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Mar. Drugs, Volume 13, Issue 4 (April 2015), Pages 1621-2558

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Open AccessArticle Bioactive Secondary Metabolites from the Red Sea Marine Verongid Sponge Suberea Species
Mar. Drugs 2015, 13(4), 1621-1631; doi:10.3390/md13041621
Received: 17 January 2015 / Revised: 4 March 2015 / Accepted: 17 March 2015 / Published: 24 March 2015
Cited by 7 | PDF Full-text (407 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In a continuation of our efforts to identify bioactive compounds from Red Sea Verongid sponges, the organic extract of the sponge Suberea species afforded seven compounds including two new dibrominated alkaloids, subereamollines C and D (1 and 2), together with the
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In a continuation of our efforts to identify bioactive compounds from Red Sea Verongid sponges, the organic extract of the sponge Suberea species afforded seven compounds including two new dibrominated alkaloids, subereamollines C and D (1 and 2), together with the known compounds aerothionin (3), homoaerothionin (4), aeroplysinin-1 (5), aeroplysinin-2 (6) and a revised subereaphenol C (7) as ethyl 2-(2,4-dibromo-3,6-dihydroxyphenyl)acetate. The structures of the isolated compounds were assigned by different spectral data including optical rotations, 1D (1H and 13C) and 2D (COSY, multiplicity-edited HSQC, and HMBC) NMR and high-resolution mass spectroscopy. Aerothionin (3) and subereaphenol C (7) displayed potent cytotoxic activity against HeLa cell line with IC50 values of 29 and 13.3 µM, respectively. In addition, aeroplysinin-2 (6) showed potent antimigratory activity against the human breast cancer cell line MDA-MB-231 with IC50 of 18 µM. Subereamollines C and D are new congeners of the previously reported compounds subereamollines A and B with methyl ester functionalities on the side chain. These findings provide further insight into the biosynthetic capabilities of members of the genus Suberea and the chemical diversity as well as the biological activity of these compounds. Full article
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Open AccessCommunication Sulfated Steroid–Amino Acid Conjugates from the Irish Marine Sponge Polymastia boletiformis
Mar. Drugs 2015, 13(4), 1632-1646; doi:10.3390/md13041632
Received: 12 December 2014 / Revised: 23 February 2015 / Accepted: 16 March 2015 / Published: 24 March 2015
Cited by 3 | PDF Full-text (611 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Antifungal bioactivity-guided fractionation of the organic extract of the sponge Polymastia boletiformis, collected from the west coast of Ireland, led to the isolation of two new sulfated steroid-amino acid conjugates (1 and 2). Extensive 1D and 2D NMR analyses in
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Antifungal bioactivity-guided fractionation of the organic extract of the sponge Polymastia boletiformis, collected from the west coast of Ireland, led to the isolation of two new sulfated steroid-amino acid conjugates (1 and 2). Extensive 1D and 2D NMR analyses in combination with quantum mechanical calculations of the electronic circular dichroism (ECD) spectra, optical rotation, and 13C chemical shifts were used to establish the chemical structures of 1 and 2. Both compounds exhibited moderate antifungal activity against Cladosporium cucumerinum, while compound 2 was also active against Candida albicans. Marine natural products containing steroidal and amino acid constituents are extremely rare in nature. Full article
(This article belongs to the Special Issue Marine Anti-infective Agents)
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Open AccessArticle The Effect of Cholesterol on the Long-Range Network of Interactions Established among Sea Anemone Sticholysin II Residues at the Water-Membrane Interface
Mar. Drugs 2015, 13(4), 1647-1665; doi:10.3390/md13041647
Received: 23 January 2015 / Revised: 3 March 2015 / Accepted: 16 March 2015 / Published: 25 March 2015
Cited by 9 | PDF Full-text (1254 KB) | HTML Full-text | XML Full-text
Abstract
Actinoporins are α-pore forming proteins with therapeutic potential, produced by sea anemones. Sticholysin II (StnII) from Stichodactyla helianthus is one of its most extensively characterized members. These proteins remain stably folded in water, but upon interaction with lipid bilayers, they oligomerize to form
[...] Read more.
Actinoporins are α-pore forming proteins with therapeutic potential, produced by sea anemones. Sticholysin II (StnII) from Stichodactyla helianthus is one of its most extensively characterized members. These proteins remain stably folded in water, but upon interaction with lipid bilayers, they oligomerize to form a pore. This event is triggered by the presence of sphingomyelin (SM), but cholesterol (Chol) facilitates pore formation. Membrane attachment and pore formation require changes involving long-distance rearrangements of residues located at the protein-membrane interface. The influence of Chol on membrane recognition, oligomerization, and/or pore formation is now studied using StnII variants, which are characterized in terms of their ability to interact with model membranes in the presence or absence of Chol. The results obtained frame Chol not only as an important partner for SM for functional membrane recognition but also as a molecule which significantly reduces the structural requirements for the mentioned conformational rearrangements to occur. However, given that the DOPC:SM:Chol vesicles employed display phase coexistence and have domain boundaries, the observed effects could be also due to the presence of these different phases on the membrane. In addition, it is also shown that the Arg51 guanidinium group is strictly required for membrane recognition, independently of the presence of Chol. Full article
Open AccessArticle Occurrence of Lipophilic Marine Toxins in Shellfish from Galicia (NW of Spain) and Synergies among Them
Mar. Drugs 2015, 13(4), 1666-1687; doi:10.3390/md13041666
Received: 2 January 2015 / Revised: 25 February 2015 / Accepted: 10 March 2015 / Published: 25 March 2015
Cited by 5 | PDF Full-text (1121 KB) | HTML Full-text | XML Full-text
Abstract
Lipophilic marine toxins pose a serious threat for consumers and an enormous economic problem for shellfish producers. Synergistic interaction among toxins may play an important role in the toxicity of shellfish and consequently in human intoxications. In order to study the toxic profile
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Lipophilic marine toxins pose a serious threat for consumers and an enormous economic problem for shellfish producers. Synergistic interaction among toxins may play an important role in the toxicity of shellfish and consequently in human intoxications. In order to study the toxic profile of molluscs, sampled during toxic episodes occurring in different locations in Galicia in 2014, shellfish were analyzed by liquid chromatography tandem mass spectrometry (LC–MS/MS), the official method for the detection of lipophilic toxins. The performance of this procedure was demonstrated to be fit for purpose and was validated in house following European guidelines. The vast majority of toxins present in shellfish belonged to the okadaic acid (OA) group and some samples from a particular area contained yessotoxin (YTX). Since these toxins occur very often with other lipophilic toxins, we evaluated the potential interactions among them. A human neuroblastoma cell line was used to study the possible synergies of OA with other lipophilic toxins. Results show that combination of OA with dinophysistoxin 2 (DTX2) or YTX enhances the toxicity triggered by OA, decreasing cell viability and cell proliferation, depending on the toxin concentration and incubation time. The effects of other lipophilic toxins as 13-desmethyl Spirolide C were also evaluated in vitro. Full article
(This article belongs to the Special Issue Emerging Marine Toxins)
Open AccessArticle Identification and Bioactivity of Compounds from the Fungus Penicillium sp. CYE-87 Isolated from a Marine Tunicate
Mar. Drugs 2015, 13(4), 1698-1709; doi:10.3390/md13041698
Received: 26 December 2014 / Revised: 13 March 2015 / Accepted: 18 March 2015 / Published: 25 March 2015
Cited by 9 | PDF Full-text (592 KB) | HTML Full-text | XML Full-text
Abstract
In the course of our continuous interest in identifying bioactive compounds from marine microbes, we have investigated a tunicate-derived fungus, Penicillium sp. CYE-87. A new compound with the 1,4-diazepane skeleton, terretrione D (2), together with the known compounds, methyl-2-([2-(1H-indol-3-yl)ethyl]carbamoyl)acetate (1
[...] Read more.
In the course of our continuous interest in identifying bioactive compounds from marine microbes, we have investigated a tunicate-derived fungus, Penicillium sp. CYE-87. A new compound with the 1,4-diazepane skeleton, terretrione D (2), together with the known compounds, methyl-2-([2-(1H-indol-3-yl)ethyl]carbamoyl)acetate (1), tryptamine (3), indole-3-carbaldehyde (4), 3,6-diisobutylpyrazin-2(1H)-one (5) and terretrione C (6), were isolated from Penicillium sp. CYE-87. The structures of the isolated compounds were established by spectral analysis, including 1D (1H, 13C) and 2D (COSY, multiplicity edited-HSQC and HMBC) NMR and HRESIMS, as well as comparison of their NMR data with those in the literature. The compounds were evaluated for their antimigratory activity against the human breast cancer cell line (MDA-MB-231) and their antiproliferation activity against HeLa cells. Compounds 2 and 6 showed significant antimigratory activity against MDA-MB-231, as well as antifungal activity against C. albicans. Full article
(This article belongs to the Special Issue Bioactive Compounds from Marine Fungi)
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Open AccessArticle Influence of Molecular Weight and Degree of Deacetylation of Low Molecular Weight Chitosan on the Bioactivity of Oral Insulin Preparations
Mar. Drugs 2015, 13(4), 1710-1725; doi:10.3390/md13041710
Received: 10 December 2014 / Revised: 19 January 2015 / Accepted: 15 February 2015 / Published: 27 March 2015
Cited by 7 | PDF Full-text (922 KB) | HTML Full-text | XML Full-text
Abstract
The objective of the present study was to prepare and characterize low molecular weight chitosan (LMWC) with different molecular weight and degrees of deacetylation (DDA) and to optimize their use in oral insulin nano delivery systems. Water in oil nanosized systems containing LMWC-insulin
[...] Read more.
The objective of the present study was to prepare and characterize low molecular weight chitosan (LMWC) with different molecular weight and degrees of deacetylation (DDA) and to optimize their use in oral insulin nano delivery systems. Water in oil nanosized systems containing LMWC-insulin polyelectrolyte complexes were constructed and their ability to reduce blood glucose was assessed in vivo on diabetic rats. Upon acid depolymerization and testing by viscosity method, three molecular weights of LMWC namely, 1.3, 13 and 18 kDa were obtained. As for the DDA, three LMWCs of 55%, 80% and 100% DDA were prepared and characterized by spectroscopic methods for each molecular weight. The obtained LMWCs showed different morphological and in silico patterns. Following complexation of LMWCs with insulin, different aggregation sizes were obtained. Moreover, the in vivo tested formulations showed different activities of blood glucose reduction. The highest glucose reduction was achieved with 1.3 kDa LMWC of 55% DDA. The current study emphasizes the importance of optimizing the molecular weight along with the DDA of the incorporated LMWC in oral insulin delivery preparations in order to ensure the highest performance of such delivery systems. Full article
(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan) Printed Edition available
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Open AccessArticle Seco-Taondiol, an Unusual Meroterpenoid from the Chilean Seaweed Stypopodium flabelliforme and Its Gastroprotective Effect in Mouse Model
Mar. Drugs 2015, 13(4), 1726-1738; doi:10.3390/md13041726
Received: 22 January 2015 / Revised: 1 March 2015 / Accepted: 20 March 2015 / Published: 30 March 2015
Cited by 4 | PDF Full-text (566 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Ten known meroterpenoids and the new meroterpenoid 7 were isolated from the Chilean seaweed Stypopodium flabelliforme as their acetylated derivatives. Furthermore, the known metabolite taondiol has been isolated for the first time from this species. The molecular structure of the new metabolite was
[...] Read more.
Ten known meroterpenoids and the new meroterpenoid 7 were isolated from the Chilean seaweed Stypopodium flabelliforme as their acetylated derivatives. Furthermore, the known metabolite taondiol has been isolated for the first time from this species. The molecular structure of the new metabolite was determined by spectroscopic methods based on 1D- and 2D-NMR. Isolation of 7 represents a key step toward a better understanding of the biogenesis of this class of meroterpenoids. Among the meroditerpenoids isolated, stypodiol, isoepitaondiol, epitaondiol and sargaol exhibited gastroprotective activity on the HCl/Ethanol-induced gastric lesions model in mice. Regarding the mode of gastroprotective action, the activity of epitaondiol was reversed significantly when animals were pretreated with indomethacin, N-ethylmaleimide and N-nitro-l-arginine methyl ester (L-NAME) suggesting that prostaglandins, sulfhydryl groups and nitric oxide are involved in their mode of gastroprotective action. In the case of sargaol the gastroprotective activity was attenuated with indomethacin and N-ethylmaleimide, which suggests that prostaglandins and sulfhydryl groups are also involved in the mode of action using this model. Full article
(This article belongs to the Special Issue Marine Secondary Metabolites)
Open AccessArticle Co-Processed Chitin-Mannitol as a New Excipient for Oro-Dispersible Tablets
Mar. Drugs 2015, 13(4), 1739-1764; doi:10.3390/md13041739
Received: 2 November 2014 / Revised: 21 January 2015 / Accepted: 9 February 2015 / Published: 30 March 2015
Cited by 3 | PDF Full-text (1257 KB) | HTML Full-text | XML Full-text
Abstract
This study describes the preparation, characterization and performance of a novel excipient for use in oro-dispersible tablets (ODT). The excipient (CopCM) consists of chitin and mannitol. The excipient with optimal physicochemical properties was obtained at a chitin: mannitol ratio
[...] Read more.
This study describes the preparation, characterization and performance of a novel excipient for use in oro-dispersible tablets (ODT). The excipient (CopCM) consists of chitin and mannitol. The excipient with optimal physicochemical properties was obtained at a chitin: mannitol ratio of 2:8 (w/w) and produced by roll compaction (RC). Differential scanning calorimetry (DSC), Fourier transform-Infrared (FT-IR), X-ray powder diffraction (XRPD) and scanning electron microscope (SEM) techniques were used to characterize CopCM, in addition to characterization of its powder and ODT dosage form. The effect of particle size distribution of CopCM was investigated and found to have no significant influence on the overall tablet physical properties. The compressibility parameter (a) for CopCM was calculated from a Kawakita plot and found to be higher (0.661) than that of mannitol (0.576) due to the presence of the highly compressible chitin (0.818). Montelukast sodium and domperidone ODTs produced, using CopCM, displayed excellent physicochemical properties. The exceptional binding, fast wetting and superdisintegration properties of CopCM, in comparison with commercially available co-processed ODT excipients, results in a unique multifunctional base which can successfully be used in the formulation of oro-dispersible and fast immediate release tablets. Full article
(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan) Printed Edition available
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Open AccessArticle Low Molecular Weight Chitosan–Insulin Polyelectrolyte Complex: Characterization and Stability Studies
Mar. Drugs 2015, 13(4), 1765-1784; doi:10.3390/md13041765
Received: 17 December 2014 / Revised: 28 January 2015 / Accepted: 3 February 2015 / Published: 30 March 2015
Cited by 5 | PDF Full-text (671 KB) | HTML Full-text | XML Full-text
Abstract
The aim of the work reported herein was to investigate the effect of various low molecular weight chitosans (LMWCs) on the stability of insulin using USP HPLC methods. Insulin was found to be stable in a polyelectrolyte complex (PEC) consisting of insulin and
[...] Read more.
The aim of the work reported herein was to investigate the effect of various low molecular weight chitosans (LMWCs) on the stability of insulin using USP HPLC methods. Insulin was found to be stable in a polyelectrolyte complex (PEC) consisting of insulin and LMWC in the presence of a Tris-buffer at pH 6.5. In the presence of LMWC, the stability of insulin increased with decreasing molecular weight of LMWC; 13 kDa LMWC was the most efficient molecular weight for enhancing the physical and chemical stability of insulin. Solubilization of insulin-LMWC polyelectrolyte complex (I-LMWC PEC) in a reverse micelle (RM) system, administered to diabetic rats, results in an oral delivery system for insulin with acceptable bioactivity. Full article
(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan) Printed Edition available
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Open AccessArticle First Evidence that Ecklonia cava-Derived Dieckol Attenuates MCF-7 Human Breast Carcinoma Cell Migration
Mar. Drugs 2015, 13(4), 1785-1797; doi:10.3390/md13041785
Received: 1 February 2015 / Revised: 9 March 2015 / Accepted: 18 March 2015 / Published: 30 March 2015
Cited by 6 | PDF Full-text (677 KB) | HTML Full-text | XML Full-text
Abstract
We investigated the effect of Ecklonia cava (E. cava)-derived dieckol on movement behavior and the expression of migration-related genes in MCF-7 human breast cancer cell. Phlorotannins (e.g., dieckol, 6,6′-biecko, and 2,7″-phloroglucinol-6,6′-bieckol) were purified from E. cava by using centrifugal partition chromatography. Among
[...] Read more.
We investigated the effect of Ecklonia cava (E. cava)-derived dieckol on movement behavior and the expression of migration-related genes in MCF-7 human breast cancer cell. Phlorotannins (e.g., dieckol, 6,6′-biecko, and 2,7″-phloroglucinol-6,6′-bieckol) were purified from E. cava by using centrifugal partition chromatography. Among the phlorotannins, we found that dieckol inhibited breast cancer cell the most and was selected for further study. Radius™-well was used to assess cell migration, and dieckol (1–100 µM) was found to suppress breast cancer cell movement. Metastasis-related gene expressions were evaluated by RT-PCR and Western blot analysis. In addition, dieckol inhibited the expression of migration-related genes such as matrix metalloproteinase (MMP)-9 and vascular endothelial growth factor (VEGF). On the other hand, it stimulated the expression of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. These results suggest that dieckol exerts anti-breast cancer activity via the regulation of the expressions of metastasis-related genes, and this is the first report on the anti-breast cancer effect of dieckol. Full article
(This article belongs to the collection Marine Compounds and Cancer) Printed Edition available
Open AccessArticle Morphological and Proteomic Analyses Reveal that Unsaturated Guluronate Oligosaccharide Modulates Multiple Functional Pathways in Murine Macrophage RAW264.7 Cells
Mar. Drugs 2015, 13(4), 1798-1818; doi:10.3390/md13041798
Received: 5 February 2015 / Revised: 15 March 2015 / Accepted: 20 March 2015 / Published: 30 March 2015
Cited by 5 | PDF Full-text (1375 KB) | HTML Full-text | XML Full-text
Abstract
Alginate is a natural polysaccharide extracted from various species of marine brown algae. Alginate-derived guluronate oligosaccharide (GOS) obtained by enzymatic depolymerization has various pharmacological functions. Previous studies have demonstrated that GOS can trigger the production of inducible nitric oxide synthase (iNOS)/nitric oxide (NO),
[...] Read more.
Alginate is a natural polysaccharide extracted from various species of marine brown algae. Alginate-derived guluronate oligosaccharide (GOS) obtained by enzymatic depolymerization has various pharmacological functions. Previous studies have demonstrated that GOS can trigger the production of inducible nitric oxide synthase (iNOS)/nitric oxide (NO), reactive oxygen species (ROS) and tumor necrosis factor (TNF)-α by macrophages and that it is involved in the nuclear factor (NF)-κB and mitogen-activated protein (MAP) kinase signaling pathways. To expand upon the current knowledge regarding the molecular mechanisms associated with the GOS-induced immune response in macrophages, comparative proteomic analysis was employed together with two-dimensional electrophoresis (2-DE), matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/TOF MS) and Western blot verification. Proteins showing significant differences in expression in GOS-treated cells were categorized into multiple functional pathways, including the NF-κB signaling pathway and pathways involved in inflammation, antioxidant activity, glycolysis, cytoskeletal processes and translational elongation. Moreover, GOS-stimulated changes in the morphologies and actin cytoskeleton organization of RAW264.7 cells were also investigated as possible adaptations to GOS. This study is the first to reveal GOS as a promising agent that can modulate the proper balance between the pro- and anti-inflammatory immune responses, and it provides new insights into pharmaceutical applications of polysaccharides. Full article
(This article belongs to the collection Marine Polysaccharides)
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Open AccessArticle Dietary Docosahexaenoic Acid and Eicosapentaenoic Acid Influence Liver Triacylglycerol and Insulin Resistance in Rats Fed a High-Fructose Diet
Mar. Drugs 2015, 13(4), 1864-1881; doi:10.3390/md13041864
Received: 9 February 2015 / Revised: 10 March 2015 / Accepted: 23 March 2015 / Published: 1 April 2015
Cited by 13 | PDF Full-text (796 KB) | HTML Full-text | XML Full-text
Abstract
This study aimed to examine the benefits of different amounts of omega-3 (n-3) polyunsaturated fatty acids from fish oil (FO) on lipid metabolism, insulin resistance and gene expression in rats fed a high-fructose diet. Male Wistar rats were separated into two
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This study aimed to examine the benefits of different amounts of omega-3 (n-3) polyunsaturated fatty acids from fish oil (FO) on lipid metabolism, insulin resistance and gene expression in rats fed a high-fructose diet. Male Wistar rats were separated into two groups: Control (C, n = 6) and Fructose (Fr, n = 32), the latter receiving a diet containing 63% by weight fructose for 60 days. After this period, 24 animals from Fr group were allocated to three groups: FrFO2 (n = 8) receiving 63% fructose and 2% FO plus 5% soybean oil; FrFO5 (n = 8) receiving 63% fructose and 5% FO plus 2% soybean oil; and FrFO7 (n = 8) receiving 63% fructose and 7% FO. Animals were fed these diets for 30 days. Fructose led to an increase in liver weight, hepatic and serum triacylglycerol, serum alanine aminotransferase and HOMA1-IR index. These alterations were reversed by 5% and 7% FO. FO had a dose-dependent effect on expression of genes related to hepatic β-oxidation (increased) and hepatic lipogenesis (decreased). The group receiving the highest FO amount had increased markers of oxidative stress. It is concluded that n-3 fatty acids may be able to reverse the adverse metabolic effects induced by a high fructose diet. Full article
(This article belongs to the Special Issue Marine Lipids)
Open AccessArticle Prophylactic Administration of Fucoidan Represses Cancer Metastasis by Inhibiting Vascular Endothelial Growth Factor (VEGF) and Matrix Metalloproteinases (MMPs) in Lewis Tumor-Bearing Mice
Mar. Drugs 2015, 13(4), 1882-1900; doi:10.3390/md13041882
Received: 12 February 2015 / Revised: 26 March 2015 / Accepted: 27 March 2015 / Published: 3 April 2015
Cited by 18 | PDF Full-text (883 KB) | HTML Full-text | XML Full-text
Abstract
Fucoidan, a heparin-like sulfated polysaccharide, is rich in brown algae. It has a wide assortment of protective activities against cancer, for example, induction of hepatocellular carcinoma senescence, induction of human breast and colon carcinoma apoptosis, and impediment of lung cancer cells migration and
[...] Read more.
Fucoidan, a heparin-like sulfated polysaccharide, is rich in brown algae. It has a wide assortment of protective activities against cancer, for example, induction of hepatocellular carcinoma senescence, induction of human breast and colon carcinoma apoptosis, and impediment of lung cancer cells migration and invasion. However, the anti-metastatic mechanism that fucoidan exploits remains elusive. In this report, we explored the effects of fucoidan on cachectic symptoms, tumor development, lung carcinoma cell spreading and proliferation, as well as expression of metastasis-associated proteins in the Lewis lung carcinoma (LLC) cells-inoculated mice model. We discovered that administration of fucoidan has prophylactic effects on mitigation of cachectic body weight loss and improvement of lung masses in tumor-inoculated mice. These desired effects are attributed to inhibition of LLC spreading and proliferation in lung tissues. Fucoidan also down-regulates expression of matrix metalloproteinases (MMPs), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and vascular endothelial growth factor (VEGF). Moreover, the tumor-bearing mice supplemented with fucoidan indeed benefit from an ensemble of the chemo-phylacticity. The fact is that fucoidan significantly decreases viability, migration, invasion, and MMPs activities of LLC cells. In summary, fucoidan is suitable to act as a chemo-preventative agent for minimizing cachectic symptoms as well as inhibiting lung carcinoma metastasis through down-regulating metastatic factors VEGF and MMPs. Full article
(This article belongs to the collection Marine Polysaccharides)
Open AccessArticle 3-[4-(1H-Indol-3-yl)-1,3-thiazol-2-yl]-1H-pyrrolo[2,3-b]pyridines, Nortopsentin Analogues with Antiproliferative Activity
Mar. Drugs 2015, 13(4), 1901-1924; doi:10.3390/md13041901
Received: 22 February 2015 / Revised: 22 March 2015 / Accepted: 25 March 2015 / Published: 3 April 2015
Cited by 20 | PDF Full-text (919 KB) | HTML Full-text | XML Full-text
Abstract
A new series of nortopsentin analogues, in which the imidazole ring of the natural product was replaced by thiazole and the indole unit bound to position 2 of the thiazole ring was substituted by a 7-azaindole moiety, was efficiently synthesized. Two of the
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A new series of nortopsentin analogues, in which the imidazole ring of the natural product was replaced by thiazole and the indole unit bound to position 2 of the thiazole ring was substituted by a 7-azaindole moiety, was efficiently synthesized. Two of the new nortopsentin analogues showed good antiproliferative effect against the totality of the NCI full panel of human tumor cell lines (~60) having GI50 values ranging from low micromolar to nanomolar level. The mechanism of the antiproliferative effect of these derivatives, investigated on human hepatoma HepG2 cells, was pro-apoptotic, being associated with externalization of plasma membrane phosphatidylserine and mitochondrial dysfunction. Moreover, the compounds induced a concentration-dependent accumulation of cells in the subG0/G1phase, while confined viable cells in G2/M phase. Full article
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Open AccessArticle Two Novel Antioxidant Nonapeptides from Protein Hydrolysate of Skate (Raja porosa) Muscle
Mar. Drugs 2015, 13(4), 1993-2009; doi:10.3390/md13041993
Received: 21 January 2015 / Revised: 25 March 2015 / Accepted: 26 March 2015 / Published: 3 April 2015
Cited by 5 | PDF Full-text (575 KB) | HTML Full-text | XML Full-text
Abstract
In the current study, the preparation conditions of neutrase hydrolysate (SMH) from skate (Raja porosa) muscle protein were optimized using orthogonal L9(3)4 tests, and R values indicated that pH was the most important factor affecting HO· scavenging activity
[...] Read more.
In the current study, the preparation conditions of neutrase hydrolysate (SMH) from skate (Raja porosa) muscle protein were optimized using orthogonal L9(3)4 tests, and R values indicated that pH was the most important factor affecting HO· scavenging activity of SMH. Under the optimum conditions of pH 7.0, enzymolysis temperature 60 °C, enzyme/substrate ratio (E/S) 2%, and enzymolysis time 5 h, EC50 of SMH on HO· was 2.14 ± 0.17 mg/mL. Using ultrafiltration, gel filtration chromatography, and RP-HPLC, two novel antioxidant nonapeptides (SP-A and SP-B) were isolated from SMH and their amino acid sequences were found to be APPTAYAQS (SP-A) and NWDMEKIWD (SP-B) with calculated molecular masses of 904.98 Da and 1236.38 Da, respectively. Both showed strong antioxidant activities. SP-A and SP-B exhibited good scavenging activities on HO· (EC50 0.390 and 0.176 mg/mL), DPPH· (EC50 0.614 and 0.289 mg/mL), and O2· (EC50 0.215 and 0.132 mg/mL) in a dose-dependent manner. SP-B was also effective against lipid peroxidation in the model system. The aromatic (2Trp), acidic (2Asp and Glu), and basic (Lys) amino acid residues within the sequences of SP-B might account for its pronounced antioxidant activity. The results of this study suggested that protein hydrolysate and peptides from skate muscle might be effective as food additives for retarding lipid peroxidation occurring in foodstuffs. Full article
(This article belongs to the Special Issue Marine Peptides and Their Mimetics)
Open AccessArticle Inhibition of N-Type Calcium Channels by Fluorophenoxyanilide Derivatives
Mar. Drugs 2015, 13(4), 2030-2045; doi:10.3390/md13042030
Received: 21 February 2015 / Revised: 18 March 2015 / Accepted: 26 March 2015 / Published: 13 April 2015
Cited by 3 | PDF Full-text (481 KB) | HTML Full-text | XML Full-text
Abstract
A set of fluorophenoxyanilides, designed to be simplified analogues of previously reported ω-conotoxin GVIA mimetics, were prepared and tested for N-type calcium channel inhibition in a SH-SY5Y neuroblastoma FLIPR assay. N-type or Cav2.2 channel is a validated target for the treatment
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A set of fluorophenoxyanilides, designed to be simplified analogues of previously reported ω-conotoxin GVIA mimetics, were prepared and tested for N-type calcium channel inhibition in a SH-SY5Y neuroblastoma FLIPR assay. N-type or Cav2.2 channel is a validated target for the treatment of refractory chronic pain. Despite being significantly less complex than the originally designed mimetics, up to a seven-fold improvement in activity was observed. Full article
(This article belongs to the Special Issue Marine Peptides and Their Mimetics)
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Open AccessArticle Toxin Profile of Gymnodinium catenatum (Dinophyceae) from the Portuguese Coast, as Determined by Liquid Chromatography Tandem Mass Spectrometry
Mar. Drugs 2015, 13(4), 2046-2062; doi:10.3390/md13042046
Received: 11 December 2014 / Revised: 16 March 2015 / Accepted: 27 March 2015 / Published: 13 April 2015
Cited by 2 | PDF Full-text (821 KB) | HTML Full-text | XML Full-text
Abstract
The marine dinoflagellate Gymnodinium catenatum has been associated with paralytic shellfish poisoning (PSP) outbreaks in Portuguese waters for many years. PSP syndrome is caused by consumption of seafood contaminated with paralytic shellfish toxins (PSTs), a suite of potent neurotoxins. Gymnodinium catenatum was frequently
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The marine dinoflagellate Gymnodinium catenatum has been associated with paralytic shellfish poisoning (PSP) outbreaks in Portuguese waters for many years. PSP syndrome is caused by consumption of seafood contaminated with paralytic shellfish toxins (PSTs), a suite of potent neurotoxins. Gymnodinium catenatum was frequently reported along the Portuguese coast throughout the late 1980s and early 1990s, but was absent between 1995 and 2005. Since this time, G. catenatum blooms have been recurrent, causing contamination of fishery resources along the Atlantic coast of Portugal. The aim of this study was to evaluate the toxin profile of G. catenatum isolated from the Portuguese coast before and after the 10-year hiatus to determine changes and potential impacts for the region. Hydrophilic interaction liquid chromatography tandem mass spectrometry (HILIC-MS/MS) was utilized to determine the presence of any known and emerging PSTs in sample extracts. Several PST derivatives were identified, including the N-sulfocarbamoyl analogues (C1–4), gonyautoxin 5 (GTX5), gonyautoxin 6 (GTX6), and decarbamoyl derivatives, decarbamoyl saxitoxin (dcSTX), decarbamoyl neosaxitoxin (dcNeo) and decarbamoyl gonyautoxin 3 (dcGTX3). In addition, three known hydroxy benzoate derivatives, G. catenatum toxin 1 (GC1), GC2 and GC3, were confirmed in cultured and wild strains of G. catenatum. Moreover, two presumed N-hydroxylated analogues of GC2 and GC3, designated GC5 and GC6, are reported. This work contributes to our understanding of the toxigenicity of G. catenatum in the coastal waters of Portugal and provides valuable information on emerging PST classes that may be relevant for routine monitoring programs tasked with the prevention and control of marine toxins in fish and shellfish. Full article
(This article belongs to the Special Issue Marine Shellfish Toxins)
Open AccessArticle Structural Analysis and Anticoagulant Activities of the Novel Sulfated Fucan Possessing a Regular Well-Defined Repeating Unit from Sea Cucumber
Mar. Drugs 2015, 13(4), 2063-2084; doi:10.3390/md13042063
Received: 26 January 2015 / Revised: 25 March 2015 / Accepted: 26 March 2015 / Published: 13 April 2015
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Abstract
Sulfated fucans, the complex polysaccharides, exhibit various biological activities. Herein, we purified two fucans from the sea cucumbers Holothuria edulis and Ludwigothurea grisea. Their structures were verified by means of HPGPC, FT-IR, GC–MS and NMR. As a result, a novel structural motif
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Sulfated fucans, the complex polysaccharides, exhibit various biological activities. Herein, we purified two fucans from the sea cucumbers Holothuria edulis and Ludwigothurea grisea. Their structures were verified by means of HPGPC, FT-IR, GC–MS and NMR. As a result, a novel structural motif for this type of polymers is reported. The fucans have a unique structure composed of a central core of regular (1→2) and (1→3)-linked tetrasaccharide repeating units. Approximately 50% of the units from L. grisea (100% for H. edulis fucan) contain sides of oligosaccharides formed by nonsulfated fucose units linked to the O-4 position of the central core. Anticoagulant activity assays indicate that the sea cucumber fucans strongly inhibit human blood clotting through the intrinsic pathways of the coagulation cascade. Moreover, the mechanism of anticoagulant action of the fucans is selective inhibition of thrombin activity by heparin cofactor II. The distinctive tetrasaccharide repeating units contribute to the anticoagulant action. Additionally, unlike the fucans from marine alga, although the sea cucumber fucans have great molecular weights and affluent sulfates, they do not induce platelet aggregation. Overall, our results may be helpful in understanding the structure-function relationships of the well-defined polysaccharides from invertebrate as new types of safer anticoagulants. Full article
(This article belongs to the collection Marine Polysaccharides)
Open AccessArticle Studies toward the Total Synthesis of Itralamide B and Biological Evaluation of Its Structural Analogs
Mar. Drugs 2015, 13(4), 2085-2104; doi:10.3390/md13042085
Received: 8 February 2015 / Revised: 17 March 2015 / Accepted: 30 March 2015 / Published: 13 April 2015
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Abstract
Itralamides A and B were isolated from the lipophilic extract of Lyngbya majuscula collected from the eastern Caribbean. Itralamide B (1) showed cytotoxic activity towards human embryonic kidney cells (HEK293, IC50 = 6 μM). Preliminary studies disapproved the proposed stereochemistry
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Itralamides A and B were isolated from the lipophilic extract of Lyngbya majuscula collected from the eastern Caribbean. Itralamide B (1) showed cytotoxic activity towards human embryonic kidney cells (HEK293, IC50 = 6 μM). Preliminary studies disapproved the proposed stereochemistry of itralamide. In this paper, we will provide a full account of the total synthesis of four stereoisomers of itralamide B and the results derived from biological tests of these structural congeners. Full article
(This article belongs to the Special Issue Marine Peptides and Their Mimetics)
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Open AccessArticle Astaxanthin Attenuates Early Acute Kidney Injury Following Severe Burns in Rats by Ameliorating Oxidative Stress and Mitochondrial-Related Apoptosis
Mar. Drugs 2015, 13(4), 2105-2123; doi:10.3390/md13042105
Received: 24 December 2014 / Revised: 18 March 2015 / Accepted: 31 March 2015 / Published: 13 April 2015
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Abstract
Early acute kidney injury (AKI) is a devastating complication in critical burn patients, and it is associated with severe morbidity and mortality. The mechanism of AKI is multifactorial. Astaxanthin (ATX) is a natural compound that is widely distributed in marine organisms; it is
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Early acute kidney injury (AKI) is a devastating complication in critical burn patients, and it is associated with severe morbidity and mortality. The mechanism of AKI is multifactorial. Astaxanthin (ATX) is a natural compound that is widely distributed in marine organisms; it is a strong antioxidant and exhibits other biological effects that have been well studied in various traumatic injuries and diseases. Hence, we attempted to explore the potential protection of ATX against early post burn AKI and its possible mechanisms of action. The classic severe burn rat model was utilized for the histological and biochemical assessments of the therapeutic value and mechanisms of action of ATX. Upon ATX treatment, renal tubular injury and the levels of serum creatinine and neutrophil gelatinase-associated lipocalin were improved. Furthermore, relief of oxidative stress and tubular apoptosis in rat kidneys post burn was also observed. Additionally, ATX administration increased Akt and Bad phosphorylation and further down-regulated the expression of other downstream pro-apoptotic proteins (cytochrome c and caspase-3/9); these effects were reversed by the PI3K inhibitor LY294002. Moreover, the protective effect of ATX presents a dose-dependent enhancement. The data above suggested that ATX protects against early AKI following severe burns in rats, which was attributed to its ability to ameliorate oxidative stress and inhibit apoptosis by modulating the mitochondrial-apoptotic pathway, regarded as the Akt/Bad/Caspases signalling cascade. Full article
Open AccessArticle Antifungal Compounds from Cyanobacteria
Mar. Drugs 2015, 13(4), 2124-2140; doi:10.3390/md13042124
Received: 30 January 2015 / Revised: 24 March 2015 / Accepted: 26 March 2015 / Published: 13 April 2015
Cited by 11 | PDF Full-text (1004 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Cyanobacteria are photosynthetic prokaryotes found in a range of environments. They are infamous for the production of toxins, as well as bioactive compounds, which exhibit anticancer, antimicrobial and protease inhibition activities. Cyanobacteria produce a broad range of antifungals belonging to structural classes, such
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Cyanobacteria are photosynthetic prokaryotes found in a range of environments. They are infamous for the production of toxins, as well as bioactive compounds, which exhibit anticancer, antimicrobial and protease inhibition activities. Cyanobacteria produce a broad range of antifungals belonging to structural classes, such as peptides, polyketides and alkaloids. Here, we tested cyanobacteria from a wide variety of environments for antifungal activity. The potent antifungal macrolide scytophycin was detected in Anabaena sp. HAN21/1, Anabaena cf. cylindrica PH133, Nostoc sp. HAN11/1 and Scytonema sp. HAN3/2. To our knowledge, this is the first description of Anabaena strains that produce scytophycins. We detected antifungal glycolipopeptide hassallidin production in Anabaena spp. BIR JV1 and HAN7/1 and in Nostoc spp. 6sf Calc and CENA 219. These strains were isolated from brackish and freshwater samples collected in Brazil, the Czech Republic and Finland. In addition, three cyanobacterial strains, Fischerella sp. CENA 298, Scytonema hofmanni PCC 7110 and Nostoc sp. N107.3, produced unidentified antifungal compounds that warrant further characterization. Interestingly, all of the strains shown to produce antifungal compounds in this study belong to Nostocales or Stigonematales cyanobacterial orders. Full article
Open AccessArticle Diphlorethohydroxycarmalol Inhibits Interleukin-6 Production by Regulating NF-κB, STAT5 and SOCS1 in Lipopolysaccharide-Stimulated RAW264.7 Cells
Mar. Drugs 2015, 13(4), 2141-2157; doi:10.3390/md13042141
Received: 1 January 2015 / Revised: 9 March 2015 / Accepted: 30 March 2015 / Published: 13 April 2015
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Abstract
Diphlorethohydroxycarmalol (DPHC) is a phlorotannin compound isolated from Ishige okamuarae, a brown alga. This study was conducted to investigate the anti-inflammatory effect and action mechanism of DPHC in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. We found that DPHC strongly reduces the production of
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Diphlorethohydroxycarmalol (DPHC) is a phlorotannin compound isolated from Ishige okamuarae, a brown alga. This study was conducted to investigate the anti-inflammatory effect and action mechanism of DPHC in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. We found that DPHC strongly reduces the production of interleukin 6 (IL-6), but not that of tumor necrosis factor-alpha (TNF-α) induced by LPS. DPHC (12.5 and 100 μM) suppressed the phosphorylation and the nuclear translocation of NF-kappaB (NF-κB), a central signaling molecule in the inflammation process induced by LPS. The suppressor of cytokine signaling 1 (SOCS1) is a negative feedback regulator of Janus kinase (Jak)-signal transducer and activator of transcription (STAT) signaling. In this study, DPHC inhibited STAT5 expression and upregulated that of SOCS1 at a concentration of 100 μM. Furthermore, N-tosyl-l-phenylalanine chloromethyl ketone (TPCK) (a specific NF-κB inhibitor) and JI (a specific Jak2 inhibitor) reduced the production of IL-6, but not that of tumor necrosis factor-alpha (TNF-α) in LPS-stimulated RAW 264.7 macrophages. These findings demonstrate that DPHC inhibits IL-6 production via the downregulation of NF-κB and Jak2-STAT5 pathway and upregulation of SOCS1. Full article
Open AccessArticle Functional Recombinants Designed from a Fetuin/Asialofetuin-Specific Marine Algal Lectin, Rhodobindin
Mar. Drugs 2015, 13(4), 2183-2195; doi:10.3390/md13042183
Received: 10 February 2015 / Revised: 24 March 2015 / Accepted: 27 March 2015 / Published: 13 April 2015
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Abstract
Plant lectins have attracted much attention for biomedical applications including targeted drug delivery system and therapy against tumors and microbial infections. The main problem of using lectins as a biomedical tool is a batch-to-batch variation in isoforms content. The production of lectins using
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Plant lectins have attracted much attention for biomedical applications including targeted drug delivery system and therapy against tumors and microbial infections. The main problem of using lectins as a biomedical tool is a batch-to-batch variation in isoforms content. The production of lectins using recombination tools has the advantage of obtaining high amounts of proteins with more precise properties, but there are only a handful of functional recombinant lectins presently available. A fetuin/asialo-fetuin specific lectin, Rhodobindin, has unique tandem repeats structure which makes it useful in exploiting for recombinant lectin. We developed three functional recombinant lectins using E. coli expression system: one from full cDNA sequence and two from fragmentary sequences of Rhodobindin. Hemagglutinating activity and solubility of the recombinant lectins were highest at OD 0.7 cell concentration at 20 °C. The optimized process developed in this study was suitable for the quality-controlled production of high amounts of soluble recombinant lectins. Full article
Open AccessArticle Hyperoxia Elevates Adrenic Acid Peroxidation in Marine Fish and Is Associated with Reproductive Pheromone Mediators
Mar. Drugs 2015, 13(4), 2215-2232; doi:10.3390/md13042215
Received: 5 February 2015 / Revised: 25 March 2015 / Accepted: 1 April 2015 / Published: 14 April 2015
Cited by 3 | PDF Full-text (1354 KB) | HTML Full-text | XML Full-text
Abstract
The development of oxidative stress in the marine ecosystem is a concurring concern in fish reproductive behavior. Marine fish being rich in polyunsaturated fatty acids (PUFA) are precursors of prostaglandin pheromone mediators but also vulnerable to lipid peroxidation. It is yet to be
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The development of oxidative stress in the marine ecosystem is a concurring concern in fish reproductive behavior. Marine fish being rich in polyunsaturated fatty acids (PUFA) are precursors of prostaglandin pheromone mediators but also vulnerable to lipid peroxidation. It is yet to be determined if hypoxia or hyperoxia environment, a cumulative effect in the marine ecosystem affect pheromone mediators in fish, and to understand if this is associated with the generation of oxidized lipid products of PUFA. Novel oxidized lipid metabolites, isoprostanoids (15-F2t-isoprostane, 7(RS)-7-F2t-dihomo-isoprostane, 17(RS)-17-F2t-dihomo-isoprostane, 8-F3t-isoprostane, 4(RS)-4-F4t-neuroprostane, 10-F4t-neuroprostane), isofuranoids (isofurans, 10-epi-17(RS)-SC-Δ15-11-dihomo-isofuran and neurofurans), hydroxyeicosatetraenoic acids and resolvins, PUFA (arachidonic, adrenic, eicosapentaenoic and docosahexaenoic acids) and prostaglandin pheromone mediators in fish muscle were determined in marine male and female fish muscles before and after interaction in a hypoxia or hyperoxia environment. Reproductive behaviors were also assessed. Our study showed oxidized lipid metabolites of arachidonic, eicosapentaenoic, and docosahexaenoic acids were not influenced by hypoxia and hyperoxia exposure in the fishes and no gender differences were found. However, adrenic acid and its oxidized products, 17(RS)-17-F2t-dihomo-isoprostane and 10-epi-17(RS)-SC-Δ15-11-dihomo-isofuran showed strong correspondence with male fish pheromone mediators and reproductive behavior when under oxidative stress especially, hyperoxia. The occurrence of hypoxia and hyperoxia in the marine ecosystem may not be detrimental to marine fish and instead presents as being beneficial in reproductive behavior. Full article
(This article belongs to the Special Issue Marine Lipids)
Open AccessArticle Molecular and Chemical Analysis of the Lipopolysaccharide from Aeromonas hydrophila Strain AH-1 (Serotype O11)
Mar. Drugs 2015, 13(4), 2233-2249; doi:10.3390/md13042233
Received: 27 February 2015 / Revised: 30 March 2015 / Accepted: 7 April 2015 / Published: 14 April 2015
Cited by 6 | PDF Full-text (739 KB) | HTML Full-text | XML Full-text
Abstract
A group of virulent Aeromonas hydrophila, A. sobria, and A. veronii biovar sobria strains isolated from humans and fish have been described; these strains classified to serotype O11 are serologically related by their lipopolysaccharide (LPS) O-antigen (O-polysaccharide), and
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A group of virulent Aeromonas hydrophila, A. sobria, and A. veronii biovar sobria strains isolated from humans and fish have been described; these strains classified to serotype O11 are serologically related by their lipopolysaccharide (LPS) O-antigen (O-polysaccharide), and the presence of an S-layer consisting of multiple copies of a crystalline surface array protein with a molecular weight of 52 kDa in the form of a crystalline surface array which lies peripheral to the cell wall. A. hydrophila strain AH-1 is one of them. We isolated the LPS from this strain and determined the structure of the O-polysaccharide, which was similar to that previously described for another strain of serotype O11. The genetics of the O11-antigen showed the genes (wbO11 cluster) in two sections separated by genes involved in biosynthesis and assembly of the S-layer. The O11-antigen LPS is an example of an ABC-2-transporter-dependent pathway for O-antigen heteropolysaccharide (disaccharide) assembly. The genes involved in the biosynthesis of the LPS core (waaO11 cluster) were also identified in three different chromosome regions being nearly identical to the ones described for A. hydrophila AH-3 (serotype O34). The genetic data and preliminary chemical analysis indicated that the LPS core for strain AH-1 is identical to the one for strain AH-3. Full article
(This article belongs to the Special Issue Marine Lipopolysaccharides)
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Open AccessArticle Neuroprotective Effects of the Cultivated Chondrus crispus in a C. elegans Model of Parkinson’s Disease
Mar. Drugs 2015, 13(4), 2250-2266; doi:10.3390/md13042250
Received: 30 January 2015 / Revised: 30 March 2015 / Accepted: 1 April 2015 / Published: 14 April 2015
Cited by 7 | PDF Full-text (944 KB) | HTML Full-text | XML Full-text
Abstract
Parkinson’s disease (PD) is the second most common neurodegenerative disorder in the elderly people, currently with no cure. Its mechanisms are not well understood, thus studies targeting cause-directed therapy or prevention are needed. This study uses the transgenic Caenorhabditis elegans PD model. We
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Parkinson’s disease (PD) is the second most common neurodegenerative disorder in the elderly people, currently with no cure. Its mechanisms are not well understood, thus studies targeting cause-directed therapy or prevention are needed. This study uses the transgenic Caenorhabditis elegans PD model. We demonstrated that dietary supplementation of the worms with an extract from the cultivated red seaweed Chondrus crispus decreased the accumulation of α-synulein and protected the worms from the neuronal toxin-, 6-OHDA, induced dopaminergic neurodegeneration. These effects were associated with a corrected slowness of movement. We also showed that the enhancement of oxidative stress tolerance and an up-regulation of the stress response genes, sod-3 and skn-1, may have served as the molecular mechanism for the C. crispus-extract-mediated protection against PD pathology. Altogether, apart from its potential as a functional food, the tested red seaweed, C. crispus, might find promising pharmaceutical applications for the development of potential novel anti-neurodegenerative drugs for humans. Full article
(This article belongs to the Special Issue Marine Functional Food)
Open AccessArticle Esters of the Marine-Derived Triterpene Sipholenol A Reverse P-GP-Mediated Drug Resistance
Mar. Drugs 2015, 13(4), 2267-2286; doi:10.3390/md13042267
Received: 2 February 2015 / Revised: 10 March 2015 / Accepted: 25 March 2015 / Published: 14 April 2015
Cited by 8 | PDF Full-text (1071 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Our previous studies showed that several sipholane triterpenes, sipholenol A, sipholenone E, sipholenol L and siphonellinol D, have potent reversal effect for multidrug resistance (MDR) in cancer cells that overexpressed P-glycoprotein (P-gp/ABCB1). Through comparison of cytotoxicity towards sensitive and multi-drug resistant cell lines,
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Our previous studies showed that several sipholane triterpenes, sipholenol A, sipholenone E, sipholenol L and siphonellinol D, have potent reversal effect for multidrug resistance (MDR) in cancer cells that overexpressed P-glycoprotein (P-gp/ABCB1). Through comparison of cytotoxicity towards sensitive and multi-drug resistant cell lines, we identified that the semisynthetic esters sipholenol A-4-O-acetate and sipholenol A-4-O-isonicotinate potently reversed P-gp-mediated MDR but had no effect on MRP1/ABCC1 and BCRP/ABCG2-mediated MDR. The results from [3H]-paclitaxel accumulation and efflux studies suggested that these two triterpenoids were able to increase the intracellular accumulation of paclitaxel by inhibiting its active efflux. In addition, western blot analysis revealed that these two compounds did not alter the expression levels of P-gp when treated up to 72 h. These sipholenol derivatives also stimulated the ATPase activity of P-gp membranes, which suggested that they might be substrates of P-gp. Moreover, in silico molecular docking studies revealed the virtual binding modes of these two compounds into human homology model of P-gp. In conclusion, sipholenol A-4-O-acetate and sipholenol A-4-O-isonicotinate efficiently inhibit the P-gp and may represent potential reversal agents for the treatment of multidrug resistant cancers. Full article
(This article belongs to the collection Marine Compounds and Cancer) Printed Edition available
Open AccessArticle Piscidin is Highly Active against Carbapenem-Resistant Acinetobacter baumannii and NDM-1-Producing Klebsiella pneumonia in a Systemic Septicaemia Infection Mouse Model
Mar. Drugs 2015, 13(4), 2287-2305; doi:10.3390/md13042287
Received: 1 March 2015 / Revised: 30 March 2015 / Accepted: 1 April 2015 / Published: 14 April 2015
Cited by 8 | PDF Full-text (1294 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
This study was designed to investigate the antimicrobial activity of two synthetic antimicrobial peptides from an aquatic organism, tilapia piscidin 3 (TP3) and tilapia piscidin 4 (TP4), in vitro and in a murine sepsis model, as compared with ampicillin, tigecycline, and imipenem. Mice
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This study was designed to investigate the antimicrobial activity of two synthetic antimicrobial peptides from an aquatic organism, tilapia piscidin 3 (TP3) and tilapia piscidin 4 (TP4), in vitro and in a murine sepsis model, as compared with ampicillin, tigecycline, and imipenem. Mice were infected with (NDM-1)-producing K. pneumonia and multi-drug resistant Acinetobacter baumannii, and subsequently treated with TP3, TP4, or antibiotics for different periods of time (up to 168 h). Mouse survival and bacterial colony forming units (CFU) in various organs were measured after each treatment. Toxicity was determined based on observation of behavior and measurement of biochemical parameters. TP3 and TP4 exhibited strong activity against K. pneumonia and A. baumannii in vitro. Administration of TP3 (150 μg/mouse) or TP4 (50 μg/mouse) 30 min after infection with K. pneumonia or A. baumannii significantly increased survival in mice. TP4 was more effective than tigecycline at reducing CFU counts in several organs. TP3 and TP4 were shown to be non-toxic, and did not affect mouse behavior. TP3 and TP4 are able at potentiate anti-Acinetobacter baumannii or anti-Klebsiella pneumonia drug activity, reduce bacterial load, and prevent drug resistance, indicating their potential for use in combating multidrug-resistant bacteria. Full article
(This article belongs to the Special Issue Marine Peptides and Their Mimetics)
Open AccessArticle Xyloketal B Attenuates Atherosclerotic Plaque Formation and Endothelial Dysfunction in Apolipoprotein E Deficient Mice
Mar. Drugs 2015, 13(4), 2306-2326; doi:10.3390/md13042306
Received: 13 February 2015 / Revised: 30 March 2015 / Accepted: 3 April 2015 / Published: 14 April 2015
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Abstract
Our previous studies demonstrated that xyloketal B, a novel marine compound with a unique chemical structure, has strong antioxidant actions and can protect against endothelial injury in different cell types cultured in vitro and model organisms in vivo. The oxidative endothelial dysfunction
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Our previous studies demonstrated that xyloketal B, a novel marine compound with a unique chemical structure, has strong antioxidant actions and can protect against endothelial injury in different cell types cultured in vitro and model organisms in vivo. The oxidative endothelial dysfunction and decrease in nitric oxide (NO) bioavailability are critical for the development of atherosclerotic lesion. We thus examined whether xyloketal B had an influence on the atherosclerotic plaque area in apolipoprotein E-deficient (apoE/−) mice fed a high-fat diet and investigated the underlying mechanisms. We found in our present study that the administration of xyloketal B dose-dependently decreased the atherosclerotic plaque area both in the aortic sinus and throughout the aorta in apoE/− mice fed a high-fat diet. In addition, xyloketal B markedly reduced the levels of vascular oxidative stress, as well as improving the impaired endothelium integrity and NO-dependent aortic vasorelaxation in atherosclerotic mice. Moreover, xyloketal B significantly changed the phosphorylation levels of endothelial nitric oxide synthase (eNOS) and Akt without altering the expression of total eNOS and Akt in cultured human umbilical vein endothelial cells (HUVECs). Here, it increased eNOS phosphorylation at the positive regulatory site of Ser-1177, while inhibiting phosphorylation at the negative regulatory site of Thr-495. Taken together, these findings indicate that xyloketal B has dramatic anti-atherosclerotic effects in vivo, which is partly due to its antioxidant features and/or improvement of endothelial function. Full article
Open AccessArticle New Prenylated Aeruginosin, Microphycin, Anabaenopeptin and Micropeptin Analogues from a Microcystis Bloom Material Collected in Kibbutz Kfar Blum, Israel
Mar. Drugs 2015, 13(4), 2347-2375; doi:10.3390/md13042347
Received: 23 November 2014 / Revised: 16 March 2015 / Accepted: 18 March 2015 / Published: 15 April 2015
Cited by 3 | PDF Full-text (1078 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Thirteen new and eighteen known natural products were isolated from a bloom material of an assembly of various Microcystis spp. collected in November, 2008, from a commercial fishpond near Kibbutz Kfar Blum, the Jordan Valley, Israel. The new natural products included the prenylated
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Thirteen new and eighteen known natural products were isolated from a bloom material of an assembly of various Microcystis spp. collected in November, 2008, from a commercial fishpond near Kibbutz Kfar Blum, the Jordan Valley, Israel. The new natural products included the prenylated aeruginosin KB676 (1), microphycin KB921 (2), anabaenopeptins KB906 (3) and KB899 (4) and micropeptins KB928 (5), KB956 (6), KB970A (7), KB970B (8), KB984 (9), KB970C (10), KB1048 (11), KB992 (12) and KB1046 (13). Their structures were elucidated primarily by interpretation of their 1D and 2D nuclear magnetic resonance spectra and high-resolution mass spectrometry. Marfey’s and chiral-phase high performance liquid chromatography methods were used to determine the absolute configurations of their chiral centers. Aeruginosin KB676 (1) contains the rare (2S,3aS,6S,7aS)-Choi and is the first prenylated aeruginosin derivative described in the literature. Compounds 1 and 511 inhibited trypsin with sub-μM IC50s, while Compounds 1113 inhibited chymotrypsin with sub-μM IC50s. The structures and biological activities of the new natural products and our procedures of dereplication are described. Full article
Open AccessArticle Avarol Induces Apoptosis in Pancreatic Ductal Adenocarcinoma Cells by Activating PERK–eIF2α–CHOP Signaling
Mar. Drugs 2015, 13(4), 2376-2389; doi:10.3390/md13042376
Received: 25 February 2015 / Revised: 28 March 2015 / Accepted: 8 April 2015 / Published: 16 April 2015
Cited by 6 | PDF Full-text (1335 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Avarol is a sesquiterpenoid hydroquinone with potent cytotoxicity. Although resolving endoplasmic reticulum (ER) stress is essential for intracellular homeostasis, erratic or excessive ER stress can lead to apoptosis. Here, we reported that avarol selectively induces cell death in pancreatic ductal adenocarcinomas (PDAC),
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Avarol is a sesquiterpenoid hydroquinone with potent cytotoxicity. Although resolving endoplasmic reticulum (ER) stress is essential for intracellular homeostasis, erratic or excessive ER stress can lead to apoptosis. Here, we reported that avarol selectively induces cell death in pancreatic ductal adenocarcinomas (PDAC), which are difficult to treat owing to the availability of few chemotherapeutic agents. Analyses of the molecular mechanisms of avarol-induced apoptosis indicated upregulation of ER stress marker BiP and ER stress-dependent apoptosis inducer CHOP in PDAC cells but not in normal cells, suggesting that avarol selectively induces ER stress responses. We also showed that avarol activated the PERK–eIF2α pathway but did not affect the IRE1 and ATF6 pathways. Moreover, CHOP downregulation was significantly suppressed by avarol-induced apoptosis. Thus, the PERK–eIF2α–CHOP signaling pathway may be a novel molecular mechanism of avarol-induced apoptosis. The present data indicate that avarol has potential as a chemotherapeutic agent for PDAC and induces apoptosis by activating the PERK–eIF2α pathway. Full article
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Open AccessArticle Dihydroaustrasulfone Alcohol Inhibits PDGF-Induced Proliferation and Migration of Human Aortic Smooth Muscle Cells through Inhibition of the Cell Cycle
Mar. Drugs 2015, 13(4), 2390-2406; doi:10.3390/md13042390
Received: 13 February 2015 / Revised: 27 March 2015 / Accepted: 9 April 2015 / Published: 17 April 2015
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Abstract
Dihydroaustrasulfone alcohol is the synthetic precursor of austrasulfone, which is a marine natural product, isolated from the Taiwanese soft coral Cladiella australis. Dihydroaustrasulfone alcohol has anti-inflammatory, neuroprotective, antitumor and anti-atherogenic properties. Although dihydroaustrasulfone alcohol has been shown to inhibit neointima formation, its
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Dihydroaustrasulfone alcohol is the synthetic precursor of austrasulfone, which is a marine natural product, isolated from the Taiwanese soft coral Cladiella australis. Dihydroaustrasulfone alcohol has anti-inflammatory, neuroprotective, antitumor and anti-atherogenic properties. Although dihydroaustrasulfone alcohol has been shown to inhibit neointima formation, its effect on human vascular smooth muscle cells (VSMCs) has not been elucidated. We examined the effects and the mechanisms of action of dihydroaustrasulfone alcohol on proliferation, migration and phenotypic modulation of human aortic smooth muscle cells (HASMCs). Dihydroaustrasulfone alcohol significantly inhibited proliferation, DNA synthesis and migration of HASMCs, without inducing cell death. Dihydroaustrasulfone alcohol also inhibited platelet-derived growth factor (PDGF)-induced expression of cyclin-dependent kinases (CDK) 2, CDK4, cyclin D1 and cyclin E. In addition, dihydroaustrasulfone alcohol inhibited PDGF-induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), whereas it had no effect on the phosphorylation of phosphatidylinositol 3-kinase (PI3K)/(Akt). Moreover, treatment with PD98059, a highly selective ERK inhibitor, blocked PDGF-induced upregulation of cyclin D1 and cyclin E and downregulation of p27kip1. Furthermore, dihydroaustrasulfone alcohol also inhibits VSMC synthetic phenotype formation induced by PDGF. For in vivo studies, dihydroaustrasulfone alcohol decreased smooth muscle cell proliferation in a rat model of restenosis induced by balloon injury. Immunohistochemical staining showed that dihydroaustrasulfone alcohol noticeably decreased the expression of proliferating cell nuclear antigen (PCNA) and altered VSMC phenotype from a synthetic to contractile state. Our findings provide important insights into the mechanisms underlying the vasoprotective actions of dihydroaustrasulfone alcohol and suggest that it may be a useful therapeutic agent for the treatment of vascular occlusive disease. Full article
Open AccessArticle Synthesis and Bioactivity of Luffarin I
Mar. Drugs 2015, 13(4), 2407-2423; doi:10.3390/md13042407
Received: 19 February 2015 / Revised: 20 March 2015 / Accepted: 7 April 2015 / Published: 20 April 2015
Cited by 6 | PDF Full-text (660 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The first synthesis of Luffarin I, sesterterpenolide isolated from sponge Luffariella geometrica, has been accomplished from commercially available sclareol. The key strategy involved in this synthesis is the diastereoselective reduction of an intermediate ketone. Luffarin I against human solid tumor cell lines
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The first synthesis of Luffarin I, sesterterpenolide isolated from sponge Luffariella geometrica, has been accomplished from commercially available sclareol. The key strategy involved in this synthesis is the diastereoselective reduction of an intermediate ketone. Luffarin I against human solid tumor cell lines showed antiproliferative activities (GI50) in the range 12–17 μM. Full article
(This article belongs to the Special Issue Marine Secondary Metabolites)
Open AccessArticle Chitin-Lignin Material as a Novel Matrix for Enzyme Immobilization
Mar. Drugs 2015, 13(4), 2424-2446; doi:10.3390/md13042424
Received: 19 February 2015 / Revised: 23 March 2015 / Accepted: 27 March 2015 / Published: 20 April 2015
Cited by 18 | PDF Full-text (894 KB) | HTML Full-text | XML Full-text
Abstract
Innovative materials were made via the combination of chitin and lignin, and the immobilization of lipase from Aspergillus niger. Analysis by techniques including FTIR, XPS and 13C CP MAS NMR confirmed the effective immobilization of the enzyme on the surface of
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Innovative materials were made via the combination of chitin and lignin, and the immobilization of lipase from Aspergillus niger. Analysis by techniques including FTIR, XPS and 13C CP MAS NMR confirmed the effective immobilization of the enzyme on the surface of the composite support. The electrokinetic properties of the resulting systems were also determined. Results obtained from elemental analysis and by the Bradford method enabled the determination of optimum parameters for the immobilization process. Based on the hydrolysis reaction of para-nitrophenyl palmitate, a determination was made of the catalytic activity, thermal and pH stability, and reusability. The systems with immobilized enzymes were found to have a hydrolytic activity of 5.72 mU, and increased thermal and pH stability compared with the native lipase. The products were also shown to retain approximately 80% of their initial catalytic activity, even after 20 reaction cycles. The immobilization process, using a cheap, non-toxic matrix of natural origin, leads to systems with potential applications in wastewater remediation processes and in biosensors. Full article
(This article belongs to the collection Marine Polysaccharides)
Open AccessArticle Seaweed Polysaccharides (Laminarin and Fucoidan) as Functional Ingredients in Pork Meat: An Evaluation of Anti-Oxidative Potential, Thermal Stability and Bioaccessibility
Mar. Drugs 2015, 13(4), 2447-2464; doi:10.3390/md13042447
Received: 5 February 2015 / Revised: 28 March 2015 / Accepted: 30 March 2015 / Published: 20 April 2015
Cited by 4 | PDF Full-text (440 KB) | HTML Full-text | XML Full-text
Abstract
The anti-oxidative potential of laminarin (L), fucoidan (F) and an L/F seaweed extract was measured using the DPPH free radical scavenging assay, in 25% pork (longissimus thoracis et lumborum (LTL)) homogenates (TBARS) (3 and 6 mg/mL) and in horse heart oxymyoglobin (OxyMb)
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The anti-oxidative potential of laminarin (L), fucoidan (F) and an L/F seaweed extract was measured using the DPPH free radical scavenging assay, in 25% pork (longissimus thoracis et lumborum (LTL)) homogenates (TBARS) (3 and 6 mg/mL) and in horse heart oxymyoglobin (OxyMb) (0.1 and 1 mg/mL). The DPPH activity of fresh and cooked minced LTL containing L (100 mg/g; L100), F100 and L/F100,300, and bioaccessibility post in vitro digestion (L/F300), was assessed. Theoretical cellular uptake of antioxidant compounds was measured in a transwell Caco-2 cell model. Laminarin displayed no activity and fucoidan reduced lipid oxidation but catalysed OxyMb oxidation. Fucoidan activity was lowered by cooking while the L/F extract displayed moderate thermal stability. A decrease in DPPH antioxidant activity of 44.15% and 36.63%, after 4 and 20 h respectively, indicated theoretical uptake of L/F antioxidant compounds. Results highlight the potential use of seaweed extracts as functional ingredients in pork. Full article
(This article belongs to the collection Marine Polysaccharides)
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Open AccessArticle Activation of the Silent Secondary Metabolite Production by Introducing Neomycin-Resistance in a Marine-Derived Penicillium purpurogenum G59
Mar. Drugs 2015, 13(4), 2465-2487; doi:10.3390/md13042465
Received: 28 January 2015 / Revised: 31 March 2015 / Accepted: 8 April 2015 / Published: 22 April 2015
Cited by 9 | PDF Full-text (1261 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Introduction of neomycin-resistance into a marine-derived, wild-type Penicillium purpurogenum G59 resulted in activation of silent biosynthetic pathways for the secondary metabolite production. Upon treatment of G59 spores with neomycin and dimethyl sulfoxide (DMSO), a total of 56 mutants were obtained by single colony
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Introduction of neomycin-resistance into a marine-derived, wild-type Penicillium purpurogenum G59 resulted in activation of silent biosynthetic pathways for the secondary metabolite production. Upon treatment of G59 spores with neomycin and dimethyl sulfoxide (DMSO), a total of 56 mutants were obtained by single colony isolation. The acquired resistance of mutants to neomycin was testified by the resistance test. In contrast to the G59 strain, the EtOAc extracts of 28 mutants inhibited the human cancer K562 cells, indicating that the 28 mutants have acquired the capability to produce bioactive metabolites. HPLC-photodiode array detector (PDAD)-UV and HPLC-electron spray ionization (ESI)-MS analyses further indicated that diverse secondary metabolites have been newly produced in the bioactive mutant extracts. Followed isolation and characterization demonstrated that five bioactive secondary metabolites, curvularin (1), citrinin (2), penicitrinone A (3), erythro-23-O-methylneocyclocitrinol (4) and 22E-7α-methoxy-5α, 6α-epoxyergosta-8(14),22-dien-3β-ol (5), were newly produced by a mutant, 4-30, compared to the G59 strain. All 15 were also not yet found in the secondary metabolites of other wild type P. purpurogenum strains. Compounds 15 inhibited human cancer K562, HL-60, HeLa and BGC-823 cells to varying extents. Both present bioassays and chemical investigations demonstrated that the introduction of neomycin-resistance into the marine-derived fungal G59 strain could activate silent secondary metabolite production. The present work not only extended the previous DMSO-mediated method for introducing drug-resistance in fungi both in DMSO concentrations and antibiotics, but also additionally exemplified effectiveness of this method for activating silent fungal secondary metabolites. This method could be applied to other fungal isolates to elicit their metabolic potentials to investigate secondary metabolites from silent biosynthetic pathways. Full article
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Open AccessArticle Synthesis and in Vitro Antiproliferative Evaluation of Some B-norcholesteryl Benzimidazole and Benzothiazole Derivatives
Mar. Drugs 2015, 13(4), 2488-2504; doi:10.3390/md13042488
Received: 29 January 2015 / Revised: 8 April 2015 / Accepted: 10 April 2015 / Published: 22 April 2015
Cited by 8 | PDF Full-text (937 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Taking orostanal (a compound from a Japanese marine sponge, Stelletta hiwasaensis) as a lead compound, some novel B-norcholesteryl benzimidazole and benzothiazole derivatives were synthesized. The antiproliferative activity of the compounds against human cervical carcinoma (HeLa), human lung carcinoma (A549), human liver carcinoma
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Taking orostanal (a compound from a Japanese marine sponge, Stelletta hiwasaensis) as a lead compound, some novel B-norcholesteryl benzimidazole and benzothiazole derivatives were synthesized. The antiproliferative activity of the compounds against human cervical carcinoma (HeLa), human lung carcinoma (A549), human liver carcinoma cells (HEPG2) and normal kidney epithelial cells (HEK293T) was assayed. The results revealed that the benzimidazole group was a better substituent than benzothiazole group for increasing the antiproliferative activity of compounds. 2-(3β′-Acetoxy-5β′-hydroxy-6′-B-norcholesteryl)benzimidazole (9b) with the structure of 6-benzimidazole displays the best antiproliferative activity to the cancer cells in all compounds, but is almost inactive to normal kidney epithelial cells (HEK293T). The assay of compound 9b to cancer cell apoptosis by flow cytometry showed that the compound was able to effectively induce cancer cell apoptosis. The research provided a theoretical reference for the exploration of new anti-cancer agents and may be useful for the design of novel chemotherapeutic drugs. Full article
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Open AccessArticle Xyloketal B Suppresses Glioblastoma Cell Proliferation and Migration in Vitro through Inhibiting TRPM7-Regulated PI3K/Akt and MEK/ERK Signaling Pathways
Mar. Drugs 2015, 13(4), 2505-2525; doi:10.3390/md13042505
Received: 30 January 2015 / Revised: 3 April 2015 / Accepted: 8 April 2015 / Published: 22 April 2015
Cited by 10 | PDF Full-text (1337 KB) | HTML Full-text | XML Full-text
Abstract
Glioblastoma, the most common and aggressive type of brain tumors, has devastatingly proliferative and invasive characteristics. The need for finding a novel and specific drug target is urgent as the current approaches have limited therapeutic effects in treating glioblastoma. Xyloketal B is a
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Glioblastoma, the most common and aggressive type of brain tumors, has devastatingly proliferative and invasive characteristics. The need for finding a novel and specific drug target is urgent as the current approaches have limited therapeutic effects in treating glioblastoma. Xyloketal B is a marine compound obtained from mangrove fungus Xylaria sp. (No. 2508) from the South China Sea, and has displayed antioxidant activity and protective effects on endothelial and neuronal oxidative injuries. In this study, we used a glioblastoma U251 cell line to (1) explore the effects of xyloketal B on cell viability, proliferation, and migration; and (2) investigate the underlying molecular mechanisms and signaling pathways. MTT assay, colony formation, wound healing, western blot, and patch clamp techniques were employed. We found that xyloketal B reduced cell viability, proliferation, and migration of U251 cells. In addition, xyloketal B decreased p-Akt and p-ERK1/2 protein expressions. Furthermore, xyloketal B blocked TRPM7 currents in HEK-293 cells overexpressing TRPM7. These effects were confirmed by using a TRPM7 inhibitor, carvacrol, in a parallel experiment. Our findings indicate that TRPM7-regulated PI3K/Akt and MEK/ERK signaling is involved in anti-proliferation and migration effects of xyloketal B on U251 cells, providing in vitro evidence for the marine compound xyloketal B to be a potential drug for treating glioblastoma. Full article
(This article belongs to the collection Marine Compounds and Cancer) Printed Edition available
Open AccessArticle New Polyphenols from a Deep Sea Spiromastix sp. Fungus, and Their Antibacterial Activities
Mar. Drugs 2015, 13(4), 2526-2540; doi:10.3390/md13042526
Received: 11 February 2015 / Revised: 7 April 2015 / Accepted: 13 April 2015 / Published: 22 April 2015
Cited by 8 | PDF Full-text (655 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Eleven new polyphenols namely spiromastols A–K (111) were isolated from the fermentation broth of a deep sea-derived fungus Spiromastix sp. MCCC 3A00308. Their structures were determined by extensive NMR data and mass spectroscopic analysis in association with chemical conversion.
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Eleven new polyphenols namely spiromastols A–K (111) were isolated from the fermentation broth of a deep sea-derived fungus Spiromastix sp. MCCC 3A00308. Their structures were determined by extensive NMR data and mass spectroscopic analysis in association with chemical conversion. The structures are classified as diphenyl ethers, diphenyl esters and isocoumarin derivatives, while the n-propyl group in the analogues is rarely found in natural products. Compounds 13 exhibited potent inhibitory effects against a panel of bacterial strains, including Xanthomanes vesicatoria, Pseudomonas lachrymans, Agrobacterium tumefaciens, Ralstonia solanacearum, Bacillus thuringensis, Staphylococcus aureus and Bacillus subtilis, with minimal inhibitory concentration (MIC) values ranging from 0.25 to 4 µg/mL. The structure-activity relationships are discussed, while the polychlorinated analogues 13 are assumed to be a promising structural model for further development as antibacterial agents. Full article
(This article belongs to the Special Issue Bioactive Compounds from Marine Fungi)
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Open AccessArticle UPLC-MSE Profiling of Phytoplankton Metabolites: Application to the Identification of Pigments and Structural Analysis of Metabolites in Porphyridium purpureum
Mar. Drugs 2015, 13(4), 2541-2558; doi:10.3390/md13042541
Received: 11 February 2015 / Revised: 1 April 2015 / Accepted: 8 April 2015 / Published: 22 April 2015
Cited by 5 | PDF Full-text (809 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A fast and high-resolution UPLC-MSE analysis was used to identify phytoplankton pigments in an ethanol extract of Porphyridium purpureum (Pp) devoid of phycobiliproteins. In a first step, 22 standard pigments were analyzed by UPLC-MSE to build a database including
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A fast and high-resolution UPLC-MSE analysis was used to identify phytoplankton pigments in an ethanol extract of Porphyridium purpureum (Pp) devoid of phycobiliproteins. In a first step, 22 standard pigments were analyzed by UPLC-MSE to build a database including retention time and accurate masses of parent and fragment ions. Using this database, seven pigments or derivatives previously reported in Pp were unequivocally identified: β,β-carotene, chlorophyll a, zeaxanthin, chlorophyllide a, pheophorbide a, pheophytin a, and cryptoxanthin. Minor amounts of Divinyl chlorophyll a, a chemotaxonomic pigment marker for prochlorophytes, were also unequivocally identified using the database. Additional analysis of ionization and fragmentation patterns indicated the presence of ions that could correspond to hydroxylated derivatives of chlorophyll a and pheophytin a, produced during the ethanolic extraction, as well as previously described galactosyldiacylglycerols, the thylakoid coenzyme plastoquinone, and gracilamide B, a molecule previously reported in the red seaweed Gracillaria asiatica. These data point to UPLC-MSE as an efficient technique to identify phytoplankton pigments for which standards are available, and demonstrate its major interest as a complementary method for the structural elucidation of ionizable marine molecules. Full article

Review

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Open AccessReview Cadmium-Containing Carbonic Anhydrase CDCA1 in Marine Diatom Thalassiosira weissflogii
Mar. Drugs 2015, 13(4), 1688-1697; doi:10.3390/md13041688
Received: 20 January 2015 / Revised: 12 March 2015 / Accepted: 17 March 2015 / Published: 25 March 2015
Cited by 9 | PDF Full-text (796 KB) | HTML Full-text | XML Full-text
Abstract
The Carbon Concentration Mechanism (CCM) allows phytoplakton species to accumulate the dissolved inorganic carbon (DIC) necessary for an efficient photosynthesis even under carbon dioxide limitation. In this mechanism of primary importance for diatoms, a key role is played by carbonic anhydrase (CA) enzymes
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The Carbon Concentration Mechanism (CCM) allows phytoplakton species to accumulate the dissolved inorganic carbon (DIC) necessary for an efficient photosynthesis even under carbon dioxide limitation. In this mechanism of primary importance for diatoms, a key role is played by carbonic anhydrase (CA) enzymes which catalyze the reversible hydration of CO2, thus taking part in the acquisition of inorganic carbon for photosynthesis. A novel CA, named CDCA1, has been recently discovered in the marine diatom Thalassiosira weissflogii. CDCA1 is a cambialistic enzyme since it naturally uses Cd2+ as catalytic metal ion, but if necessary can spontaneously exchange Cd2+ to Zn2+. Here, the biochemical and structural features of CDCA1 enzyme will be presented together with its putative biotechnological applications for the detection of metal ions in seawaters. Full article
(This article belongs to the Special Issue Metabolites in Diatoms)
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Open AccessReview Stability of Chitosan—A Challenge for Pharmaceutical and Biomedical Applications
Mar. Drugs 2015, 13(4), 1819-1846; doi:10.3390/md13041819
Received: 25 February 2015 / Revised: 19 March 2015 / Accepted: 20 March 2015 / Published: 1 April 2015
Cited by 48 | PDF Full-text (746 KB) | HTML Full-text | XML Full-text
Abstract
Chitosan—one of the natural multifunctional polymers—due to its unique and versatile biological properties is regarded as a useful compound in medical and pharmaceutical technology. Recently, considerable research effort has been made in order to develop safe and efficient chitosan products. However, the problem
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Chitosan—one of the natural multifunctional polymers—due to its unique and versatile biological properties is regarded as a useful compound in medical and pharmaceutical technology. Recently, considerable research effort has been made in order to develop safe and efficient chitosan products. However, the problem of poor stability of chitosan-based systems restricts its practical applicability; thus, it has become a great challenge to establish sufficient shelf-life for chitosan formulations. Improved stability can be assessed by controlling the environmental factors, manipulating processing conditions (e.g., temperature), introducing a proper stabilizing compound, developing chitosan blends with another polymer, or modifying the chitosan structure using chemical or ionic agents. This review covers the influence of internal, environmental, and processing factors on the long-term stability of chitosan products. The aim of this paper is also to highlight the latest developments which enable the physicochemical properties of chitosan-based applications to be preserved upon storage. Full article
(This article belongs to the collection Marine Polysaccharides)
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Open AccessReview Recent Advances in Exopolysaccharides from Paenibacillus spp.: Production, Isolation, Structure, and Bioactivities
Mar. Drugs 2015, 13(4), 1847-1863; doi:10.3390/md13041847
Received: 24 February 2015 / Revised: 23 March 2015 / Accepted: 25 March 2015 / Published: 1 April 2015
Cited by 19 | PDF Full-text (425 KB) | HTML Full-text | XML Full-text
Abstract
This review provides a comprehensive summary of the most recent developments of various aspects (i.e., production, purification, structure, and bioactivity) of the exopolysaccharides (EPSs) from Paenibacillus spp. For the production, in particular, squid pen waste was first utilized successfully to produce
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This review provides a comprehensive summary of the most recent developments of various aspects (i.e., production, purification, structure, and bioactivity) of the exopolysaccharides (EPSs) from Paenibacillus spp. For the production, in particular, squid pen waste was first utilized successfully to produce a high yield of inexpensive EPSs from Paenibacillus sp. TKU023 and P. macerans TKU029. In addition, this technology for EPS production is prevailing because it is more environmentally friendly. The Paenibacillus spp. EPSs reported from various references constitute a structurally diverse class of biological macromolecules with different applications in the broad fields of pharmacy, cosmetics and bioremediation. The EPS produced by P. macerans TKU029 can increase in vivo skin hydration and may be a new source of natural moisturizers with potential value in cosmetics. However, the relationships between the structures and activities of these EPSs in many studies are not well established. The contents and data in this review will serve as useful references for further investigation, production, structure and application of Paenibacillus spp. EPSs in various fields. Full article
(This article belongs to the collection Marine Polysaccharides)
Open AccessReview Marine Extremophiles: A Source of Hydrolases for Biotechnological Applications
Mar. Drugs 2015, 13(4), 1925-1965; doi:10.3390/md13041925
Received: 1 December 2014 / Revised: 22 March 2015 / Accepted: 25 March 2015 / Published: 3 April 2015
Cited by 38 | PDF Full-text (1197 KB) | HTML Full-text | XML Full-text
Abstract
The marine environment covers almost three quarters of the planet and is where evolution took its first steps. Extremophile microorganisms are found in several extreme marine environments, such as hydrothermal vents, hot springs, salty lakes and deep-sea floors. The ability of these microorganisms
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The marine environment covers almost three quarters of the planet and is where evolution took its first steps. Extremophile microorganisms are found in several extreme marine environments, such as hydrothermal vents, hot springs, salty lakes and deep-sea floors. The ability of these microorganisms to support extremes of temperature, salinity and pressure demonstrates their great potential for biotechnological processes. Hydrolases including amylases, cellulases, peptidases and lipases from hyperthermophiles, psychrophiles, halophiles and piezophiles have been investigated for these reasons. Extremozymes are adapted to work in harsh physical-chemical conditions and their use in various industrial applications such as the biofuel, pharmaceutical, fine chemicals and food industries has increased. The understanding of the specific factors that confer the ability to withstand extreme habitats on such enzymes has become a priority for their biotechnological use. The most studied marine extremophiles are prokaryotes and in this review, we present the most studied archaea and bacteria extremophiles and their hydrolases, and discuss their use for industrial applications. Full article
(This article belongs to the Special Issue Bioactive Compounds from Marine Microbes)
Open AccessReview Bioactive Terpenes from Marine-Derived Fungi
Mar. Drugs 2015, 13(4), 1966-1992; doi:10.3390/md13041966
Received: 4 December 2014 / Revised: 25 February 2015 / Accepted: 14 March 2015 / Published: 3 April 2015
Cited by 6 | PDF Full-text (2174 KB) | HTML Full-text | XML Full-text
Abstract
Marine-derived fungi continue to be a prolific source of secondary metabolites showing diverse bioactivities. Terpenoids from marine-derived fungi exhibit wide structural diversity including numerous compounds with pronounced biological activities. In this review, we survey the last five years’ reports on terpenoidal metabolites from
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Marine-derived fungi continue to be a prolific source of secondary metabolites showing diverse bioactivities. Terpenoids from marine-derived fungi exhibit wide structural diversity including numerous compounds with pronounced biological activities. In this review, we survey the last five years’ reports on terpenoidal metabolites from marine-derived fungi with particular attention on those showing marked biological activities. Full article
(This article belongs to the Special Issue Terpenoids of Marine Origin)
Open AccessReview Marine Natural Products as Breast Cancer Resistance Protein Inhibitors
Mar. Drugs 2015, 13(4), 2010-2029; doi:10.3390/md13042010
Received: 20 February 2015 / Revised: 19 March 2015 / Accepted: 24 March 2015 / Published: 3 April 2015
Cited by 15 | PDF Full-text (949 KB) | HTML Full-text | XML Full-text
Abstract
Breast cancer resistance protein (BCRP) is a protein belonging to the ATP-binding cassette (ABC) transporter superfamily that has clinical relevance due to its multi-drug resistance properties in cancer. BCRP can be associated with clinical cancer drug resistance, in particular acute myelogenous or acute
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Breast cancer resistance protein (BCRP) is a protein belonging to the ATP-binding cassette (ABC) transporter superfamily that has clinical relevance due to its multi-drug resistance properties in cancer. BCRP can be associated with clinical cancer drug resistance, in particular acute myelogenous or acute lymphocytic leukemias. The overexpression of BCRP contributes to the resistance of several chemotherapeutic drugs, such as topotecan, methotrexate, mitoxantrone, doxorubicin and daunorubicin. The Food and Drugs Administration has already recognized that BCRP is clinically one of the most important drug transporters, mainly because it leads to a reduction of clinical efficacy of various anticancer drugs through its ATP-dependent drug efflux pump function as well as its apparent participation in drug resistance. This review article aims to summarize the different research findings on marine natural products with BCRP inhibiting activity. In this sense, the potential modulation of physiological targets of BCRP by natural or synthetic compounds offers a great possibility for the discovery of new drugs and valuable research tools to recognize the function of the complex ABC-transporters. Full article
Open AccessReview The Potential of Chitosan and Its Derivatives in Prevention and Treatment of Age-Related Diseases
Mar. Drugs 2015, 13(4), 2158-2182; doi:10.3390/md13042158
Received: 19 February 2015 / Revised: 23 March 2015 / Accepted: 26 March 2015 / Published: 13 April 2015
Cited by 21 | PDF Full-text (579 KB) | HTML Full-text | XML Full-text
Abstract
Age-related, diet-related and protein conformational diseases, such as atherosclerosis, diabetes mellitus, cancer, hypercholesterolemia, cardiovascular and neurodegenerative diseases are common in the elderly population. The potential of chitosan, chitooligosaccharides and their derivatives in prevention and treatment of age-related dysfunctions is reviewed and discussed in
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Age-related, diet-related and protein conformational diseases, such as atherosclerosis, diabetes mellitus, cancer, hypercholesterolemia, cardiovascular and neurodegenerative diseases are common in the elderly population. The potential of chitosan, chitooligosaccharides and their derivatives in prevention and treatment of age-related dysfunctions is reviewed and discussed in this paper. The influence of oxidative stress, low density lipoprotein oxidation, increase of tissue stiffness, protein conformational changes, aging-associated chronic inflammation and their pathobiological significance have been considered. The chitosan-based functional food also has been reviewed. Full article
(This article belongs to the collection Marine Polysaccharides)
Open AccessReview Anti-Obesity Activity of the Marine Carotenoid Fucoxanthin
Mar. Drugs 2015, 13(4), 2196-2214; doi:10.3390/md13042196
Received: 23 December 2014 / Revised: 20 March 2015 / Accepted: 1 April 2015 / Published: 13 April 2015
Cited by 35 | PDF Full-text (599 KB) | HTML Full-text | XML Full-text
Abstract
Nowadays the global tendency towards physical activity reduction and an augmented dietary intake of fats, sugars and calories is leading to a growing propagation of overweight, obesity and lifestyle-related diseases, such diabetes, hypertension, dyslipidemia and metabolic syndrome. In particular, obesity, characterized as a
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Nowadays the global tendency towards physical activity reduction and an augmented dietary intake of fats, sugars and calories is leading to a growing propagation of overweight, obesity and lifestyle-related diseases, such diabetes, hypertension, dyslipidemia and metabolic syndrome. In particular, obesity, characterized as a state of low-level inflammation, is a powerful determinant both in the development of insulin resistance and in the progression to type 2 diabetes. A few molecular targets offer hope for anti-obesity therapeutics. One of the keys to success could be the induction of uncoupling protein 1 (UCP1) in abdominal white adipose tissue (WAT) and the regulation of cytokine secretions from both abdominal adipose cells and macrophage cells infiltrated into adipose tissue. Anti-obesity effects of fucoxanthin, a characteristic carotenoid, exactly belonging to xanthophylls, have been reported. Nutrigenomic studies reveal that fucoxanthin induces UCP1 in abdominal WAT mitochondria, leading to the oxidation of fatty acids and heat production in WAT. Fucoxanthin improves insulin resistance and decreases blood glucose levels through the regulation of cytokine secretions from WAT. The key structure of anti-obesity effect is suggested to be the carotenoid end of the polyene chromophore, which contains an allenic bond and two hydroxyl groups. Fucoxanthin, which can be isolated from edible brown seaweeds, recently displayed its many physiological functions and biological properties. We reviewed recent studies and this article aims to explain essential background of fucoxanthin, focusing on its promising potential anti-obesity effects. In this respect, fucoxanthin can be developed into promising marine drugs and nutritional products, in order to become a helpful functional food. Full article
(This article belongs to the Special Issue Marine Functional Food)
Open AccessReview Fucoidan and Cancer: A Multifunctional Molecule with Anti-Tumor Potential
Mar. Drugs 2015, 13(4), 2327-2346; doi:10.3390/md13042327
Received: 24 February 2015 / Revised: 25 March 2015 / Accepted: 3 April 2015 / Published: 14 April 2015
Cited by 36 | PDF Full-text (1022 KB) | HTML Full-text | XML Full-text
Abstract
There is a wide variety of cancer types yet, all share some common cellular and molecular behaviors. Most of the chemotherapeutic agents used in cancer treatment are designed to target common deregulated mechanisms within cancer cells. Many healthy tissues are also affected by
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There is a wide variety of cancer types yet, all share some common cellular and molecular behaviors. Most of the chemotherapeutic agents used in cancer treatment are designed to target common deregulated mechanisms within cancer cells. Many healthy tissues are also affected by the cytotoxic effects of these chemical agents. Fucoidan, a natural component of brown seaweed, has anti-cancer activity against various cancer types by targeting key apoptotic molecules. It also has beneficial effects as it can protect against toxicity associated with chemotherapeutic agents and radiation. Thus the synergistic effect of fucoidan with current anti-cancer agents is of considerable interest. This review discusses the mechanisms by which fucoidan retards tumor development, eradicates tumor cells and synergizes with anti-cancer chemotherapeutic agents. Challenges to the development of fucoidan as an anti-cancer agent will also be discussed. Full article
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