria disclosed a remarkably versatile biosynthetic potential. With access to ever-advancing tools for small molecule and genetic evaluation, these studies suggest a bright future for expeditions into this yet untapped resource for secondary metabolites. Full article
(This article belongs to the Special Issue Marine Myxobacteria: Sea Secrets from the Slime)
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Open AccessReview Cognitive Impairment in Chronic Obstructive Pulmonary Disease (COPD): Possible Utility of Marine Bioactive Compounds
Mar. Drugs 2018, 16(9), 313; https://doi.org/10.3390/md16090313
Received: 16 July 2018 / Revised: 30 August 2018 / Accepted: 30 August 2018 / Published: 4 September 2018
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Abstract
Chronic obstructive pulmonary disease (COPD) is characterized by long-term airflow limitation. Early-onset COPD in non-smoker subjects is ≥60 years and in the elderly is often associated with different comorbidities. Cognitive impairment is one of the most common feature in patients with COPD, and
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Chronic obstructive pulmonary disease (COPD) is characterized by long-term airflow limitation. Early-onset COPD in non-smoker subjects is ≥60 years and in the elderly is often associated with different comorbidities. Cognitive impairment is one of the most common feature in patients with COPD, and is associated with COPD severity and comorbidities. Cognitive impairment in COPD enhances the assistance requirement in different aspects of daily living, treatment adherence, and effectual self-management.This review describes various bioactive compounds of natural marine sources that modulate different targets shared by both COPD and cognitive impairment and hypothesizes a possible link between these two syndromes. Full article
(This article belongs to the Special Issue Marine Compounds in Neurodegenerative Diseases)
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