Next Issue
Previous Issue

E-Mail Alert

Add your e-mail address to receive forthcoming issues of this journal:

Journal Browser

Journal Browser

Table of Contents

Mar. Drugs, Volume 12, Issue 11 (November 2014), Pages 5328-5718

  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Readerexternal link to open them.
View options order results:
result details:
Displaying articles 1-19
Export citation of selected articles as:

Research

Jump to: Review

Open AccessArticle Triphlorethol-A from Ecklonia cava Up-Regulates the Oxidant Sensitive 8-Oxoguanine DNA Glycosylase 1
Mar. Drugs 2014, 12(11), 5357-5371; doi:10.3390/md12115357
Received: 10 July 2014 / Revised: 2 October 2014 / Accepted: 14 October 2014 / Published: 28 October 2014
Cited by 3 | PDF Full-text (507 KB) | HTML Full-text | XML Full-text
Abstract
This study investigated the protective mechanisms of triphlorethol-A, isolated from Ecklonia cava, against oxidative stress-induced DNA base damage, especially 8-oxoguanine (8-oxoG), in Chinese hamster lung fibroblast V79-4 cells. 8-Oxoguanine DNA glycosylase-1 (OGG1) plays an important role in the removal of 8-oxoG
[...] Read more.
This study investigated the protective mechanisms of triphlorethol-A, isolated from Ecklonia cava, against oxidative stress-induced DNA base damage, especially 8-oxoguanine (8-oxoG), in Chinese hamster lung fibroblast V79-4 cells. 8-Oxoguanine DNA glycosylase-1 (OGG1) plays an important role in the removal of 8-oxoG during the cellular response to DNA base damage. Triphlorethol-A significantly decreased the levels of 8-oxoG induced by H2O2, and this correlated with increases in OGG1 mRNA and OGG1 protein levels. Furthermore, siOGG1-transfected cell attenuated the protective effect of triphlorethol-A against H2O2 treatment. Nuclear factor erythroid 2–related factor 2 (Nrf2) is a transcription factor for OGG1, and Nrf2 combines with small Maf proteins in the nucleus to bind to antioxidant response elements (ARE) in the upstream promoter region of the OGG1 gene. Triphlorethol-A restored the expression of nuclear Nrf2, small Maf protein, and the Nrf2-Maf complex, all of which were reduced by oxidative stress. Furthermore, triphlorethol-A increased Nrf2 binding to ARE sequences and the resulting OGG1 promoter activity, both of which were also reduced by oxidative stress. The levels of the phosphorylated forms of Akt kinase, downstream of phosphatidylinositol 3-kinase (PI3K), and Erk, which are regulators of OGG1, were sharply decreased by oxidative stress, but these decreases were prevented by triphlorethol-A. Specific PI3K, Akt, and Erk inhibitors abolished the cytoprotective effects of triphlorethol-A, suggesting that OGG1 induction by triphlorethol-A involves the PI3K/Akt and Erk pathways. Taken together, these data indicate that by activating the DNA repair system, triphlorethol-A exerts protective effects against DNA base damage induced by oxidative stress. Full article
Open AccessArticle High Levels of Structural Diversity Observed in Microcystins from Microcystis CAWBG11 and Characterization of Six New Microcystin Congeners
Mar. Drugs 2014, 12(11), 5372-5395; doi:10.3390/md12115372
Received: 10 September 2014 / Revised: 21 October 2014 / Accepted: 23 October 2014 / Published: 13 November 2014
Cited by 52 | PDF Full-text (983 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Microcystins (MCs) are cyclic peptides produced by cyanobacteria, which can be harmful to humans and animals when ingested. Differences in the coding of the non‑ribosomal peptide synthetase/polyketide synthase enzyme complex responsible for microcystin production have resulted in more than 100 microcystin variants being
[...] Read more.
Microcystins (MCs) are cyclic peptides produced by cyanobacteria, which can be harmful to humans and animals when ingested. Differences in the coding of the non‑ribosomal peptide synthetase/polyketide synthase enzyme complex responsible for microcystin production have resulted in more than 100 microcystin variants being reported to date. The microcystin diversity of Microcystis CAWBG11 was investigated using matrix-assisted laser desorption/ionization-time of flight mass spectrometry and liquid chromatography-mass spectrometry. This revealed that CAWBG11 simultaneously produced 21 known microcystins and six new congeners: [Asp3] MC-RA, [Asp3] MC-RAba, [Asp3] MC-FA, [Asp3] MC-WA, MC-FAba and MC-FL. The new congeners were putatively characterized by tandem mass spectrometry and chemical derivatization. A survey of the microcystin congeners produced by 49 cyanobacterial strains documented in scientific literature showed that cyanobacteria generally produce four microcystin congeners, but strains which produce up to 47 microcystin congeners have been reported. Microcystis CAWBG11 (which produces at least 27 congeners) was positioned in the top ten percentile of the strains surveyed, and showed fluidity of the amino acids incorporated into both position two and position four. Full article
Figures

Open AccessArticle Resolvin D1, a Metabolite of Omega-3 Polyunsaturated Fatty Acid, Decreases Post-Myocardial Infarct Depression
Mar. Drugs 2014, 12(11), 5396-5407; doi:10.3390/md12115396
Received: 24 September 2014 / Revised: 30 October 2014 / Accepted: 4 November 2014 / Published: 13 November 2014
Cited by 10 | PDF Full-text (571 KB) | HTML Full-text | XML Full-text
Abstract
We hypothesized that inflammation induced by myocardial ischemia plays a central role in depression-like behavior after myocardial infarction (MI). Several experimental approaches that reduce inflammation also result in attenuation of depressive symptoms. We have demonstrated that Resolvin D1 (RvD1), a metabolite of omega-3
[...] Read more.
We hypothesized that inflammation induced by myocardial ischemia plays a central role in depression-like behavior after myocardial infarction (MI). Several experimental approaches that reduce inflammation also result in attenuation of depressive symptoms. We have demonstrated that Resolvin D1 (RvD1), a metabolite of omega-3 polyunsaturated fatty acids (PUFA) derived from docosahexaenoic acid, diminishes infarct size and neutrophil accumulation in the ischemic myocardium. The aim of this study is to determine if a single RvD1 injection could alleviate depressive symptoms in a rat model of MI. MI was induced in rats by occlusion of the left anterior descending coronary artery for 40 min. Five minutes before ischemia or after reperfusion, 0.1 μg of RvD1 or vehicle was injected in the left ventricle cavity. Fourteen days after MI, behavioral tests (forced swim test and socialization) were conducted to evaluate depression-like symptoms. RvD1 reduced infarct size in the treated vs. the vehicle group. Animals receiving RvD1 also showed better performance in the forced swim and social interaction tests vs. vehicle controls. These results indicate that a single RvD1 dose, given 5 min before occlusion or 5 min after the onset of reperfusion, decreases infarct size and attenuates depression-like symptoms. Full article
(This article belongs to the Special Issue Marine Functional Food Products - Cardiovascular Diseases)
Figures

Open AccessArticle Polyketide Synthases in the Microbiome of the Marine Sponge Plakortis halichondrioides: A Metagenomic Update
Mar. Drugs 2014, 12(11), 5425-5440; doi:10.3390/md12115425
Received: 9 September 2014 / Revised: 4 November 2014 / Accepted: 6 November 2014 / Published: 14 November 2014
Cited by 17 | PDF Full-text (1646 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Sponge-associated microorganisms are able to assemble the complex machinery for the production of secondary metabolites such as polyketides, the most important class of marine natural products from a drug discovery perspective. A comprehensive overview of polyketide biosynthetic genes of the sponge Plakortis halichondrioides
[...] Read more.
Sponge-associated microorganisms are able to assemble the complex machinery for the production of secondary metabolites such as polyketides, the most important class of marine natural products from a drug discovery perspective. A comprehensive overview of polyketide biosynthetic genes of the sponge Plakortis halichondrioides and its symbionts was obtained in the present study by massively parallel 454 pyrosequencing of complex and heterogeneous PCR (Polymerase Chain Reaction) products amplified from the metagenomic DNA of a specimen of P. halichondrioides collected in the Caribbean Sea. This was accompanied by a survey of the bacterial diversity within the sponge. In line with previous studies, sequences belonging to supA and swfA, two widespread sponge-specific groups of polyketide synthase (PKS) genes were dominant. While they have been previously reported as belonging to Poribacteria (a novel bacterial phylum found exclusively in sponges), re-examination of current genomic sequencing data showed supA and swfA not to be present in the poribacterial genome. Several non-supA, non-swfA type-I PKS fragments were also identified. A significant portion of these fragments resembled type-I PKSs from protists, suggesting that bacteria may not be the only source of polyketides from P. halichondrioides, and that protistan PKSs should receive further investigation as a source of novel polyketides. Full article
(This article belongs to the Special Issue Marine Secondary Metabolites)
Figures

Open AccessArticle Beta-N-Methylamino-l-Alanine: LC-MS/MS Optimization, Screening of Cyanobacterial Strains and Occurrence in Shellfish from Thau, a French Mediterranean Lagoon
Mar. Drugs 2014, 12(11), 5441-5467; doi:10.3390/md12115441
Received: 4 August 2014 / Revised: 28 October 2014 / Accepted: 6 November 2014 / Published: 17 November 2014
Cited by 18 | PDF Full-text (1154 KB) | HTML Full-text | XML Full-text
Abstract
β-N-methylamino-l-alanine (BMAA) is a neurotoxic non-protein amino acid suggested to be involved in neurodegenerative diseases. It was reported to be produced by cyanobacteria, but also found in edible aquatic organisms, thus raising concern of a widespread human exposure. However, the chemical
[...] Read more.
β-N-methylamino-l-alanine (BMAA) is a neurotoxic non-protein amino acid suggested to be involved in neurodegenerative diseases. It was reported to be produced by cyanobacteria, but also found in edible aquatic organisms, thus raising concern of a widespread human exposure. However, the chemical analysis of BMAA and its isomers are controversial, mainly due to the lack of selectivity of the analytical methods. Using factorial design, we have optimized the chromatographic separation of underivatized analogues by a hydrophilic interaction chromatography coupled to tandem mass spectrometry (HILIC-MS/MS) method. A combination of an effective solid phase extraction (SPE) clean-up, appropriate chromatographic resolution and the use of specific mass spectral transitions allowed for the development of a highly selective and sensitive analytical procedure to identify and quantify BMAA and its isomers (in both free and total form) in cyanobacteria and mollusk matrices (LOQ of 0.225 and 0.15 µg/g dry weight, respectively). Ten species of cyanobacteria (six are reported to be BMAA producers) were screened with this method, and neither free nor bound BMAA could be found, while both free and bound DAB were present in almost all samples. Mussels and oysters collected in 2009 in the Thau Lagoon, France, were also screened, and bound BMAA and its two isomers, DAB and AEG, were observed in all samples (from 0.6 to 14.4 µg/g DW), while only several samples contained quantifiable free BMAA. Full article
(This article belongs to the Special Issue Emerging Marine Toxins)
Open AccessArticle Inhibition of Bacterial Quorum Sensing by Extracts from Aquatic Fungi: First Report from Marine Endophytes
Mar. Drugs 2014, 12(11), 5503-5526; doi:10.3390/md12115503
Received: 19 September 2014 / Revised: 7 November 2014 / Accepted: 7 November 2014 / Published: 19 November 2014
Cited by 11 | PDF Full-text (1177 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In our search for quorum-sensing (QS) disrupting molecules, 75 fungal isolates were recovered from reef organisms (endophytes), saline lakes and mangrove rhizosphere. Their QS inhibitory activity was evaluated in Chromobacterium violaceum CVO26. Four strains of endophytic fungi stood out for their potent activity
[...] Read more.
In our search for quorum-sensing (QS) disrupting molecules, 75 fungal isolates were recovered from reef organisms (endophytes), saline lakes and mangrove rhizosphere. Their QS inhibitory activity was evaluated in Chromobacterium violaceum CVO26. Four strains of endophytic fungi stood out for their potent activity at concentrations from 500 to 50 μg mL−1. The molecular characterization, based on the internal transcribed spacer (ITS) region sequences (ITS1, 5.8S and ITS2) between the rRNA of 18S and 28S, identified these strains as belonging to four genera: Sarocladium (LAEE06), Fusarium (LAEE13), Epicoccum (LAEE14), and Khuskia (LAEE21). Interestingly, three came from coral species and two of them came from the same organism, the coral Diploria strigosa. Metabolic profiles obtained by Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS) suggest that a combination of fungal secondary metabolites and fatty acids could be the responsible for the observed activities. The LC-HRMS analysis also revealed the presence of potentially new secondary metabolites. This is, to the best of our knowledge, the first report of QS inhibition by marine endophytic fungi. Full article
(This article belongs to the Special Issue Bioactive Compounds from Marine Fungi)
Open AccessArticle Global and Phylogenetic Distribution of Quorum Sensing Signals, Acyl Homoserine Lactones, in the Family of Vibrionaceae
Mar. Drugs 2014, 12(11), 5527-5546; doi:10.3390/md12115527
Received: 1 September 2014 / Revised: 5 November 2014 / Accepted: 6 November 2014 / Published: 20 November 2014
Cited by 13 | PDF Full-text (1039 KB) | HTML Full-text | XML Full-text | Correction | Supplementary Files
Abstract
Bacterial quorum sensing (QS) and the corresponding signals, acyl homoserine lactones (AHLs), were first described for a luminescent Vibrio species. Since then, detailed knowledge has been gained on the functional level of QS; however, the abundance of AHLs in the family of Vibrionaceae
[...] Read more.
Bacterial quorum sensing (QS) and the corresponding signals, acyl homoserine lactones (AHLs), were first described for a luminescent Vibrio species. Since then, detailed knowledge has been gained on the functional level of QS; however, the abundance of AHLs in the family of Vibrionaceae in the environment has remained unclear. Three hundred and one Vibrionaceae strains were collected on a global research cruise and the prevalence and profile of AHL signals in this global collection were determined. AHLs were detected in 32 of the 301 strains using Agrobacterium tumefaciens and Chromobacterium violaceum reporter strains. Ethyl acetate extracts of the cultures were analysed by ultra-high performance liquid chromatography-high resolution mass spectrometry (MS) with automated tandem MS confirmation for AHLs. N-(3-hydroxy-hexanoyl) (OH-C6) and N-(3-hydroxy-decanoyl) (OH-C10) homoserine lactones were the most common AHLs found in 17 and 12 strains, respectively. Several strains produced a diversity of different AHLs, including N-heptanoyl (C7) HL. AHL-producing Vibrionaceae were found in polar, temperate and tropical waters. The AHL profiles correlated with strain phylogeny based on gene sequence homology, however not with geographical location. In conclusion, a wide range of AHL signals are produced by a number of clades in the Vibrionaceae family and these results will allow future investigations of inter- and intra-species interactions within this cosmopolitan family of marine bacteria. Full article
(This article belongs to the Special Issue Bioactive Compounds from Marine Microbes)
Open AccessArticle Synthesis and Rheological Characterization of Water-Soluble Glycidyltrimethylammonium-Chitosan
Mar. Drugs 2014, 12(11), 5547-5562; doi:10.3390/md12115547
Received: 9 October 2014 / Revised: 5 November 2014 / Accepted: 12 November 2014 / Published: 20 November 2014
Cited by 2 | PDF Full-text (744 KB) | HTML Full-text | XML Full-text
Abstract
In this study, chitosan (CS) grafted by glycidyltrimethylammonium chloride (GTMAC) to form GTMAC-CS was synthesized, chemically identified, and rheologically characterized. The Maxwell Model can be applied to closely simulate the dynamic rheological performance of the chitosan and the GTMAC-CS solutions, revealing a single
[...] Read more.
In this study, chitosan (CS) grafted by glycidyltrimethylammonium chloride (GTMAC) to form GTMAC-CS was synthesized, chemically identified, and rheologically characterized. The Maxwell Model can be applied to closely simulate the dynamic rheological performance of the chitosan and the GTMAC-CS solutions, revealing a single relaxation time pertains to both systems. The crossover point of G′ and Gʺ shifted toward lower frequencies as the CS concentration increased but remained almost constant frequencies as the GTMAC-CS concentration increased, indicating the solubility of GTMAC-CS in water is good enough to diminish influence from the interaction among polymer chains so as to ensure the relaxation time is independent of the concentration. A frequency–concentration superposition master curve of the CS and GTMAC-CS solutions was subsequently proposed and well fitted with the experimental results. Finally, the sol-gel transition of CS is 8.5 weight % (wt %), while that of GTMAC-CS is 20 wt %, reconfirming the excellent water solubility of the latter. Full article
(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan) Printed Edition available
Figures

Open AccessArticle Five New Secondary Metabolites Produced by a Marine-Associated Fungus, Daldinia eschscholzii
Mar. Drugs 2014, 12(11), 5563-5575; doi:10.3390/md12115563
Received: 16 October 2014 / Revised: 12 November 2014 / Accepted: 13 November 2014 / Published: 20 November 2014
Cited by 7 | PDF Full-text (799 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Five new compounds, including a benzopyran ribonic glycoside, daldiniside A (1), two isocoumarin ribonic glycosides, daldinisides B (2) and C (3), and two alkaloids, 1-(3-indolyl)-2R,3-dihydroxypropan-1-one (4) and 3-ethyl-2, 5-pyrazinedipropanoic acid (5),
[...] Read more.
Five new compounds, including a benzopyran ribonic glycoside, daldiniside A (1), two isocoumarin ribonic glycosides, daldinisides B (2) and C (3), and two alkaloids, 1-(3-indolyl)-2R,3-dihydroxypropan-1-one (4) and 3-ethyl-2, 5-pyrazinedipropanoic acid (5), along with five known compounds (610), were isolated from the EtOAc extract of the marine-associated fungus, Daldinia eschscholzii. Their structures were elucidated by extensive physicochemical and spectroscopic properties, besides comparison with literature data. The absolute configurations of compounds 13 were corroborated by chemical transformation, GC analysis and X-ray crystallographic analysis. Meanwhile, the absolute configuration of compound 4 and the planar structure of compound 6 were also determined based on the X-ray diffraction analysis. The cytotoxicity of compounds 110, antifungal and anti-HIV activities of compounds 15 and the in vitro assay for glucose consumption of compounds 13 were done in the anti-diabetic model, whereas none showed obvious activity. Full article
Figures

Open AccessArticle Programmed Cell Death Induced by (−)-8,9-Dehydroneopeltolide in Human Promyelocytic Leukemia HL-60 Cells under Energy Stress Conditions
Mar. Drugs 2014, 12(11), 5576-5589; doi:10.3390/md12115576
Received: 15 October 2014 / Revised: 5 November 2014 / Accepted: 7 November 2014 / Published: 20 November 2014
Cited by 5 | PDF Full-text (1031 KB) | HTML Full-text | XML Full-text
Abstract
(+)-Neopeltolide is a marine macrolide natural product that exhibits potent antiproliferative activity against several human cancer cell lines. Previous study has established that this natural product primarily targets the complex III of the mitochondrial electron transport chain. However, the biochemical mode-of-actions of neopeltolide
[...] Read more.
(+)-Neopeltolide is a marine macrolide natural product that exhibits potent antiproliferative activity against several human cancer cell lines. Previous study has established that this natural product primarily targets the complex III of the mitochondrial electron transport chain. However, the biochemical mode-of-actions of neopeltolide have not been investigated in detail. Here we report that (−)-8,9-dehydroneopeltolide (8,9-DNP), a more accessible synthetic analogue, shows potent cytotoxicity against human promyelocytic leukemia HL-60 cells preferentially under energy stress conditions. Nuclear morphology analysis, as well as DNA ladder assay, indicated that 8,9-DNP induced significant nuclear condensation/fragmentation and DNA fragmentation, and these events could be suppressed by preincubating the cells with a pan-caspase inhibitor, N-benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD). Immunoblot analysis demonstrated the release of cytochrome c from the mitochondria and the cleavage of full-length caspase-3 and poly(ADP-ribose) polymerase (PARP). These results indicated that 8,9-DNP induced caspase-dependent apoptotic programmed cell death under energy stress conditions. It was also found that 8,9-DNP induced non-apoptotic cell death in the presence/absence of zVAD under energy stress conditions. Immunoblot analysis showed the intracytosolic release of apoptosis-inducing factor (AIF), although it did not further translocate to the nucleus. It appears most likely that, in the presence of zVAD, 8,9-DNP triggered necrotic cell death as a result of severe intracellular ATP depletion. Full article
(This article belongs to the collection Marine Compounds and Cancer) Printed Edition available
Open AccessArticle Agelasine D Suppresses RANKL-Induced Osteoclastogenesis via Down-Regulation of c-Fos, NFATc1 and NF-κB
Mar. Drugs 2014, 12(11), 5643-5656; doi:10.3390/md12115643
Received: 27 August 2014 / Revised: 31 October 2014 / Accepted: 12 November 2014 / Published: 24 November 2014
Cited by 6 | PDF Full-text (1316 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In the present study, we investigated the effect of agelasine D (AD) on osteoclastogenesis. Treatment of bone marrow macrophages (BMMs) with receptor activator of nuclear factor κB ligand (RANKL) resulted in a differentiation of BMMs into osteoclasts as evidenced by generation of tartrate-resistant
[...] Read more.
In the present study, we investigated the effect of agelasine D (AD) on osteoclastogenesis. Treatment of bone marrow macrophages (BMMs) with receptor activator of nuclear factor κB ligand (RANKL) resulted in a differentiation of BMMs into osteoclasts as evidenced by generation of tartrate-resistant acid phosphatase (TRAP)-positive, multinucleated cells and formation of pits in calcium phosphate-coated plates. However, RANKL-induced osteoclastogenesis was significantly suppressed by AD treatment. We also confirmed the increased mRNA and protein expression of osteoclastic markers, such as TRAP, cathepsin K and matrix metalloproteinase-9, during RANKL-induced osteoclast differentiation and this was down-regulated by AD treatment. Moreover, AD treatment significantly suppressed RANKL-induced mRNA expression of DC-STAMP and OC-STAMP and cell fusion of TRAP-positive mononuclear osteoclast precursors. In addition, AD suppressed RANKL-induced expression of transcription factors, c-Fos and nuclear factor of activated T cells c1 (NFATc1), which are important transcription factors involved in differentiation of BMMs into osteoclasts. Furthermore, RANKL-induced phosphorylation of extracellular signal-related kinase (ERK) and activation of NF-κB were also inhibited by AD treatment. Collectively, these results suggest that AD inhibits RANKL-induced osteoclastogenesis by down-regulation of multiple signaling pathways involving c-Fos, NFATc1, NF-κB and ERK. Our results also suggest that AD might be a potential therapeutic agent for prevention and treatment of osteoporosis. Full article
Figures

Open AccessArticle Exploring the Chemodiversity and Biological Activities of the Secondary Metabolites from the Marine Fungus Neosartorya pseudofischeri
Mar. Drugs 2014, 12(11), 5657-5676; doi:10.3390/md12115657
Received: 15 August 2014 / Revised: 12 November 2014 / Accepted: 17 November 2014 / Published: 24 November 2014
Cited by 16 | PDF Full-text (1250 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The production of fungal metabolites can be remarkably influenced by various cultivation parameters. To explore the biosynthetic potentials of the marine fungus, Neosartorya pseudofischeri, which was isolated from the inner tissue of starfish Acanthaster planci, glycerol-peptone-yeast extract (GlyPY) and glucose-peptone-yeast extract
[...] Read more.
The production of fungal metabolites can be remarkably influenced by various cultivation parameters. To explore the biosynthetic potentials of the marine fungus, Neosartorya pseudofischeri, which was isolated from the inner tissue of starfish Acanthaster planci, glycerol-peptone-yeast extract (GlyPY) and glucose-peptone-yeast extract (GluPY) media were used to culture this fungus. When cultured in GlyPY medium, this fungus produced two novel diketopiperazines, neosartins A and B (1 and 2), together with six biogenetically-related known diketopiperazines,1,2,3,4-tetrahydro-2, 3-dimethyl-1,4-dioxopyrazino[1,2-a]indole (3), 1,2,3,4-tetrahydro-2-methyl-3-methylen e-1,4-dioxopyrazino[1,2-a]indole (4), 1,2,3,4-tetrahydro-2-methyl-1,3,4-trioxopyrazino[1,2-a] indole (5), 6-acetylbis(methylthio)gliotoxin (10), bisdethiobis(methylthio)gliotoxin (11), didehydrobisdethiobis(methylthio)gliotoxin (12) and N-methyl-1H-indole-2-carboxamide (6). However, a novel tetracyclic-fused alkaloid, neosartin C (14), a meroterpenoid, pyripyropene A (15), gliotoxin (7) and five known gliotoxin analogues, acetylgliotoxin (8), reduced gliotoxin (9), 6-acetylbis(methylthio)gliotoxin (10), bisdethiobis(methylthio) gliotoxin (11) and bis-N-norgliovictin (13), were obtained when grown in glucose-containing medium (GluPY medium). This is the first report of compounds 3, 4, 6, 9, 10 and 12 as naturally occurring. Their structures were determined mainly by MS, 1D and 2D NMR data. The possible biosynthetic pathways of gliotoxin-related analogues and neosartin C were proposed. The antibacterial activity of compounds 214 and the cytotoxic activity of compounds 4, 5 and 713 were evaluated. Their structure-activity relationships are also preliminarily discussed. Full article
Figures

Open AccessArticle Delivery of Berberine Using Chitosan/Fucoidan-Taurine Conjugate Nanoparticles for Treatment of Defective Intestinal Epithelial Tight Junction Barrier
Mar. Drugs 2014, 12(11), 5677-5697; doi:10.3390/md12115677
Received: 6 September 2014 / Revised: 31 October 2014 / Accepted: 13 November 2014 / Published: 24 November 2014
Cited by 22 | PDF Full-text (1156 KB) | HTML Full-text | XML Full-text
Abstract
Bacterial-derived lipopolysaccharides (LPS) can cause defective intestinal barrier function and play an important role in the development of inflammatory bowel disease. In this study, a nanocarrier based on chitosan and fucoidan was developed for oral delivery of berberine (Ber). A sulfonated fucoidan, fucoidan-taurine
[...] Read more.
Bacterial-derived lipopolysaccharides (LPS) can cause defective intestinal barrier function and play an important role in the development of inflammatory bowel disease. In this study, a nanocarrier based on chitosan and fucoidan was developed for oral delivery of berberine (Ber). A sulfonated fucoidan, fucoidan-taurine (FD-Tau) conjugate, was synthesized and characterized by Fourier transform infrared (FTIR) spectroscopy. The FD-Tau conjugate was self-assembled with berberine and chitosan (CS) to form Ber-loaded CS/FD-Tau complex nanoparticles with high drug loading efficiency. Berberine release from the nanoparticles had fast release in simulated intestinal fluid (SIF, pH 7.4), while the release was slow in simulated gastric fluid (SGF, pH 2.0). The effect of the berberine-loaded nanoparticles in protecting intestinal tight-junction barrier function against nitric oxide and inflammatory cytokines released from LPS-stimulated macrophage was evaluated by determining the transepithelial electrical resistance (TEER) and paracellular permeability of a model macromolecule fluorescein isothiocyanate-dextran (FITC-dextran) in a Caco-2 cells/RAW264.7 cells co-culture system. Inhibition of redistribution of tight junction ZO-1 protein by the nanoparticles was visualized using confocal laser scanning microscopy (CLSM). The results suggest that the nanoparticles may be useful for local delivery of berberine to ameliorate LPS-induced intestinal epithelia tight junction disruption, and that the released berberine can restore barrier function in inflammatory and injured intestinal epithelial. Full article
(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan) Printed Edition available
Figures

Open AccessArticle Comparative Transcriptome Analysis of a Toxin-Producing Dinoflagellate Alexandrium catenella and Its Non-Toxic Mutant
Mar. Drugs 2014, 12(11), 5698-5718; doi:10.3390/md12115698
Received: 6 August 2014 / Revised: 11 October 2014 / Accepted: 29 October 2014 / Published: 24 November 2014
Cited by 16 | PDF Full-text (975 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The dinoflagellates and cyanobacteria are two major kingdoms of life producing paralytic shellfish toxins (PSTs), a large group of neurotoxic alkaloids causing paralytic shellfish poisonings around the world. In contrast to the well elucidated PST biosynthetic genes in cyanobacteria, little is known about
[...] Read more.
The dinoflagellates and cyanobacteria are two major kingdoms of life producing paralytic shellfish toxins (PSTs), a large group of neurotoxic alkaloids causing paralytic shellfish poisonings around the world. In contrast to the well elucidated PST biosynthetic genes in cyanobacteria, little is known about the dinoflagellates. This study compared transcriptome profiles of a toxin-producing dinoflagellate, Alexandrium catenella (ACHK-T), and its non-toxic mutant form (ACHK-NT) using RNA-seq. All clean reads were assembled de novo into a total of 113,674 unigenes, and 66,812 unigenes were annotated in the known databases. Out of them, 35 genes were found to express differentially between the two strains. The up-regulated genes in ACHK-NT were involved in photosynthesis, carbon fixation and amino acid metabolism processes, indicating that more carbon and energy were utilized for cell growth. Among the down-regulated genes, expression of a unigene assigned to the long isoform of sxtA, the initiator of toxin biosynthesis in cyanobacteria, was significantly depressed, suggesting that this long transcript of sxtA might be directly involved in toxin biosynthesis and its depression resulted in the loss of the ability to synthesize PSTs in ACHK-NT. In addition, 101 putative homologs of 12 cyanobacterial sxt genes were identified, and the sxtO and sxtZ genes were identified in dinoflagellates for the first time. The findings of this study should shed light on the biosynthesis of PSTs in the dinoflagellates. Full article
(This article belongs to the Special Issue Marine Shellfish Toxins)

Review

Jump to: Research

Open AccessReview Bioproduction of Chitooligosaccharides: Present and Perspectives
Mar. Drugs 2014, 12(11), 5328-5356; doi:10.3390/md12115328
Received: 19 August 2014 / Revised: 20 October 2014 / Accepted: 21 October 2014 / Published: 28 October 2014
Cited by 32 | PDF Full-text (357 KB) | HTML Full-text | XML Full-text
Abstract
Chitin and chitosan oligosaccharides (COS) have been traditionally obtained by chemical digestion with strong acids. In light of the difficulties associated with these traditional production processes, environmentally compatible and reproducible production alternatives are desirable. Unlike chemical digestion, biodegradation of chitin and chitosan by
[...] Read more.
Chitin and chitosan oligosaccharides (COS) have been traditionally obtained by chemical digestion with strong acids. In light of the difficulties associated with these traditional production processes, environmentally compatible and reproducible production alternatives are desirable. Unlike chemical digestion, biodegradation of chitin and chitosan by enzymes or microorganisms does not require the use of toxic chemicals or excessive amounts of wastewater. Enzyme preparations with chitinase, chitosanase, and lysozymeare primarily used to hydrolyze chitin and chitosan. Commercial preparations of cellulase, protease, lipase, and pepsin provide another opportunity for oligosaccharide production. In addition to their hydrolytic activities, the transglycosylation activity of chitinolytic enzymes might be exploited for the synthesis of desired chitin oligomers and their derivatives. Chitin deacetylase is also potentially useful for the preparation of oligosaccharides. Recently, direct production of oligosaccharides from chitin and crab shells by a combination of mechanochemical grinding and enzymatic hydrolysis has been reported. Together with these, other emerging technologies such as direct degradation of chitin from crustacean shells and microbial cell walls, enzymatic synthesis of COS from small building blocks, and protein engineering technology for chitin-related enzymes have been discussed as the most significant challenge for industrial application. Full article
(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan) Printed Edition available
Open AccessReview Reactive Oxygen Species and Autophagy Modulation in Non-Marine Drugs and Marine Drugs
Mar. Drugs 2014, 12(11), 5408-5424; doi:10.3390/md12115408
Received: 4 September 2014 / Revised: 6 November 2014 / Accepted: 7 November 2014 / Published: 13 November 2014
Cited by 17 | PDF Full-text (396 KB) | HTML Full-text | XML Full-text
Abstract
It is becoming more understandable that an existing challenge for translational research is the development of pharmaceuticals that appropriately target reactive oxygen species (ROS)-mediated molecular networks in cancer cells. In line with this approach, there is an overwhelmingly increasing list of many non-marine
[...] Read more.
It is becoming more understandable that an existing challenge for translational research is the development of pharmaceuticals that appropriately target reactive oxygen species (ROS)-mediated molecular networks in cancer cells. In line with this approach, there is an overwhelmingly increasing list of many non-marine drugs and marine drugs reported to be involved in inhibiting and suppressing cancer progression through ROS-mediated cell death. In this review, we describe the strategy of oxidative stress-based therapy and connect the ROS modulating effect to the regulation of apoptosis and autophagy. Finally, we focus on exploring the function and mechanism of cancer therapy by the autophagy modulators including inhibitors and inducers from non-marine drugs and marine drugs. Full article
(This article belongs to the collection Marine Compounds and Cancer) Printed Edition available
Open AccessReview Emerging Biomedical Applications of Nano-Chitins and Nano-Chitosans Obtained via Advanced Eco-Friendly Technologies from Marine Resources
Mar. Drugs 2014, 12(11), 5468-5502; doi:10.3390/md12115468
Received: 10 October 2014 / Revised: 2 November 2014 / Accepted: 3 November 2014 / Published: 19 November 2014
Cited by 42 | PDF Full-text (1990 KB) | HTML Full-text | XML Full-text
Abstract
The present review article is intended to direct attention to the technological advances made in the 2010–2014 quinquennium for the isolation and manufacture of nanofibrillar chitin and chitosan. Otherwise called nanocrystals or whiskers, n-chitin and n-chitosan are obtained either by mechanical chitin disassembly
[...] Read more.
The present review article is intended to direct attention to the technological advances made in the 2010–2014 quinquennium for the isolation and manufacture of nanofibrillar chitin and chitosan. Otherwise called nanocrystals or whiskers, n-chitin and n-chitosan are obtained either by mechanical chitin disassembly and fibrillation optionally assisted by sonication, or by e-spinning of solutions of polysaccharides often accompanied by poly(ethylene oxide) or poly(caprolactone). The biomedical areas where n-chitin may find applications include hemostasis and wound healing, regeneration of tissues such as joints and bones, cell culture, antimicrobial agents, and dermal protection. The biomedical applications of n-chitosan include epithelial tissue regeneration, bone and dental tissue regeneration, as well as protection against bacteria, fungi and viruses. It has been found that the nano size enhances the performances of chitins and chitosans in all cases considered, with no exceptions. Biotechnological approaches will boost the applications of the said safe, eco-friendly and benign nanomaterials not only in these fields, but also for biosensors and in targeted drug delivery areas. Full article
(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan) Printed Edition available
Open AccessReview Marine Invertebrate Xenobiotic-Activated Nuclear Receptors: Their Application as Sensor Elements in High-Throughput Bioassays for Marine Bioactive Compounds
Mar. Drugs 2014, 12(11), 5590-5618; doi:10.3390/md12115590
Received: 20 May 2014 / Revised: 31 October 2014 / Accepted: 11 November 2014 / Published: 24 November 2014
Cited by 5 | PDF Full-text (467 KB) | HTML Full-text | XML Full-text
Abstract
Developing high-throughput assays to screen marine extracts for bioactive compounds presents both conceptual and technical challenges. One major challenge is to develop assays that have well-grounded ecological and evolutionary rationales. In this review we propose that a specific group of ligand-activated transcription factors
[...] Read more.
Developing high-throughput assays to screen marine extracts for bioactive compounds presents both conceptual and technical challenges. One major challenge is to develop assays that have well-grounded ecological and evolutionary rationales. In this review we propose that a specific group of ligand-activated transcription factors are particularly well-suited to act as sensors in such bioassays. More specifically, xenobiotic-activated nuclear receptors (XANRs) regulate transcription of genes involved in xenobiotic detoxification. XANR ligand-binding domains (LBDs) may adaptively evolve to bind those bioactive, and potentially toxic, compounds to which organisms are normally exposed to through their specific diets. A brief overview of the function and taxonomic distribution of both vertebrate and invertebrate XANRs is first provided. Proof-of-concept experiments are then described which confirm that a filter-feeding marine invertebrate XANR LBD is activated by marine bioactive compounds. We speculate that increasing access to marine invertebrate genome sequence data, in combination with the expression of functional recombinant marine invertebrate XANR LBDs, will facilitate the generation of high-throughput bioassays/biosensors of widely differing specificities, but all based on activation of XANR LBDs. Such assays may find application in screening marine extracts for bioactive compounds that could act as drug lead compounds. Full article
Figures

Open AccessReview Preparation of Chitosan Nanocompositeswith a Macroporous Structure by Unidirectional Freezing and Subsequent Freeze-Drying
Mar. Drugs 2014, 12(11), 5619-5642; doi:10.3390/md12115619
Received: 11 October 2014 / Revised: 12 November 2014 / Accepted: 13 November 2014 / Published: 24 November 2014
Cited by 14 | PDF Full-text (2235 KB) | HTML Full-text | XML Full-text
Abstract
Chitosan is the N-deacetylated derivative of chitin, a naturally abundant mucopolysaccharide that consists of 2-acetamido-2-deoxy-β-d-glucose through a β (1→4) linkage and is found in nature as the supporting material of crustaceans, insects, etc. Chitosan has been strongly recommended as a suitable functional
[...] Read more.
Chitosan is the N-deacetylated derivative of chitin, a naturally abundant mucopolysaccharide that consists of 2-acetamido-2-deoxy-β-d-glucose through a β (1→4) linkage and is found in nature as the supporting material of crustaceans, insects, etc. Chitosan has been strongly recommended as a suitable functional material because of its excellent biocompatibility, biodegradability, non-toxicity, and adsorption properties. Boosting all these excellent properties to obtain unprecedented performances requires the core competences of materials chemists to design and develop novel processing strategies that ultimately allow tailoring the structure and/or the composition of the resulting chitosan-based materials. For instance, the preparation of macroporous materials is challenging in catalysis, biocatalysis and biomedicine, because the resulting materials will offer a desirable combination of high internal reactive surface area and straightforward molecular transport through broad “highways” leading to such a surface. Moreover, chitosan-based composites made of two or more distinct components will produce structural or functional properties not present in materials composed of one single component. Our group has been working lately on cryogenic processes based on the unidirectional freezing of water slurries and/or hydrogels, the subsequent freeze-drying of which produce macroporous materials with a well-patterned structure. We have applied this process to different gels and colloidal suspensions of inorganic, organic, and hybrid materials. In this review, we will describe the application of the process to chitosan solutions and gels typically containing a second component (e.g., metal and ceramic nanoparticles, or carbon nanotubes) for the formation of chitosan nanocomposites with a macroporous structure. We will also discuss the role played by this tailored composition and structure in the ultimate performance of these materials. Full article
(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan) Printed Edition available
Back to Top