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Mar. Drugs, Volume 12, Issue 5 (May 2014), Pages 2341-3090

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Open AccessArticle Omega-3 Polyunsaturated Fatty Acids Protect Neural Progenitor Cells against Oxidative Injury
Mar. Drugs 2014, 12(5), 2341-2356; doi:10.3390/md12052341
Received: 7 February 2014 / Revised: 26 March 2014 / Accepted: 3 April 2014 / Published: 29 April 2014
Cited by 9 | PDF Full-text (1882 KB) | HTML Full-text | XML Full-text
Abstract
The omega-3 polyunsaturated fatty acids (ω-3 PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), derived mainly from fish oil, play important roles in brain development and neuroplasticity. Here, we reported that application of ω-3 PUFAs significantly protected mouse neural progenitor cells (NPCs) [...] Read more.
The omega-3 polyunsaturated fatty acids (ω-3 PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), derived mainly from fish oil, play important roles in brain development and neuroplasticity. Here, we reported that application of ω-3 PUFAs significantly protected mouse neural progenitor cells (NPCs) against H2O2-induced oxidative injury. We also isolated NPCs from transgenic mice expressing the Caenorhabditis elegans fat-1 gene. The fat-1 gene, which is absent in mammals, can add a double bond into an unsaturated fatty acid hydrocarbon chain and convert ω-6 to ω-3 fatty acids. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining showed that a marked decrease in apoptotic cells was found in fat-1 NPCs after oxidative injury with H2O2 as compared with wild-type NPCs. Quantitative RT-PCR and Western blot analysis demonstrated a much higher expression of nuclear factor erythroid 2-related factor 2 (Nrf2), a master transcriptional factor for antioxidant genes, in fat-1 NPCs. The results of the study provide evidence that ω-3 PUFAs resist oxidative injury to NPCs. Full article
Open AccessArticle Extraction of Fucoxanthin from Raw Macroalgae excluding Drying and Cell Wall Disruption by Liquefied Dimethyl Ether
Mar. Drugs 2014, 12(5), 2383-2396; doi:10.3390/md12052383
Received: 19 November 2013 / Revised: 6 January 2014 / Accepted: 26 March 2014 / Published: 30 April 2014
Cited by 4 | PDF Full-text (775 KB) | HTML Full-text | XML Full-text
Abstract
Macroalgae are one of potential sources for carotenoids, such as fucoxanthin, which are consumed by humans and animals. This carotenoid has been applied in both the pharmaceutical and food industries. In this study, extraction of fucoxanthin from wet brown seaweed Undaria pinnatifida [...] Read more.
Macroalgae are one of potential sources for carotenoids, such as fucoxanthin, which are consumed by humans and animals. This carotenoid has been applied in both the pharmaceutical and food industries. In this study, extraction of fucoxanthin from wet brown seaweed Undaria pinnatifida (water content was 93.2%) was carried out with a simple method using liquefied dimethyl ether (DME) as an extractant in semi-continuous flow-type system. The extraction temperature and absolute pressure were 25 °C and 0.59 MPa, respectively. The liquefied DME was passed through the extractor that filled by U. pinnatifida at different time intervals. The time of experiment was only 43 min. The amount of fucoxanthin could approach to 390 μg/g dry of wet U. pinnatifida when the amount of DME used was 286 g. Compared with ethanol Soxhlet and supercritical CO2 extraction, which includes drying and cell disruption, the result was quite high. Thus, DME extraction process appears to be a good method for fucoxanthin recovery from U. pinnatifida with improved yields. Full article
Open AccessArticle Development of Pedigree Classification Using Microsatellite and Mitochondrial Markers for Giant Grouper Broodstock (Epinephelus lanceolatus) Management in Taiwan
Mar. Drugs 2014, 12(5), 2397-2407; doi:10.3390/md12052397
Received: 10 March 2014 / Revised: 3 April 2014 / Accepted: 8 April 2014 / Published: 30 April 2014
Cited by 4 | PDF Full-text (437 KB) | HTML Full-text | XML Full-text
Abstract
Most giant groupers in the market are derived from inbred stock. Inbreeding can cause trait depression, compromising the animals’ fitness and disease resistance, obligating farmers to apply increased amounts of drugs. In order to solve this problem, a pedigree classification method is [...] Read more.
Most giant groupers in the market are derived from inbred stock. Inbreeding can cause trait depression, compromising the animals’ fitness and disease resistance, obligating farmers to apply increased amounts of drugs. In order to solve this problem, a pedigree classification method is needed. Here, microsatellite and mitochondrial DNA were used as genetic markers to analyze the genetic relationships among giant grouper broodstocks. The 776-bp fragment of high polymorphic mitochondrial D-loop sequence was selected for measuring sibling relatedness. In a sample of 118 giant groupers, 42 haplotypes were categorized, with nucleotide diversity (π) of 0.00773 and haplotype diversity (HD) of 0.983. Furthermore, microsatellites were used for investigation of parentage. Six out of 33 microsatellite loci were selected as markers based on having a high number of alleles and compliance with Hardy-Weinberg equilibrium. Microsatellite profiles based on these loci provide high variability with low combined non-exclusion probability, permitting practical use in aquaculture. The method described here could be used to improve grouper broodstock management and lower the chances of inbreeding. This approach is expected to lead to production of higher quality groupers with higher disease resistance, thereby reducing the need for drug application. Full article
Open AccessArticle In Vitro Assessment of Marine Bacillus for Use as Livestock Probiotics
Mar. Drugs 2014, 12(5), 2422-2445; doi:10.3390/md12052422
Received: 25 December 2013 / Revised: 6 February 2014 / Accepted: 1 April 2014 / Published: 30 April 2014
Cited by 3 | PDF Full-text (1072 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Six antimicrobial-producing seaweed-derived Bacillus strains were evaluated in vitro as animal probiotics, in comparison to two Bacillus from an EU-authorized animal probiotic product. Antimicrobial activity was demonstrated on solid media against porcine Salmonella and E. coli. The marine isolates were most active [...] Read more.
Six antimicrobial-producing seaweed-derived Bacillus strains were evaluated in vitro as animal probiotics, in comparison to two Bacillus from an EU-authorized animal probiotic product. Antimicrobial activity was demonstrated on solid media against porcine Salmonella and E. coli. The marine isolates were most active against the latter, had better activity than the commercial probiotics and Bacillus pumilus WIT 588 also reduced E. coli counts in broth. All of the marine Bacillus tolerated physiological concentrations of bile, with some as tolerant as one of the probiotics. Spore counts for all isolates remained almost constant during incubation in simulated gastric and ileum juices. All of the marine Bacillus grew anaerobically and the spores of all except one isolate germinated under anaerobic conditions. All were sensitive to a panel of antibiotics and none harbored Bacillus enterotoxin genes but all, except B. pumilus WIT 588, showed some degree of β-hemolysis. However, trypan blue dye exclusion and xCELLigence assays demonstrated a lack of toxicity in comparison to two pathogens; in fact, the commercial probiotics appeared more cytotoxic than the majority of the marine Bacillus. Overall, some of the marine-derived Bacillus, in particular B. pumilus WIT 588, demonstrate potential for use as livestock probiotics. Full article
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Open AccessArticle Eunicellin-Based Diterpenoids, Hirsutalins N–R, from the Formosan Soft Coral Cladiella hirsuta
Mar. Drugs 2014, 12(5), 2446-2457; doi:10.3390/md12052446
Received: 13 February 2014 / Revised: 24 March 2014 / Accepted: 31 March 2014 / Published: 30 April 2014
Cited by 9 | PDF Full-text (777 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
New eunicellin-type hirsutalins N–R (15), along with two known eunicellins, (6 and 7) were isolated from the soft coral Cladiella hirsuta. The structures of the metabolites were determined by extensive spectroscopic analysis. Cytotoxic activity of [...] Read more.
New eunicellin-type hirsutalins N–R (15), along with two known eunicellins, (6 and 7) were isolated from the soft coral Cladiella hirsuta. The structures of the metabolites were determined by extensive spectroscopic analysis. Cytotoxic activity of compounds 17 against the proliferation of a limited panel of cancer cell lines was measured. The in vitro anti-inflammatory activity of compounds 17 was evaluated by measuring their ability in suppressing superoxide anion generation and elastase release in fMLP/CB-induced human neutrophils. Full article
(This article belongs to the collection Bioactive Compounds from Marine Invertebrates)
Open AccessArticle Marinopyrrole Derivatives as Potential Antibiotic Agents against Methicillin-Resistant Staphylococcus aureus (III)
Mar. Drugs 2014, 12(5), 2458-2470; doi:10.3390/md12052458
Received: 10 February 2014 / Revised: 21 March 2014 / Accepted: 24 March 2014 / Published: 30 April 2014
Cited by 6 | PDF Full-text (848 KB) | HTML Full-text | XML Full-text
Abstract
The marine natural product, marinopyrrole A (1), was previously shown to have significant antibiotic activity against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). Although compound (1) exhibits a significant reduction in MRSA activity in the presence of human [...] Read more.
The marine natural product, marinopyrrole A (1), was previously shown to have significant antibiotic activity against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). Although compound (1) exhibits a significant reduction in MRSA activity in the presence of human serum, we have identified key modifications that partially restore activity. We previously reported our discovery of a chloro-derivative of marinopyrrole A (1a) featuring a 2–4 fold improved minimum inhibitory concentration (MIC) against MRSA, significantly less susceptibility to serum inhibition and rapid and concentration-dependent killing of MRSA. Here, we report a novel fluoro-derivative of marinopyrrole A (1e) showing an improved profile of potency, less susceptibility to serum inhibition, as well as rapid and concentration-dependent killing of MRSA. Full article
Open AccessArticle Antiplatelet and Anticoagulant Effects of Diterpenes Isolated from the Marine Alga, Dictyota menstrualis
Mar. Drugs 2014, 12(5), 2471-2484; doi:10.3390/md12052471
Received: 12 December 2013 / Revised: 1 April 2014 / Accepted: 3 April 2014 / Published: 30 April 2014
Cited by 3 | PDF Full-text (622 KB) | HTML Full-text | XML Full-text
Abstract
Cardiovascular diseases represent a major cause of disability and death worldwide. Therapeutics are available, but they often have unsatisfactory results and may produce side effects. Alternative treatments based on the use of natural products have been extensively investigated, because of their low [...] Read more.
Cardiovascular diseases represent a major cause of disability and death worldwide. Therapeutics are available, but they often have unsatisfactory results and may produce side effects. Alternative treatments based on the use of natural products have been extensively investigated, because of their low toxicity and side effects. Marine organisms are prime candidates for such products, as they are sources of numerous and complex substances with ecological and pharmacological effects. In this work, we investigated, through in vitro experiments, the effects of three diterpenes (pachydictyol A, isopachydictyol A and dichotomanol) from the Brazilian marine alga, Dictyota menstrualis, on platelet aggregation and plasma coagulation. Results showed that dichotomanol inhibited ADP- or collagen-induced aggregation of platelet-rich plasma (PRP), but failed to inhibit washed platelets (WP). In contrast, pachydictyol A and isopachydictyol A failed to inhibit the aggregation of PRP, but inhibited WP aggregation induced by collagen or thrombin. These diterpenes also inhibited coagulation analyzed by the prothrombin time and activated partial thromboplastin time and on commercial fibrinogen. Moreover, diterpenes inhibited the catalytic activity of thrombin. Theoretical studies using the Osiris Property Explorer software showed that diterpenes have low theoretical toxicity profiles and a drug-score similar to commercial anticoagulant drugs. In conclusion, these diterpenes are promising candidates for use in anticoagulant therapy, and this study also highlights the biotechnological potential of oceans and the importance of bioprospecting to develop medicines. Full article
Open AccessArticle Four New Jacaranone Analogs from the Fruits of a Beibu Gulf Mangrove Avicennia marina
Mar. Drugs 2014, 12(5), 2515-2525; doi:10.3390/md12052515
Received: 31 December 2013 / Revised: 10 April 2014 / Accepted: 16 April 2014 / Published: 30 April 2014
Cited by 6 | PDF Full-text (591 KB) | HTML Full-text | XML Full-text
Abstract
Four new jacaranone analogs, marinoids F–I (14), were isolated from the fruits of a Beibu Gulf mangrove Avicennia marina. The structures were elucidated based on analysis of spectroscopic data. Marinoids F and G are shown to be [...] Read more.
Four new jacaranone analogs, marinoids F–I (14), were isolated from the fruits of a Beibu Gulf mangrove Avicennia marina. The structures were elucidated based on analysis of spectroscopic data. Marinoids F and G are shown to be diastereoisomers of chlorocornoside, a new halogen containing marine secondary metabolite. The antioxidant activity of the isolates was evaluated using a cellular antioxidant assay, and 4 showed good antioxidant activity (EC50 = 26 μM). Full article
Open AccessArticle New Benzoxazine Secondary Metabolites from an Arctic Actinomycete
Mar. Drugs 2014, 12(5), 2526-2538; doi:10.3390/md12052526
Received: 12 March 2014 / Revised: 2 April 2014 / Accepted: 15 April 2014 / Published: 30 April 2014
Cited by 7 | PDF Full-text (813 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two new secondary metabolites, arcticoside (1) and C-1027 chromophore-V (2), were isolated along with C-1027 chromophore-III and fijiolides A and B (35) from a culture of an Arctic marine actinomycete Streptomyces strain. The chemical [...] Read more.
Two new secondary metabolites, arcticoside (1) and C-1027 chromophore-V (2), were isolated along with C-1027 chromophore-III and fijiolides A and B (35) from a culture of an Arctic marine actinomycete Streptomyces strain. The chemical structures of 1 and 2 were elucidated through NMR, mass, UV, and IR spectroscopy. The hexose moieties in 1 were determined to be d-glucose from a combination of acid hydrolysis, derivatization, and gas chromatographic analyses. Arcticoside (1) and C-1027 chromophore-V (2), which have a benzoxazine ring, inhibited Candida albicans isocitrate lyase. Chromophore-V (2) exhibited significant cytotoxicity against breast carcinoma MDA-MB231 cells and colorectal carcinoma cells (line HCT-116), with IC50 values of 0.9 and 2.7 μM, respectively. Full article
Open AccessCommunication Identification of Plakortide E from the Caribbean Sponge Plakortis halichondroides as a Trypanocidal Protease Inhibitor using Bioactivity-Guided Fractionation
Mar. Drugs 2014, 12(5), 2614-2622; doi:10.3390/md12052614
Received: 20 February 2014 / Revised: 7 March 2014 / Accepted: 19 March 2014 / Published: 2 May 2014
Cited by 4 | PDF Full-text (215 KB) | HTML Full-text | XML Full-text
Abstract
In this paper, we report new protease inhibitory activity of plakortide E towards cathepsins and cathepsin-like parasitic proteases. We further report on its anti-parasitic activity against Trypanosoma brucei with an IC50 value of 5 μM and without cytotoxic effects against J774.1 [...] Read more.
In this paper, we report new protease inhibitory activity of plakortide E towards cathepsins and cathepsin-like parasitic proteases. We further report on its anti-parasitic activity against Trypanosoma brucei with an IC50 value of 5 μM and without cytotoxic effects against J774.1 macrophages at 100 μM concentration. Plakortide E was isolated from the sponge Plakortis halichondroides using enzyme assay-guided fractionation and identified by NMR spectroscopy and mass spectrometry. Furthermore, enzyme kinetic studies confirmed plakortide E as a non-competitive, slowly-binding, reversible inhibitor of rhodesain. Full article
Open AccessArticle Synthesis of (3S,3′S)- and meso-Stereoisomers of Alloxanthin and Determination of Absolute Configuration of Alloxanthin Isolated from Aquatic Animals
Mar. Drugs 2014, 12(5), 2623-2632; doi:10.3390/md12052623
Received: 20 March 2014 / Revised: 15 April 2014 / Accepted: 15 April 2014 / Published: 8 May 2014
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Abstract
In order to determine the absolute configuration of naturally occurring alloxanthin, a HPLC analytical method for three stereoisomers 1ac was established by using a chiral column. Two authentic samples, (3S,3′S)- and meso-stereoisomers 1b and 1c [...] Read more.
In order to determine the absolute configuration of naturally occurring alloxanthin, a HPLC analytical method for three stereoisomers 1ac was established by using a chiral column. Two authentic samples, (3S,3′S)- and meso-stereoisomers 1b and 1c, were chemically synthesized according to the method previously developed for (3R,3′R)-alloxanthin (1a). Application of this method to various alloxanthin specimens of aquatic animals demonstrated that those isolated from shellfishes, tunicates, and crucian carp are identical with (3R,3′R)-stereoisomer 1a, and unexpectedly those from lake shrimp, catfish, biwa goby, and biwa trout are mixtures of three stereoisomers of 1ac. Full article
(This article belongs to the Special Issue Marine Carotenoids (Special Issue))
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Open AccessArticle Discovery of Novel Saponins from the Viscera of the Sea Cucumber Holothuria lessoni
Mar. Drugs 2014, 12(5), 2633-2667; doi:10.3390/md12052633
Received: 8 February 2014 / Revised: 11 April 2014 / Accepted: 15 April 2014 / Published: 9 May 2014
Cited by 6 | PDF Full-text (627 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Sea cucumbers, sometimes referred to as marine ginseng, produce numerous compounds with diverse functions and are potential sources of active ingredients for agricultural, nutraceutical, pharmaceutical and cosmeceutical products. We examined the viscera of an Australian sea cucumber Holothuria lessoni Massin et al. [...] Read more.
Sea cucumbers, sometimes referred to as marine ginseng, produce numerous compounds with diverse functions and are potential sources of active ingredients for agricultural, nutraceutical, pharmaceutical and cosmeceutical products. We examined the viscera of an Australian sea cucumber Holothuria lessoni Massin et al. 2009, for novel bioactive compounds, with an emphasis on the triterpene glycosides, saponins. The viscera were extracted with 70% ethanol, and this extract was purified by a liquid-liquid partition process and column chromatography, followed by isobutanol extraction. The isobutanol saponin-enriched mixture was further purified by high performance centrifugal partition chromatography (HPCPC) with high purity and recovery. The resultant purified polar samples were analyzed using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS)/MS and electrospray ionization mass spectrometry (ESI-MS)/MS to identify saponins and characterize their molecular structures. As a result, at least 39 new saponins were identified in the viscera of H. lessoni with a high structural diversity, and another 36 reported triterpene glycosides, containing different aglycones and sugar moieties. Viscera samples have provided a higher diversity and yield of compounds than observed from the body wall. The high structural diversity and novelty of saponins from H. lessoni with potential functional activities presents a great opportunity to exploit their applications for industrial, agricultural and pharmaceutical use. Full article
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Open AccessArticle Overexpression and Characterization of a Novel Thermostable β-Agarase YM01-3, from Marine Bacterium Catenovulum agarivorans YM01T
Mar. Drugs 2014, 12(5), 2731-2747; doi:10.3390/md12052731
Received: 26 November 2013 / Revised: 21 April 2014 / Accepted: 22 April 2014 / Published: 12 May 2014
Cited by 5 | PDF Full-text (1335 KB) | HTML Full-text | XML Full-text
Abstract
Genome sequencing of Catenovulum agarivorans YM01T reveals 15 open-reading frames (ORFs) encoding various agarases. In this study, extracellular proteins of YM01T were precipitated by ammonium sulfate and separated by one-dimensional gel electrophoresis. The results of in-gel agarase activity assay and [...] Read more.
Genome sequencing of Catenovulum agarivorans YM01T reveals 15 open-reading frames (ORFs) encoding various agarases. In this study, extracellular proteins of YM01T were precipitated by ammonium sulfate and separated by one-dimensional gel electrophoresis. The results of in-gel agarase activity assay and mass spectrometry analysis revealed that the protein, YM01-3, was an agarase with the most evident agarolytic activity. Agarase YM01-3, encoded by the YM01-3 gene, consisted of 420 amino acids with a calculated molecular mass of 46.9 kDa and contained a glycoside hydrolase family 16 β-agarase module followed by a RICIN superfamily in the C-terminal region. The YM01-3 gene was cloned and expressed in Escherichia coli. The recombinant agarase, YM01-3, showed optimum activity at pH 6.0 and 60 °C and had a Km of 3.78 mg mL−1 for agarose and a Vmax of 1.14 × 104 U mg−1. YM01-3 hydrolyzed the β-1,4-glycosidic linkages of agarose, yielding neoagarotetraose and neoagarohexaose as the main products. Notably, YM01-3 was stable below 50 °C and retained 13% activity after incubation at 80 °C for 1 h, characteristics much different from other agarases. The present study highlights a thermostable agarase with great potential application value in industrial production. Full article
Open AccessCommunication A New Lyngbyatoxin from the Hawaiian Cyanobacterium Moorea producens
Mar. Drugs 2014, 12(5), 2748-2759; doi:10.3390/md12052748
Received: 17 February 2014 / Revised: 6 April 2014 / Accepted: 8 April 2014 / Published: 12 May 2014
Cited by 7 | PDF Full-text (614 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Lyngbyatoxin A from the marine cyanobacterium Moorea producens (formerly Lyngbya majuscula) is known as the causative agent of “swimmer’s itch” with its highly inflammatory effect. A new toxic compound was isolated along with lyngbyatoxin A from an ethyl acetate extract of [...] Read more.
Lyngbyatoxin A from the marine cyanobacterium Moorea producens (formerly Lyngbya majuscula) is known as the causative agent of “swimmer’s itch” with its highly inflammatory effect. A new toxic compound was isolated along with lyngbyatoxin A from an ethyl acetate extract of M. producens collected from Hawaii. Analyses of HR-ESI-MS and NMR spectroscopies revealed the isolated compound had the same planar structure with that of lyngbyatoxin A. The results of optical rotation and CD spectra indicated that the compound was a new lyngbyatoxin A derivative, 12-epi-lyngbyatoxin A (1). While 12-epi-lyngbyatoxin A showed comparable toxicities with lyngbyatoxin A in cytotoxicity and crustacean lethality tests, it showed more than 100 times lower affinity for protein kinase Cδ (PKCδ) using the PKCδ-C1B peptide when compared to lyngbyatoxin A. Full article
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Open AccessArticle New Cyclic Cystine Bridged Peptides from the Sponge Suberites waedoensis
Mar. Drugs 2014, 12(5), 2760-2770; doi:10.3390/md12052760
Received: 11 February 2014 / Revised: 26 March 2014 / Accepted: 21 April 2014 / Published: 12 May 2014
Cited by 2 | PDF Full-text (730 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two new peptides, chujamides A (1) and B (2), were isolated from the marine sponge Suberites waedoensis, which was collected from Korean waters. Based upon the results of the combined spectroscopic analyses, the structures of these compounds [...] Read more.
Two new peptides, chujamides A (1) and B (2), were isolated from the marine sponge Suberites waedoensis, which was collected from Korean waters. Based upon the results of the combined spectroscopic analyses, the structures of these compounds were determined to be proline-riched and cyclic cystine bridged dodeca- and undecapeptides. The absolute configurations of all amino acid residues were determined to be l by advanced Marfey’s analysis. The new compounds exhibited weak cytotoxicities against A549 and K562 cell-lines, and compound 2 also demonstrated moderate inhibitory activity against Na+/K+-ATPase. Full article
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Open AccessArticle Actinomycetes from Red Sea Sponges: Sources for Chemical and Phylogenetic Diversity
Mar. Drugs 2014, 12(5), 2771-2789; doi:10.3390/md12052771
Received: 25 March 2014 / Revised: 10 April 2014 / Accepted: 14 April 2014 / Published: 12 May 2014
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Abstract
The diversity of actinomycetes associated with marine sponges collected off Fsar Reef (Saudi Arabia) was investigated in the present study. Forty-seven actinomycetes were cultivated and phylogenetically identified based on 16S rRNA gene sequencing and were assigned to 10 different actinomycete genera. Eight [...] Read more.
The diversity of actinomycetes associated with marine sponges collected off Fsar Reef (Saudi Arabia) was investigated in the present study. Forty-seven actinomycetes were cultivated and phylogenetically identified based on 16S rRNA gene sequencing and were assigned to 10 different actinomycete genera. Eight putatively novel species belonging to genera Kocuria, Mycobacterium, Nocardia, and Rhodococcus were identified based on sequence similarity values below 98.2% to other 16S rRNA gene sequences available in the NCBI database. PCR-based screening for biosynthetic genes including type I and type II polyketide synthases (PKS-I, PKS-II) as well as nonribosomal peptide synthetases (NRPS) showed that 20 actinomycete isolates encoded each at least one type of biosynthetic gene. The organic extracts of nine isolates displayed bioactivity against at least one of the test pathogens, which were Gram-positive and Gram-negative bacteria, fungi, human parasites, as well as in a West Nile Virus protease enzymatic assay. These results emphasize that marine sponges are a prolific resource for novel bioactive actinomycetes with potential for drug discovery. Full article
Open AccessArticle Marine Compound Catunaregin Inhibits Angiogenesis through the Modulation of Phosphorylation of Akt and eNOS in vivo and in vitro
Mar. Drugs 2014, 12(5), 2790-2801; doi:10.3390/md12052790
Received: 10 February 2014 / Revised: 9 April 2014 / Accepted: 14 April 2014 / Published: 12 May 2014
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Abstract
Angiogenesis is the formation of blood vessels from pre-existing vasculature. Excessive or uncontrolled angiogenesis is a major contributor to many pathological conditions whereas inhibition of aberrant angiogenesis is beneficial to patients with pathological angiogenesis. Catunaregin is a core of novel marine compound [...] Read more.
Angiogenesis is the formation of blood vessels from pre-existing vasculature. Excessive or uncontrolled angiogenesis is a major contributor to many pathological conditions whereas inhibition of aberrant angiogenesis is beneficial to patients with pathological angiogenesis. Catunaregin is a core of novel marine compound isolated from mangrove associate. The potential anti-angiogenesis of catunaregin was investigated in human umbilical vein endothelial cells (HUVECs) and zebrafish. HUVECs were treated with different concentrations of catunaregin in the presence or absence of VEGF. The angiogenic phenotypes including cell invasion cell migration and tube formation were evaluated following catunaregin treatment in HUVECs. The possible involvement of AKT, eNOS and ERK1/2 in catunaregin-induced anti-angiogenesis was explored using Western blotting. The anti-angiogenesis of catunaregin was further tested in the zebrafish embryo neovascularization and caudal fin regeneration assays. We found that catunaregin dose-dependently inhibited angiogenesis in both HUVECs and zebrafish embryo neovascularization and zebrafish caudal fin regeneration assays. In addition, catunaregin significantly decreased the phosphorylation of Akt and eNOS, but not the phosphorylation of ERK1/2. The present work demonstrates that catunaregin exerts the anti-angiogenic activity at least in part through the regulation of the Akt and eNOS signaling pathways. Full article
Open AccessArticle A Coralline Algal-Associated Bacterium, Pseudoalteromonas Strain J010, Yields Five New Korormicins and a Bromopyrrole
Mar. Drugs 2014, 12(5), 2802-2815; doi:10.3390/md12052802
Received: 7 February 2014 / Revised: 23 April 2014 / Accepted: 24 April 2014 / Published: 13 May 2014
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Abstract
The ethanol extract of Pseudoalteromonas strain J010, isolated from the surface of the crustose coralline alga Neogoniolithon fosliei, yielded thirteen natural products. These included a new bromopyrrole, 4′-((3,4,5-tribromo-1H-pyrrol-2-yl) methyl)phenol (1) and five new korormicins G–K (2 [...] Read more.
The ethanol extract of Pseudoalteromonas strain J010, isolated from the surface of the crustose coralline alga Neogoniolithon fosliei, yielded thirteen natural products. These included a new bromopyrrole, 4′-((3,4,5-tribromo-1H-pyrrol-2-yl) methyl)phenol (1) and five new korormicins G–K (26). Also isolated was the known inducer of coral larval metamorphosis, tetrabromopyrrole (TBP), five known korormicins (A–E, previously named 1, 1a–c and 3) and bromoalterochromide A (BAC-A). Structures of the new compounds were elucidated through interpretation of spectra obtained after extensive NMR and MS investigations and comparison with literature values. The antibacterial, antifungal and antiprotozoal potential of 16, TBP and BAC-A was assessed. Compounds 16 showed antibacterial activity while BAC-A exhibited antiprotozoal properties against Tetrahymena pyriformis. TBP was found to have broad-spectrum activity against all bacteria, the protozoan and the fungus Candida albicans. Full article
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Open AccessArticle Cyclodepsipeptides and Other O-Containing Heterocyclic Metabolites from Beauveria felina EN-135, a Marine-Derived Entomopathogenic Fungus
Mar. Drugs 2014, 12(5), 2816-2826; doi:10.3390/md12052816
Received: 2 February 2014 / Revised: 25 March 2014 / Accepted: 28 April 2014 / Published: 13 May 2014
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Abstract
Bioassay-guided fractionation of a culture extract of Beauveria felina EN-135, an entomopathogenic fungus isolated from a marine bryozoan, led to the isolation of a new cyclodepsipeptide, iso-isariin D (1); two new O-containing heterocyclic compounds that we have named felinones [...] Read more.
Bioassay-guided fractionation of a culture extract of Beauveria felina EN-135, an entomopathogenic fungus isolated from a marine bryozoan, led to the isolation of a new cyclodepsipeptide, iso-isariin D (1); two new O-containing heterocyclic compounds that we have named felinones A and B (2 and 3); and four known cyclodepsipeptides (47). The structures were elucidated via spectroscopic analysis, and the absolute configurations of 1 and 2 were determined using single-crystal X-ray diffraction and CD, respectively. All isolated compounds were evaluated for antimicrobial activity and brine-shrimp (Artemia salina) lethality. Full article
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Open AccessArticle In Situ Detection of Antibiotic Amphotericin B Produced in Streptomyces nodosus Using Raman Microspectroscopy
Mar. Drugs 2014, 12(5), 2827-2839; doi:10.3390/md12052827
Received: 17 March 2014 / Revised: 17 April 2014 / Accepted: 24 April 2014 / Published: 13 May 2014
Cited by 1 | PDF Full-text (939 KB) | HTML Full-text | XML Full-text
Abstract
The study of spatial distribution of secondary metabolites within microbial cells facilitates the screening of candidate strains from marine environments for functional metabolites and allows for the subsequent assessment of the production of metabolites, such as antibiotics. This paper demonstrates the first [...] Read more.
The study of spatial distribution of secondary metabolites within microbial cells facilitates the screening of candidate strains from marine environments for functional metabolites and allows for the subsequent assessment of the production of metabolites, such as antibiotics. This paper demonstrates the first application of Raman microspectroscopy for in situ detection of the antifungal antibiotic amphotericin B (AmB) produced by actinomycetes—Streptomyces nodosus. Raman spectra measured from hyphae of S. nodosus show the specific Raman bands, caused by resonance enhancement, corresponding to the polyene chain of AmB. In addition, Raman microspectroscopy enabled us to monitor the time-dependent change of AmB production corresponding to the growth of mycelia. The Raman images of S. nodosus reveal the heterogeneous distribution of AmB within the mycelia and individual hyphae. Moreover, the molecular association state of AmB in the mycelia was directly identified by observed Raman spectral shifts. These findings suggest that Raman microspectroscopy could be used for in situ monitoring of antibiotic production directly in marine microorganisms with a method that is non-destructive and does not require labeling. Full article
Open AccessArticle Three New Resveratrol Derivatives from the Mangrove Endophytic Fungus Alternaria sp.
Mar. Drugs 2014, 12(5), 2840-2850; doi:10.3390/md12052840
Received: 31 January 2014 / Revised: 2 March 2014 / Accepted: 22 April 2014 / Published: 13 May 2014
Cited by 8 | PDF Full-text (748 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Three new resveratrol derivatives, namely, resveratrodehydes A–C (13), were isolated from the mangrove endophytic fungus Alternaria sp. R6. The structures of these compounds were elucidated by analysis of their MS, 1D and 2D NMR spectroscopic data. All compounds [...] Read more.
Three new resveratrol derivatives, namely, resveratrodehydes A–C (13), were isolated from the mangrove endophytic fungus Alternaria sp. R6. The structures of these compounds were elucidated by analysis of their MS, 1D and 2D NMR spectroscopic data. All compounds showed broad-spectrum inhibitory activities against three human cancer cell lines including human breast MDA-MB-435, human liver HepG2, and human colon HCT-116 by MTT assay (IC50 < 50 μM). Among them, compounds 1 and 2 both exhibited marked cytotoxic activities against MDA-MB-435 and HCT-116 cell lines (IC50 < 10 μM). Additionally, compounds 1 and 3 showed moderate antioxidant activity by DPPH radical scavenging assay. Full article
Open AccessArticle Complex Toxin Profile of French Mediterranean Ostreopsis cf. ovata Strains, Seafood Accumulation and Ovatoxins Prepurification
Mar. Drugs 2014, 12(5), 2851-2876; doi:10.3390/md12052851
Received: 13 March 2014 / Revised: 15 April 2014 / Accepted: 24 April 2014 / Published: 13 May 2014
Cited by 16 | PDF Full-text (894 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Ostreopsis cf. ovata produces palytoxin analogues including ovatoxins (OVTXs) and a putative palytoxin (p-PLTX), which can accumulate in marine organisms and may possibly lead to food intoxication. However, purified ovatoxins are not widely available and their toxicities are still unknown. The aim [...] Read more.
Ostreopsis cf. ovata produces palytoxin analogues including ovatoxins (OVTXs) and a putative palytoxin (p-PLTX), which can accumulate in marine organisms and may possibly lead to food intoxication. However, purified ovatoxins are not widely available and their toxicities are still unknown. The aim of this study was to improve understanding of the ecophysiology of Ostreopsis cf. ovata and its toxin production as well as to optimize the purification process for ovatoxin. During Ostreopsis blooms in 2011 and 2012 in Villefranche-sur-Mer (France, NW Mediterranean Sea), microalgae epiphytic cells and marine organisms were collected and analyzed both by LC-MS/MS and hemolysis assay. Results obtained with these two methods were comparable, suggesting ovatoxins have hemolytic properties. An average of 223 μg·kg−1 of palytoxin equivalent of whole flesh was found, thus exceeding the threshold of 30 μg·kg−1 in shellfish recommended by the European Food Safety Authority (EFSA). Ostreopsis cells showed the same toxin profile both in situ and in laboratory culture, with ovatoxin-a (OVTX-a) being the most abundant analogue (~50%), followed by OVTX-b (~15%), p-PLTX (12%), OVTX-d (8%), OVTX-c (5%) and OVTX-e (4%). Ostreopsis cf. ovata produced up to 2 g of biomass per L of culture, with a maximum concentration of 300 pg PLTX equivalent cell−1. Thus, an approximate amount of 10 mg of PLTX-group toxins may be produced with 10 L of this strain. Toxin extracts obtained from collected biomass were purified using different techniques such as liquid-liquid partition or size exclusion. Among these methods, open-column chromatography with Sephadex LH20 phase yielded the best results with a cleanup efficiency of 93% and recovery of about 85%, representing an increase of toxin percentage by 13 fold. Hence, this purification step should be incorporated into future isolation exercises. Full article
Open AccessArticle Antibacterial and Antiyeast Compounds from Marine-Derived Bacteria
Mar. Drugs 2014, 12(5), 2913-2921; doi:10.3390/md12052913
Received: 25 December 2013 / Revised: 4 March 2014 / Accepted: 18 April 2014 / Published: 13 May 2014
Cited by 3 | PDF Full-text (529 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two new (2 and 3) and a known (1) antimicrobial compounds were isolated from EtOAc extracts of two marine bacterial strains cultured in modified Bennett’s broth medium. The structures of these compounds were determined based on the analysis [...] Read more.
Two new (2 and 3) and a known (1) antimicrobial compounds were isolated from EtOAc extracts of two marine bacterial strains cultured in modified Bennett’s broth medium. The structures of these compounds were determined based on the analysis of nuclear magnetic resonance (NMR), high resolution mass spectroscopy (HRMS), literature data review and considering biogenesis. All the compounds (13) demonstrated in vitro antimicrobial activities against selected pathogenic strains. Full article
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Open AccessArticle Echinochrome A Protects Mitochondrial Function in Cardiomyocytes against Cardiotoxic Drugs
Mar. Drugs 2014, 12(5), 2922-2936; doi:10.3390/md12052922
Received: 27 March 2014 / Revised: 22 April 2014 / Accepted: 28 April 2014 / Published: 13 May 2014
Cited by 9 | PDF Full-text (531 KB) | HTML Full-text | XML Full-text
Abstract
Echinochrome A (Ech A) is a naphthoquinoid pigment from sea urchins that possesses antioxidant, antimicrobial, anti-inflammatory and chelating abilities. Although Ech A is the active substance in the ophthalmic and cardiac drug Histochrome®, its underlying cardioprotective mechanisms are not well [...] Read more.
Echinochrome A (Ech A) is a naphthoquinoid pigment from sea urchins that possesses antioxidant, antimicrobial, anti-inflammatory and chelating abilities. Although Ech A is the active substance in the ophthalmic and cardiac drug Histochrome®, its underlying cardioprotective mechanisms are not well understood. In this study, we investigated the protective role of Ech A against toxic agents that induce death of rat cardiac myoblast H9c2 cells and isolated rat cardiomyocytes. We found that the cardiotoxic agents tert-Butyl hydroperoxide (tBHP, organic reactive oxygen species (ROS) inducer), sodium nitroprusside (SNP; anti-hypertension drug), and doxorubicin (anti-cancer drug) caused mitochondrial dysfunction such as increased ROS level and decreased mitochondrial membrane potential. Co-treatment with Ech A, however, prevented this decrease in membrane potential and increase in ROS level. Co-treatment of Ech A also reduced the effects of these cardiotoxic agents on mitochondrial oxidative phosphorylation and adenosine triphosphate level. These findings indicate the therapeutic potential of Ech A for reducing cardiotoxic agent-induced damage. Full article
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Open AccessCommunication Isolation and Identification of Antitrypanosomal and Antimycobacterial Active Steroids from the Sponge Haliclona simulans
Mar. Drugs 2014, 12(5), 2937-2952; doi:10.3390/md12052937
Received: 30 January 2014 / Revised: 25 April 2014 / Accepted: 28 April 2014 / Published: 16 May 2014
Cited by 6 | PDF Full-text (1163 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The marine sponge Haliclona simulans collected from the Irish Sea yielded two new steroids: 24-vinyl-cholest-9-ene-3β,24-diol and 20-methyl-pregn-6-en-3β-ol,5a,8a-epidioxy, along with the widely distributed 24-methylenecholesterol. One of the steroids possesses an unusually short hydrocarbon side chain. The structures were elucidated using nuclear magnetic resonance [...] Read more.
The marine sponge Haliclona simulans collected from the Irish Sea yielded two new steroids: 24-vinyl-cholest-9-ene-3β,24-diol and 20-methyl-pregn-6-en-3β-ol,5a,8a-epidioxy, along with the widely distributed 24-methylenecholesterol. One of the steroids possesses an unusually short hydrocarbon side chain. The structures were elucidated using nuclear magnetic resonance spectroscopy and confirmed using electron impact- and high resolution electrospray-mass spectrometry. All three steroids possess antitrypanosomal and anti-mycobacterial activity. All the steroids were found to possess low cytotoxicity against Hs27 which was above their detected antitrypanosomal potent concentrations. Full article
(This article belongs to the collection Bioactive Compounds from Marine Invertebrates)
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Open AccessArticle Alterporriol-Type Dimers from the Mangrove Endophytic Fungus, Alternaria sp. (SK11), and Their MptpB Inhibitions
Mar. Drugs 2014, 12(5), 2953-2969; doi:10.3390/md12052953
Received: 20 March 2014 / Revised: 22 April 2014 / Accepted: 25 April 2014 / Published: 16 May 2014
Cited by 6 | PDF Full-text (769 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A new alterporriol-type anthranoid dimer, alterporriol S (1), along with seven known anthraquinone derivatives, (+)-aS-alterporriol C (2), hydroxybostrycin (3), halorosellinia A (4), tetrahydrobostrycin (5), 9α-hydroxydihydrodesoxybostrycin (6), austrocortinin ( [...] Read more.
A new alterporriol-type anthranoid dimer, alterporriol S (1), along with seven known anthraquinone derivatives, (+)-aS-alterporriol C (2), hydroxybostrycin (3), halorosellinia A (4), tetrahydrobostrycin (5), 9α-hydroxydihydrodesoxybostrycin (6), austrocortinin (7) and 6-methylquinizarin (8), were isolated from the culture broth of the mangrove fungus, Alternaria sp. (SK11), from the South China Sea. Their structures and the relative configurations were elucidated using comprehensive spectroscopic methods, including 1D and 2D NMR spectra. The absolute configurations of 1 and the axial configuration of 2 were defined by experimental and theoretical ECD spectroscopy. 1 was identified as the first member of alterporriols consisting of a unique C-10−C-2′ linkage. Atropisomer 2 exhibited strong inhibitory activity against Mycobacterium tuberculosis protein tyrosine phosphatase B (MptpB) with an IC50 value 8.70 μM. Full article
(This article belongs to the Special Issue Bioactive Compounds from Marine Microbes)
Open AccessArticle Production of Induced Secondary Metabolites by a Co-Culture of Sponge-Associated Actinomycetes, Actinokineospora sp. EG49 and Nocardiopsis sp. RV163
Mar. Drugs 2014, 12(5), 3046-3059; doi:10.3390/md12053046
Received: 7 January 2014 / Revised: 4 March 2014 / Accepted: 10 April 2014 / Published: 22 May 2014
Cited by 14 | PDF Full-text (781 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two sponge-derived actinomycetes, Actinokineospora sp. EG49 and Nocardiopsis sp. RV163, were grown in co-culture and the presence of induced metabolites monitored by 1H NMR. Ten known compounds, including angucycline, diketopiperazine and β-carboline derivatives 110, were isolated from the [...] Read more.
Two sponge-derived actinomycetes, Actinokineospora sp. EG49 and Nocardiopsis sp. RV163, were grown in co-culture and the presence of induced metabolites monitored by 1H NMR. Ten known compounds, including angucycline, diketopiperazine and β-carboline derivatives 110, were isolated from the EtOAc extracts of Actinokineospora sp. EG49 and Nocardiopsis sp. RV163. Co-cultivation of Actinokineospora sp. EG49 and Nocardiopsis sp. RV163 induced the biosynthesis of three natural products that were not detected in the single culture of either microorganism, namely N-(2-hydroxyphenyl)-acetamide (11), 1,6-dihydroxyphenazine (12) and 5a,6,11a,12-tetrahydro-5a,11a-dimethyl[1,4]benzoxazino[3,2-b][1,4]benzoxazine (13a). When tested for biological activity against a range of bacteria and parasites, only the phenazine 12 was active against Bacillus sp. P25, Trypanosoma brucei and interestingly, against Actinokineospora sp. EG49. These findings highlight the co-cultivation approach as an effective strategy to access the bioactive secondary metabolites hidden in the genomes of marine actinomycetes. Full article
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Open AccessArticle Klymollins T–X, Bioactive Eunicellin-Based Diterpenoids from the Soft Coral Klyxum molle
Mar. Drugs 2014, 12(5), 3060-3071; doi:10.3390/md12053060
Received: 4 January 2014 / Revised: 18 April 2014 / Accepted: 29 April 2014 / Published: 22 May 2014
Cited by 4 | PDF Full-text (1015 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Five new eunicellin-based diterpenoids, klymollins T–X (15), along with two known compounds (6 and 7) have been isolated from the soft coral Klyxum molle. The structures of these new metabolites were elucidated by extensive spectroscopic [...] Read more.
Five new eunicellin-based diterpenoids, klymollins T–X (15), along with two known compounds (6 and 7) have been isolated from the soft coral Klyxum molle. The structures of these new metabolites were elucidated by extensive spectroscopic analysis and by comparison with related known compounds. Compound 5 was found to exert significant in vitro anti-inflammatory activity against LPS-stimulated RAW264.7 macrophage cells. Furthermore, compounds 4 and 7 were shown to exhibit cytotoxicity against a limited panel of human cancer cell lines. Full article
Open AccessArticle Cracking the Cytotoxicity Code: Apoptotic Induction of 10-Acetylirciformonin B is Mediated through ROS Generation and Mitochondrial Dysfunction
Mar. Drugs 2014, 12(5), 3072-3090; doi:10.3390/md12053072
Received: 21 November 2013 / Revised: 4 April 2014 / Accepted: 16 April 2014 / Published: 22 May 2014
Cited by 6 | PDF Full-text (1292 KB) | HTML Full-text | XML Full-text
Abstract
A marine furanoterpenoid derivative, 10-acetylirciformonin B (10AB), was found to inhibit the proliferation of leukemia, hepatoma, and colon cancer cell lines, with selective and significant potency against leukemia cells. It induced DNA damage and apoptosis in leukemia HL 60 cells. To fully [...] Read more.
A marine furanoterpenoid derivative, 10-acetylirciformonin B (10AB), was found to inhibit the proliferation of leukemia, hepatoma, and colon cancer cell lines, with selective and significant potency against leukemia cells. It induced DNA damage and apoptosis in leukemia HL 60 cells. To fully understand the mechanism behind the 10AB apoptotic induction against HL 60 cells, we extended our previous findings and further explored the precise molecular targets of 10AB. We found that the use of 10AB increased apoptosis by 8.9%–87.6% and caused disruption of mitochondrial membrane potential (MMP) by 15.2%–95.2% in a dose-dependent manner, as demonstrated by annexin-V/PI and JC-1 staining assays, respectively. Moreover, our findings indicated that the pretreatment of HL 60 cells with N-acetyl-l-cysteine (NAC), a reactive oxygen species (ROS) scavenger, diminished MMP disruption and apoptosis induced by 10AB, suggesting that ROS overproduction plays a crucial rule in the cytotoxic activity of 10AB. The results of a cell-free system assay indicated that 10AB could act as a topoisomerase catalytic inhibitor through the inhibition of topoisomerase IIα. On the protein level, the expression of the anti-apoptotic proteins Bcl-xL and Bcl-2, caspase inhibitors XIAP and survivin, as well as hexokinase II were inhibited by the use of 10AB. On the other hand, the expression of the pro-apoptotic protein Bax was increased after 10AB treatment. Taken together, our results suggest that 10AB-induced apoptosis is mediated through the overproduction of ROS and the disruption of mitochondrial metabolism. Full article

Review

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Open AccessReview Marine Bioactives and Potential Application in Sports
Mar. Drugs 2014, 12(5), 2357-2382; doi:10.3390/md12052357
Received: 10 October 2013 / Revised: 24 March 2014 / Accepted: 26 March 2014 / Published: 30 April 2014
Cited by 6 | PDF Full-text (400 KB) | HTML Full-text | XML Full-text
Abstract
An enriched diet with antioxidants, such as vitamin E, vitamin C, β-carotene and phenolic compounds, has always been suggested to improve oxidative stress, preventing related diseases. In this respect, marine natural product (MNP), such as COX inhibitors, marine steroids, molecules interfering with [...] Read more.
An enriched diet with antioxidants, such as vitamin E, vitamin C, β-carotene and phenolic compounds, has always been suggested to improve oxidative stress, preventing related diseases. In this respect, marine natural product (MNP), such as COX inhibitors, marine steroids, molecules interfering with factors involved in the modulation of gene expression (such as NF-κB), macrolides, many antioxidant agents, thermogenic substances and even substances that could help the immune system and that result in the protection of cartilage, have been recently gaining attention. The marine world represents a reserve of bioactive ingredients, with considerable potential as functional food. Substances, such as chitin, chitosan, n-3 oils, carotenoids, vitamins, minerals and bioactive peptides, can provide several health benefits, such as the reduction of cardiovascular diseases, anti-inflammatory and anticarcinogenic activities. In addition, new marine bioactive substances with potential anti-inflammatory, antioxidant and thermogenic capacity may provide health benefits and performance improvement, especially in those who practice physical activity, because of their increased free radical and Reacting Oxygen Species (ROS) production during exercise, and, particularly, in athletes. The aim of this review is to examine the potential pharmacological properties and application of many marine bioactive substances in sports. Full article
Open AccessReview Pathophysiological Effects of Synthetic Derivatives of Polymeric Alkylpyridinium Salts from the Marine Sponge, Reniera sarai
Mar. Drugs 2014, 12(5), 2408-2421; doi:10.3390/md12052408
Received: 17 March 2014 / Revised: 4 April 2014 / Accepted: 4 April 2014 / Published: 30 April 2014
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Abstract
Polymeric 3-alkylpyridinium salts (poly-APS) are among the most studied natural bioactive compounds extracted from the marine sponge, Reniera sarai. They exhibit a wide range of biological activities, and the most prominent among them are the anti-acetylcholinesterase and membrane-damaging activity. Due to [...] Read more.
Polymeric 3-alkylpyridinium salts (poly-APS) are among the most studied natural bioactive compounds extracted from the marine sponge, Reniera sarai. They exhibit a wide range of biological activities, and the most prominent among them are the anti-acetylcholinesterase and membrane-damaging activity. Due to their membrane activity, sAPS can induce the lysis of various cells and cell lines and inhibit the growth of bacteria and fungi. Because of their bioactivity, poly-APS are possible candidates for use in the fields of medicine, pharmacy and industry. Due to the small amounts of naturally occurring poly-APS, methods for the synthesis of analogues have been developed. They differ in chemical properties, such as the degree of polymerization, the length of the alkyl chains (from three to 12 carbon atoms) and in the counter ions present in their structures. Such structurally defined analogues with different chemical properties and degrees of polymerization possess different levels of biological activity. We review the current knowledge of the biological activity and toxicity of synthetic poly-APS analogues, with particular emphasis on the mechanisms of their physiological and pharmacological effects and, in particular, the mechanisms of toxicity of two analogues, APS12-2 and APS3, in vivo and in vitro. Full article
(This article belongs to the collection Bioactive Compounds from Marine Invertebrates)
Open AccessReview Gram-Negative Marine Bacteria: Structural Features of Lipopolysaccharides and Their Relevance for Economically Important Diseases
Mar. Drugs 2014, 12(5), 2485-2514; doi:10.3390/md12052485
Received: 7 December 2013 / Revised: 3 March 2014 / Accepted: 8 April 2014 / Published: 30 April 2014
Cited by 6 | PDF Full-text (1065 KB) | HTML Full-text | XML Full-text
Abstract
Gram-negative marine bacteria can thrive in harsh oceanic conditions, partly because of the structural diversity of the cell wall and its components, particularly lipopolysaccharide (LPS). LPS is composed of three main parts, an O-antigen, lipid A, and a core region, all of [...] Read more.
Gram-negative marine bacteria can thrive in harsh oceanic conditions, partly because of the structural diversity of the cell wall and its components, particularly lipopolysaccharide (LPS). LPS is composed of three main parts, an O-antigen, lipid A, and a core region, all of which display immense structural variations among different bacterial species. These components not only provide cell integrity but also elicit an immune response in the host, which ranges from other marine organisms to humans. Toll-like receptor 4 and its homologs are the dedicated receptors that detect LPS and trigger the immune system to respond, often causing a wide variety of inflammatory diseases and even death. This review describes the structural organization of selected LPSes and their association with economically important diseases in marine organisms. In addition, the potential therapeutic use of LPS as an immune adjuvant in different diseases is highlighted. Full article
(This article belongs to the Special Issue Marine Lipopolysaccharides)
Open AccessReview Bioactive Marine Drugs and Marine Biomaterials for Brain Diseases
Mar. Drugs 2014, 12(5), 2539-2589; doi:10.3390/md12052539
Received: 30 January 2014 / Revised: 10 April 2014 / Accepted: 16 April 2014 / Published: 2 May 2014
Cited by 7 | PDF Full-text (1670 KB) | HTML Full-text | XML Full-text
Abstract
Marine invertebrates produce a plethora of bioactive compounds, which serve as inspiration for marine biotechnology, particularly in drug discovery programs and biomaterials development. This review aims to summarize the potential of drugs derived from marine invertebrates in the field of neuroscience. Therefore, [...] Read more.
Marine invertebrates produce a plethora of bioactive compounds, which serve as inspiration for marine biotechnology, particularly in drug discovery programs and biomaterials development. This review aims to summarize the potential of drugs derived from marine invertebrates in the field of neuroscience. Therefore, some examples of neuroprotective drugs and neurotoxins will be discussed. Their role in neuroscience research and development of new therapies targeting the central nervous system will be addressed, with particular focus on neuroinflammation and neurodegeneration. In addition, the neuronal growth promoted by marine drugs, as well as the recent advances in neural tissue engineering, will be highlighted. Full article
Open AccessReview Natural Products from Mangrove Actinomycetes
Mar. Drugs 2014, 12(5), 2590-2613; doi:10.3390/md12052590
Received: 30 November 2013 / Revised: 31 March 2014 / Accepted: 15 April 2014 / Published: 2 May 2014
Cited by 15 | PDF Full-text (498 KB) | HTML Full-text | XML Full-text
Abstract
Mangroves are woody plants located in tropical and subtropical intertidal coastal regions. The mangrove ecosystem is becoming a hot spot for natural product discovery and bioactivity survey. Diverse mangrove actinomycetes as promising and productive sources are worth being explored and uncovered. At [...] Read more.
Mangroves are woody plants located in tropical and subtropical intertidal coastal regions. The mangrove ecosystem is becoming a hot spot for natural product discovery and bioactivity survey. Diverse mangrove actinomycetes as promising and productive sources are worth being explored and uncovered. At the time of writing, we report 73 novel compounds and 49 known compounds isolated from mangrove actinomycetes including alkaloids, benzene derivatives, cyclopentenone derivatives, dilactones, macrolides, 2-pyranones and sesquiterpenes. Attractive structures such as salinosporamides, xiamycins and novel indolocarbazoles are highlighted. Many exciting compounds have been proven as potential new antibiotics, antitumor and antiviral agents, anti-fibrotic agents and antioxidants. Furthermore, some of their biosynthetic pathways have also been revealed. This review is an attempt to consolidate and summarize the past and the latest studies on mangrove actinomycetes natural product discovery and to draw attention to their immense potential as novel and bioactive compounds for marine drugs discovery. Full article
Open AccessReview Biosynthetic Modularity Rules in the Bisintercalator Family of Antitumor Compounds
Mar. Drugs 2014, 12(5), 2668-2699; doi:10.3390/md12052668
Received: 29 January 2014 / Revised: 9 April 2014 / Accepted: 11 April 2014 / Published: 9 May 2014
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Abstract
Diverse actinomycetes produce a family of structurally and biosynthetically related non-ribosomal peptide compounds which belong to the chromodepsipeptide family. These compounds act as bisintercalators into the DNA helix. They give rise to antitumor, antiparasitic, antibacterial and antiviral bioactivities. These compounds show a [...] Read more.
Diverse actinomycetes produce a family of structurally and biosynthetically related non-ribosomal peptide compounds which belong to the chromodepsipeptide family. These compounds act as bisintercalators into the DNA helix. They give rise to antitumor, antiparasitic, antibacterial and antiviral bioactivities. These compounds show a high degree of conserved modularity (chromophores, number and type of amino acids). This modularity and their high sequence similarities at the genetic level imply a common biosynthetic origin for these pathways. Here, we describe insights about rules governing this modular biosynthesis, taking advantage of the fact that nowadays five of these gene clusters have been made public (thiocoraline, triostin, SW-163 and echinomycin/quinomycin). This modularity has potential application for designing and producing novel genetic engineered derivatives, as well as for developing new chemical synthesis strategies. These would facilitate their clinical development. Full article
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Open AccessReview Cephalopod Ink: Production, Chemistry, Functions and Applications
Mar. Drugs 2014, 12(5), 2700-2730; doi:10.3390/md12052700
Received: 14 March 2014 / Revised: 10 April 2014 / Accepted: 14 April 2014 / Published: 12 May 2014
Cited by 11 | PDF Full-text (3686 KB) | HTML Full-text | XML Full-text
Abstract
One of the most distinctive and defining features of coleoid cephalopods—squid, cuttlefish and octopus—is their inking behavior. Their ink, which is blackened by melanin, but also contains other constituents, has been used by humans in various ways for millennia. This review summarizes [...] Read more.
One of the most distinctive and defining features of coleoid cephalopods—squid, cuttlefish and octopus—is their inking behavior. Their ink, which is blackened by melanin, but also contains other constituents, has been used by humans in various ways for millennia. This review summarizes our current knowledge of cephalopod ink. Topics include: (1) the production of ink, including the functional organization of the ink sac and funnel organ that produce it; (2) the chemical components of ink, with a focus on the best known of these—melanin and the biochemical pathways involved in its production; (3) the neuroecology of the use of ink in predator-prey interactions by cephalopods in their natural environment; and (4) the use of cephalopod ink by humans, including in the development of drugs for biomedical applications and other chemicals for industrial and other commercial applications. As is hopefully evident from this review, much is known about cephalopod ink and inking, yet more striking is how little we know. Towards closing that gap, future directions in research on cephalopod inking are suggested. Full article
(This article belongs to the collection Bioactive Compounds from Marine Invertebrates)
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Open AccessReview Evolving Marine Biomimetics for Regenerative Dentistry
Mar. Drugs 2014, 12(5), 2877-2912; doi:10.3390/md12052877
Received: 13 March 2014 / Revised: 14 April 2014 / Accepted: 16 April 2014 / Published: 13 May 2014
Cited by 4 | PDF Full-text (2301 KB) | HTML Full-text | XML Full-text
Abstract
New products that help make human tissue and organ regeneration more effective are in high demand and include materials, structures and substrates that drive cell-to-tissue transformations, orchestrate anatomical assembly and tissue integration with biology. Marine organisms are exemplary bioresources that have extensive [...] Read more.
New products that help make human tissue and organ regeneration more effective are in high demand and include materials, structures and substrates that drive cell-to-tissue transformations, orchestrate anatomical assembly and tissue integration with biology. Marine organisms are exemplary bioresources that have extensive possibilities in supporting and facilitating development of human tissue substitutes. Such organisms represent a deep and diverse reserve of materials, substrates and structures that can facilitate tissue reconstruction within lab-based cultures. The reason is that they possess sophisticated structures, architectures and biomaterial designs that are still difficult to replicate using synthetic processes, so far. These products offer tantalizing pre-made options that are versatile, adaptable and have many functions for current tissue engineers seeking fresh solutions to the deficiencies in existing dental biomaterials, which lack the intrinsic elements of biofunctioning, structural and mechanical design to regenerate anatomically correct dental tissues both in the culture dish and in vivo. Full article
(This article belongs to the Special Issue Marine Biomaterials)
Open AccessReview Conotoxins Targeting Nicotinic Acetylcholine Receptors: An Overview
Mar. Drugs 2014, 12(5), 2970-3004; doi:10.3390/md12052970
Received: 31 March 2014 / Revised: 24 April 2014 / Accepted: 28 April 2014 / Published: 22 May 2014
Cited by 22 | PDF Full-text (2428 KB) | HTML Full-text | XML Full-text
Abstract
Marine snails of the genus Conus are a large family of predatory gastropods with an unparalleled molecular diversity of pharmacologically active compounds in their venom. Cone snail venom comprises of a rich and diverse cocktail of peptide toxins which act on a [...] Read more.
Marine snails of the genus Conus are a large family of predatory gastropods with an unparalleled molecular diversity of pharmacologically active compounds in their venom. Cone snail venom comprises of a rich and diverse cocktail of peptide toxins which act on a wide variety of ion channels such as voltage-gated sodium- (NaV), potassium- (KV), and calcium- (CaV) channels as well as nicotinic acetylcholine receptors (nAChRs) which are classified as ligand-gated ion channels. The mode of action of several conotoxins has been the subject of investigation, while for many others this remains unknown. This review aims to give an overview of the knowledge we have today on the molecular pharmacology of conotoxins specifically interacting with nAChRs along with the structure–function relationship data. Full article
(This article belongs to the collection Bioactive Compounds from Marine Invertebrates)
Open AccessReview Fermentation Technologies for the Optimization of Marine Microbial Exopolysaccharide Production
Mar. Drugs 2014, 12(5), 3005-3024; doi:10.3390/md12053005
Received: 3 February 2014 / Revised: 2 April 2014 / Accepted: 3 April 2014 / Published: 22 May 2014
Cited by 10 | PDF Full-text (809 KB) | HTML Full-text | XML Full-text
Abstract
In the last decades, research has focused on the capabilities of microbes to secrete exopolysaccharides (EPS), because these polymers differ from the commercial ones derived essentially from plants or algae in their numerous valuable qualities. These biopolymers have emerged as new polymeric [...] Read more.
In the last decades, research has focused on the capabilities of microbes to secrete exopolysaccharides (EPS), because these polymers differ from the commercial ones derived essentially from plants or algae in their numerous valuable qualities. These biopolymers have emerged as new polymeric materials with novel and unique physical characteristics that have found extensive applications. In marine microorganisms the produced EPS provide an instrument to survive in adverse conditions: They are found to envelope the cells by allowing the entrapment of nutrients or the adhesion to solid substrates. Even if the processes of synthesis and release of exopolysaccharides request high-energy investments for the bacterium, these biopolymers permit resistance under extreme environmental conditions. Marine bacteria like Bacillus, Halomonas, Planococcus, Enterobacter, Alteromonas, Pseudoalteromonas, Vibrio, Rhodococcus, Zoogloea but also Archaea as Haloferax and Thermococcus are here described as EPS producers underlining biopolymer hyperproduction, related fermentation strategies including the effects of the chemical composition of the media, the physical parameters of the growth conditions and the genetic and predicted experimental design tools. Full article
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Open AccessReview Tipping Points in Seaweed Genetic Engineering: Scaling Up Opportunities in the Next Decade
Mar. Drugs 2014, 12(5), 3025-3045; doi:10.3390/md12053025
Received: 8 February 2014 / Revised: 4 April 2014 / Accepted: 25 April 2014 / Published: 22 May 2014
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Abstract
Seaweed genetic engineering is a transgenic expression system with unique features compared with those of heterotrophic prokaryotes and higher plants. This study discusses several newly sequenced seaweed nuclear genomes and the necessity that research on vector design should consider endogenous promoters, codon [...] Read more.
Seaweed genetic engineering is a transgenic expression system with unique features compared with those of heterotrophic prokaryotes and higher plants. This study discusses several newly sequenced seaweed nuclear genomes and the necessity that research on vector design should consider endogenous promoters, codon optimization, and gene copy number. Seaweed viruses and artificial transposons can be applied as transformation methods after acquiring a comprehensive understanding of the mechanism of viral infections in seaweeds and transposon patterns in seaweed genomes. After cultivating transgenic algal cells and tissues in a photobioreactor, a biosafety assessment of genetically modified (GM) seaweeds must be conducted before open-sea application. We propose a set of programs for the evaluation of gene flow from GM seaweeds to local/geographical environments. The effective implementation of such programs requires fundamentally systematic and interdisciplinary studies on algal physiology and genetics, marine hydrology, reproductive biology, and ecology. Full article

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