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 16, Issue 3 (March 2018)

  • 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.
Cover Story (view full-size image) The chemical composition and properties of spongin - halogenated scleroprotein of commercial [...] Read more.
View options order results:
result details:
Displaying articles 1-24
Export citation of selected articles as:
Open AccessArticle Identification and Characterization of Mycemycin Biosynthetic Gene Clusters in Streptomyces olivaceus FXJ8.012 and Streptomyces sp. FXJ1.235
Mar. Drugs 2018, 16(3), 98; https://doi.org/10.3390/md16030098
Received: 13 February 2018 / Revised: 7 March 2018 / Accepted: 15 March 2018 / Published: 20 March 2018
PDF Full-text (2155 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Mycemycins A–E are new members of the dibenzoxazepinone (DBP) family, derived from the gntR gene-disrupted deep sea strain Streptomyces olivaceus FXJ8.012Δ1741 and the soil strain Streptomyces sp. FXJ1.235. In this paper, we report the identification of the gene clusters and pathways’ inference for
[...] Read more.
Mycemycins A–E are new members of the dibenzoxazepinone (DBP) family, derived from the gntR gene-disrupted deep sea strain Streptomyces olivaceus FXJ8.012Δ1741 and the soil strain Streptomyces sp. FXJ1.235. In this paper, we report the identification of the gene clusters and pathways’ inference for mycemycin biosynthesis in the two strains. Bioinformatics analyses of the genome sequences of S. olivaceus FXJ8.012Δ1741 and S. sp. FXJ1.235 predicted two divergent mycemycin gene clusters, mym and mye, respectively. Heterologous expression of the key enzyme genes of mym and genetic manipulation of mye as well as a feeding study in S. sp. FXJ1.235 confirmed the gene clusters and led to the proposed biosynthetic pathways for mycemycins. To the best of our knowledge, this is the first report on DBP biosynthetic gene clusters and pathways. Full article
(This article belongs to the Special Issue Microbial Gene Clusters of Marine Origin)
Figures

Figure 1

Open AccessArticle Function-Oriented Synthesis of Marine Phidianidine Derivatives as Potential PTP1B Inhibitors with Specific Selectivity
Mar. Drugs 2018, 16(3), 97; https://doi.org/10.3390/md16030097
Received: 25 January 2018 / Revised: 7 March 2018 / Accepted: 7 March 2018 / Published: 20 March 2018
PDF Full-text (4731 KB) | HTML Full-text | XML Full-text
Abstract
Phidianidines A and B are two novel marine indole alkaloids bearing an uncommon 1,2,4-oxadiazole ring and exhibiting various biological activities. Our previous research showed that the synthesized phidianidine analogs had the potential to inhibit the activity of protein tyrosine phosphatase 1B (PTP1B), a
[...] Read more.
Phidianidines A and B are two novel marine indole alkaloids bearing an uncommon 1,2,4-oxadiazole ring and exhibiting various biological activities. Our previous research showed that the synthesized phidianidine analogs had the potential to inhibit the activity of protein tyrosine phosphatase 1B (PTP1B), a validated target for Type II diabetes, which indicates that these analogs are worth further structural modification. Therefore, in this paper, a series of phidianidine derivatives were designed and rapidly synthesized with a function-oriented synthesis (FOS) strategy. Their inhibitory effects on PTP1B and T-cell protein tyrosine phosphatase (TCPTP) were evaluated, and several compounds displayed significant inhibitory potency and specific selectivity over PTP1B. The structure–activity relationship (SAR) and molecular docking analyses are also described. Full article
Figures

Figure 1

Open AccessArticle GABA and GABA-Alanine from the Red Microalgae Rhodosorus marinus Exhibit a Significant Neuro-Soothing Activity through Inhibition of Neuro-Inflammation Mediators and Positive Regulation of TRPV1-Related Skin Sensitization
Mar. Drugs 2018, 16(3), 96; https://doi.org/10.3390/md16030096
Received: 14 February 2018 / Revised: 9 March 2018 / Accepted: 13 March 2018 / Published: 17 March 2018
PDF Full-text (2379 KB) | HTML Full-text | XML Full-text
Abstract
The aim of the present study was to investigate the neuro-soothing activity of a water-soluble hydrolysate obtained from the red microalgae Rhodosorus marinus Geitler (Stylonemataceae). Transcriptomic analysis performed on ≈100 genes related to skin biological functions firstly revealed that the crude Rhodosorus marinus
[...] Read more.
The aim of the present study was to investigate the neuro-soothing activity of a water-soluble hydrolysate obtained from the red microalgae Rhodosorus marinus Geitler (Stylonemataceae). Transcriptomic analysis performed on ≈100 genes related to skin biological functions firstly revealed that the crude Rhodosorus marinus extract was able to significantly negatively modulate specific genes involved in pro-inflammation (interleukin 1α encoding gene, IL1A) and pain detection related to tissue inflammation (nerve growth factor NGF and its receptor NGFR). An in vitro model of normal human keratinocytes was then used to evaluate the ability of the Rhodosorus marinus extract to control the release of neuro-inflammation mediators under phorbol myristate acetate (PMA)-induced inflammatory conditions. The extract incorporated at 1% and 3% significantly inhibited the release of IL-1α and NGF secretion. These results were confirmed in a co-culture system of reconstructed human epithelium and normal human epidermal keratinocytes on which a cream formulated with the Rhodosorus marinus extract at 1% and 3% was topically applied after systemic induction of neuro-inflammation. Finally, an in vitro model of normal human astrocytes was developed for the evaluation of transient receptor potential vanilloid 1 (TRPV1) receptor modulation, mimicking pain sensing related to neuro-inflammation as observed in sensitive skins. Treatment with the Rhodosorus marinus extract at 1% and 3% significantly decreased PMA-mediated TRPV1 over-expression. In parallel with these biological experiments, the crude Rhodosorus marinus extract was fractionated by centrifugal partition chromatography (CPC) and chemically profiled by a recently developed 13C NMR-based dereplication method. The CPC-generated fractions as well as pure metabolites were tested again in vitro in an attempt to identify the biologically active constituents involved in the neuro-soothing activity of the Rhodosorus marinus extract. Two active molecules, namely, γ-aminobutyric acid (GABA) and its structural derivative GABA-alanine, demonstrated a strong capacity to positively regulate skin sensitization mechanisms related to the TRPV1 receptors under PMA-induced inflammatory conditions, therefore providing interesting perspectives for the treatment of sensitive skins, atopia, dermatitis, or psoriasis. Full article
Figures

Figure 1

Open AccessFeature PaperArticle Phocoenamicins B and C, New Antibacterial Spirotetronates Isolated from a Marine Micromonospora sp.
Mar. Drugs 2018, 16(3), 95; https://doi.org/10.3390/md16030095
Received: 20 February 2018 / Revised: 13 March 2018 / Accepted: 14 March 2018 / Published: 16 March 2018
PDF Full-text (2540 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Phocoenamicins B and C (1 and 2), together with the known spirotetronate phocoenamicin (3), were isolated from cultures of Micromonospora sp. The acetone extract from a culture of this strain, isolated from marine sediments collected in the Canary Islands,
[...] Read more.
Phocoenamicins B and C (1 and 2), together with the known spirotetronate phocoenamicin (3), were isolated from cultures of Micromonospora sp. The acetone extract from a culture of this strain, isolated from marine sediments collected in the Canary Islands, displayed activity against methicillin-resistant Staphylococcus aureus (MRSA), Mycobacterium tuberculosis H37Ra and Mycobacterium bovis. Bioassay-guided fractionation of this extract using SP207ss column chromatography and preparative reversed-phased HPLC led to the isolation of the new compounds 1 and 2 belonging to the spirotetronate class of polyketides. Their structures were determined using a combination of HRMS, 1D and 2D NMR experiments and comparison with the spectra reported for phocoenamicin. Antibacterial activity tests of the pure compounds against these pathogens revealed minimal inhibitory concentration (MIC) values ranging from 4 to 64 µg/mL for MRSA, and 16 to 32 µg/mL for M. tuberculosis H37Ra, with no significant activity found against M. bovis and vancomycin-resistant Enterococcus faecium (VRE) at concentrations below 128 µg/mL, and weak activity detected against Bacillus subtilis grown on agar plates. Full article
(This article belongs to the Special Issue Isolation and Structure Elucidation of Marine Secondary Metabolites)
Figures

Graphical abstract

Open AccessArticle Anti-BACE1 and Antimicrobial Activities of Steroidal Compounds Isolated from Marine Urechis unicinctus
Mar. Drugs 2018, 16(3), 94; https://doi.org/10.3390/md16030094
Received: 27 December 2017 / Revised: 1 February 2018 / Accepted: 12 March 2018 / Published: 14 March 2018
Cited by 1 | PDF Full-text (1196 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The human β-site amyloid cleaving enzyme (BACE1) has been considered as an effective drug target for treatment of Alzheimer’s disease (AD). In this study, Urechis unicinctus (U. unicinctus), which is a Far East specialty food known as innkeeper worm, ethanol extract was
[...] Read more.
The human β-site amyloid cleaving enzyme (BACE1) has been considered as an effective drug target for treatment of Alzheimer’s disease (AD). In this study, Urechis unicinctus (U. unicinctus), which is a Far East specialty food known as innkeeper worm, ethanol extract was studied by bioassay-directed fractionation and isolation to examine its potential β-site amyloid cleaving enzyme inhibitory and antimicrobial activity. The following compounds were characterized: hecogenin, cholest-4-en-3-one, cholesta-4,6-dien-3-ol, and hurgadacin. These compounds were identified by their mass spectrometry, 1H, and 13C NMR spectral data, comparing those data with NIST/EPA/NIH Mass spectral database (NIST11) and published values. Hecogenin and cholest-4-en-3-one showed significant inhibitory activity against BACE1 with EC50 values of 116.3 and 390.6 µM, respectively. Cholesta-4,6-dien-3-ol and hurgadacin showed broad spectrum antimicrobial activity, particularly strongly against Escherichia coli (E. coli), Salmonella enterica (S. enterica), Pasteurella multocida (P. multocida), and Physalospora piricola (P. piricola), with minimal inhibitory concentration (MIC) ranging from 0.46 to 0.94 mg/mL. This is the first report regarding those four known compounds that were isolated from U. unicinctus and their anti-BACE1 and antimicrobial activity, highlighting the fact that known natural compounds may be a critical source of new medicine leads. These findings provide scientific evidence for potential application of those bioactive compounds for the development of AD drugs and antimicrobial agents. Full article
Figures

Graphical abstract

Open AccessArticle Anti-Inflammatory Polyoxygenated Steroids from the Soft Coral Lobophytum michaelae
Mar. Drugs 2018, 16(3), 93; https://doi.org/10.3390/md16030093
Received: 26 January 2018 / Revised: 8 March 2018 / Accepted: 9 March 2018 / Published: 13 March 2018
PDF Full-text (2045 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Three new polyoxygenated steroids, michosterols A–C (13), and four known compounds (47) were isolated from the ethyl acetate (EtOAc) extract of the soft coral Lobophytum michaelae, collected off the coast of Taitung. The structures
[...] Read more.
Three new polyoxygenated steroids, michosterols A–C (13), and four known compounds (47) were isolated from the ethyl acetate (EtOAc) extract of the soft coral Lobophytum michaelae, collected off the coast of Taitung. The structures of the new compounds were elucidated on the basis of spectroscopic analyses and comparison of the nuclear magnetic resonance (NMR) data with related steroids. The cytotoxicity of compounds 13 against the proliferation of a limited panel of cancer cell lines was assayed. Compound 1 was found to display moderate cytotoxicity against adenocarcinomic human alveolar basal epithelial (A549) cancer cells. It also exhibited potent anti-inflammatory activity by suppressing superoxide anion generation and elastase release in N-formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLP/CB)-stimulated human neutrophils. Furthermore, 3 could effectively inhibit elastase release, as well. Full article
(This article belongs to the Special Issue Natural Products from Coral Reef Organisms)
Figures

Graphical abstract

Open AccessArticle Cytotoxic Polyhydroxysteroidal Glycosides from Starfish Culcita novaeguineae
Mar. Drugs 2018, 16(3), 92; https://doi.org/10.3390/md16030092
Received: 7 February 2018 / Revised: 28 February 2018 / Accepted: 10 March 2018 / Published: 13 March 2018
Cited by 1 | PDF Full-text (679 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Four new polyhydroxysteroidal glycosides—culcinosides A–D (1, 2, 4, and 7)—along with three known compounds—echinasteroside C (3), linckoside F (5), and linckoside L3 (6)—were isolated from the ethanol extract of starfish Culcita novaeguineae
[...] Read more.
Four new polyhydroxysteroidal glycosides—culcinosides A–D (1, 2, 4, and 7)—along with three known compounds—echinasteroside C (3), linckoside F (5), and linckoside L3 (6)—were isolated from the ethanol extract of starfish Culcita novaeguineae collected from the Xisha Islands of the South China Sea. The structures of new compounds were elucidated through extensive spectroscopic studies and chemical evidence, especially two-dimensional (2D) NMR techniques. The cytotoxicity of the new compounds against human glioblastoma cell lines U87, U251, and SHG44 were evaluated. Full article
(This article belongs to the Special Issue Marine Glycosides)
Figures

Figure 1

Open AccessArticle Biphasic Scaffolds from Marine Collagens for Regeneration of Osteochondral Defects
Mar. Drugs 2018, 16(3), 91; https://doi.org/10.3390/md16030091
Received: 10 January 2018 / Revised: 5 March 2018 / Accepted: 10 March 2018 / Published: 13 March 2018
Cited by 2 | PDF Full-text (12125 KB) | HTML Full-text | XML Full-text
Abstract
Background: Collagens of marine origin are applied increasingly as alternatives to mammalian collagens in tissue engineering. The aim of the present study was to develop a biphasic scaffold from exclusively marine collagens supporting both osteogenic and chondrogenic differentiation and to find a suitable
[...] Read more.
Background: Collagens of marine origin are applied increasingly as alternatives to mammalian collagens in tissue engineering. The aim of the present study was to develop a biphasic scaffold from exclusively marine collagens supporting both osteogenic and chondrogenic differentiation and to find a suitable setup for in vitro chondrogenic and osteogenic differentiation of human mesenchymal stroma cells (hMSC). Methods: Biphasic scaffolds from biomimetically mineralized salmon collagen and fibrillized jellyfish collagen were fabricated by joint freeze-drying and crosslinking. Different experiments were performed to analyze the influence of cell density and TGF-β on osteogenic differentiation of the cells in the scaffolds. Gene expression analysis and analysis of cartilage extracellular matrix components were performed and activity of alkaline phosphatase was determined. Furthermore, histological sections of differentiated cells in the biphasic scaffolds were analyzed. Results: Stable biphasic scaffolds from two different marine collagens were prepared. An in vitro setup for osteochondral differentiation was developed involving (1) different seeding densities in the phases; (2) additional application of alginate hydrogel in the chondral part; (3) pre-differentiation and sequential seeding of the scaffolds and (4) osteochondral medium. Spatially separated osteogenic and chondrogenic differentiation of hMSC was achieved in this setup, while osteochondral medium in combination with the biphasic scaffolds alone was not sufficient to reach this ambition. Conclusions: Biphasic, but monolithic scaffolds from exclusively marine collagens are suitable for the development of osteochondral constructs. Full article
(This article belongs to the Special Issue Collagen from Marine Biological Source and Medical Applications)
Figures

Figure 1

Open AccessCommunication New Naphthoquinone Terpenoids from Marine Actinobacterium, Streptomyces sp. CNQ-509
Mar. Drugs 2018, 16(3), 90; https://doi.org/10.3390/md16030090
Received: 30 January 2018 / Revised: 8 March 2018 / Accepted: 9 March 2018 / Published: 12 March 2018
Cited by 3 | PDF Full-text (1112 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A member of the marine streptomycete clade MAR4, Streptomyces sp. CNQ-509, has genetic potential for the biosynthesis of hybrid isoprenoids and produces several meroterpenoids such as naphterpin, nitropyrrolin and marinophenazine. Our research on the strain CNQ-509 led to the isolation of two new
[...] Read more.
A member of the marine streptomycete clade MAR4, Streptomyces sp. CNQ-509, has genetic potential for the biosynthesis of hybrid isoprenoids and produces several meroterpenoids such as naphterpin, nitropyrrolin and marinophenazine. Our research on the strain CNQ-509 led to the isolation of two new naphterpin derivatives (1 and 2) comprised of naphthoquinone and geranyl moieties along with the known terpenoid, debromomarinone. The two-dimensional structure of these compounds was determined through spectral data analysis using data from NMR, MS and UV spectroscopy. Furthermore, the full structures of 1 and 2 including absolute configurations were unequivocally established by a combination of NMR experiments and chemical modifications. Full article
(This article belongs to the Special Issue Natural Products from Marine Actinomycetes)
Figures

Graphical abstract

Open AccessArticle Synthesis and Biological Evaluation of a New Structural Simplified Analogue of cADPR, a Calcium-Mobilizing Secondary Messenger Firstly Isolated from Sea Urchin Eggs
Mar. Drugs 2018, 16(3), 89; https://doi.org/10.3390/md16030089
Received: 2 January 2018 / Revised: 5 March 2018 / Accepted: 7 March 2018 / Published: 10 March 2018
Cited by 1 | PDF Full-text (1557 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Herein, we reported on the synthesis of cpIPP, which is a new structurally-reduced analogue of cyclic ADP-ribose (cADPR), a potent Ca2+-releasing secondary messenger that was firstly isolated from sea urchin eggs extracts. To obtain cpIPP the “northern” ribose of cADPR was
[...] Read more.
Herein, we reported on the synthesis of cpIPP, which is a new structurally-reduced analogue of cyclic ADP-ribose (cADPR), a potent Ca2+-releasing secondary messenger that was firstly isolated from sea urchin eggs extracts. To obtain cpIPP the “northern” ribose of cADPR was replaced by a pentyl chain and the pyrophosphate moiety by a phophono-phosphate anhydride. The effect of the presence of the new phosphono-phosphate bridge on the intracellular Ca2+ release induced by cpIPP was assessed in PC12 neuronal cells in comparison with the effect of the pyrophosphate bridge of the structurally related cyclic N1-butylinosine diphosphate analogue (cbIDP), which was previously synthesized in our laboratories, and with that of the linear precursor of cpIPP, which, unexpectedly, revealed to be the only one provided with Ca2+ release properties. Full article
(This article belongs to the Special Issue Marine Secondary Metabolite II, 2017)
Figures

Figure 1

Open AccessReview Marine Spongin: Naturally Prefabricated 3D Scaffold-Based Biomaterial
Mar. Drugs 2018, 16(3), 88; https://doi.org/10.3390/md16030088
Received: 30 January 2018 / Revised: 6 March 2018 / Accepted: 6 March 2018 / Published: 9 March 2018
Cited by 1 | PDF Full-text (8588 KB) | HTML Full-text | XML Full-text
Abstract
The biosynthesis, chemistry, structural features and functionality of spongin as a halogenated scleroprotein of keratosan demosponges are still paradigms. This review has the principal goal of providing thorough and comprehensive coverage of spongin as a naturally prefabricated 3D biomaterial with multifaceted applications. The
[...] Read more.
The biosynthesis, chemistry, structural features and functionality of spongin as a halogenated scleroprotein of keratosan demosponges are still paradigms. This review has the principal goal of providing thorough and comprehensive coverage of spongin as a naturally prefabricated 3D biomaterial with multifaceted applications. The history of spongin’s discovery and use in the form of commercial sponges, including their marine farming strategies, have been analyzed and are discussed here. Physicochemical and material properties of spongin-based scaffolds are also presented. The review also focuses on prospects and trends in applications of spongin for technology, materials science and biomedicine. Special attention is paid to applications in tissue engineering, adsorption of dyes and extreme biomimetics. Full article
(This article belongs to the Special Issue Marine Biomimetics)
Figures

Figure 1

Open AccessArticle Fluostatins M–Q Featuring a 6-5-6-6 Ring Skeleton and High Oxidized A-Rings from Marine Streptomyces sp. PKU-MA00045
Mar. Drugs 2018, 16(3), 87; https://doi.org/10.3390/md16030087
Received: 6 February 2018 / Revised: 1 March 2018 / Accepted: 5 March 2018 / Published: 9 March 2018
Cited by 3 | PDF Full-text (1717 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Aromatic polyketides from marine actinomycetes have received increasing attention due to their unusual structures and potent bioactivities. Compared to their terrestrial counterparts, marine aromatic polyketides have been less discovered and their structural and biological diversities are far from being fully investigated. In this
[...] Read more.
Aromatic polyketides from marine actinomycetes have received increasing attention due to their unusual structures and potent bioactivities. Compared to their terrestrial counterparts, marine aromatic polyketides have been less discovered and their structural and biological diversities are far from being fully investigated. In this study, we employed a PCR-based genome mining method to discover aromatic polyketides in our marine bacteria collection. Five new atypical angucyclinones, fluostatins M–Q (15) featuring a unique 6-5-6-6 ring skeleton, were discovered from one “positive” Streptomyces sp. PKU-MA00045. The structures of fluostatins M–Q (15) were elucidated based on comprehensive spectroscopic analyses and the crystallographic structure of fluostatin P (4), which contains the most oxidized A-ring, was solved by X-ray diffraction analysis with Cu Kα radiation. Compared to the published 16 fluostatin analogues, fluostatins M–Q (15) contained a different methoxy group attached at C-7 and hydroxy group attached at C-4, enriching the structural diversity of aromatic polyketides from marine actinomycetes. Genome sequencing of Streptomyces sp. PKU-MA00045 revealed the biosynthetic gene cluster of fluostatins M–Q (15), which contained different genes and gene organizations compared to known fluostatin gene clusters, facilitating the investigation of the biosynthesis of the unique 6-5-6-6 ring skeleton in all fluostatins. Full article
(This article belongs to the Special Issue Natural Products from Marine Actinomycetes)
Figures

Figure 1

Open AccessArticle Purification and Characterization of a Novel Alginate Lyase from the Marine Bacterium Bacillus sp. Alg07
Mar. Drugs 2018, 16(3), 86; https://doi.org/10.3390/md16030086
Received: 9 February 2018 / Revised: 28 February 2018 / Accepted: 5 March 2018 / Published: 9 March 2018
Cited by 3 | PDF Full-text (1968 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Alginate oligosaccharides with different bioactivities can be prepared through the specific degradation of alginate by alginate lyases. Therefore, alginate lyases that can be used to degrade alginate under mild conditions have recently attracted public attention. Although various types of alginate lyases have been
[...] Read more.
Alginate oligosaccharides with different bioactivities can be prepared through the specific degradation of alginate by alginate lyases. Therefore, alginate lyases that can be used to degrade alginate under mild conditions have recently attracted public attention. Although various types of alginate lyases have been discovered and characterized, few can be used in industrial production. In this study, AlgA, a novel alginate lyase with high specific activity, was purified from the marine bacterium Bacillus sp. Alg07. AlgA had a molecular weight of approximately 60 kDa, an optimal temperature of 40 °C, and an optimal pH of 7.5. The activity of AlgA was dependent on sodium chloride and could be considerably enhanced by Mg2+ or Ca2+. Under optimal conditions, the activity of AlgA reached up to 8306.7 U/mg, which is the highest activity recorded for alginate lyases. Moreover, the enzyme was stable over a broad pH range (5.0–10.0), and its activity negligibly changed after 24 h of incubation at 40 °C. AlgA exhibited high activity and affinity toward poly-β-d-mannuronate (polyM). These characteristics suggested that AlgA is an endolytic polyM-specific alginate lyase (EC 4.2.2.3). The products of alginate and polyM degradation by AlgA were purified and identified through fast protein liquid chromatography and electrospray ionization mass spectrometry, which revealed that AlgA mainly produced disaccharides, trisaccharides, and tetrasaccharide from alginate and disaccharides and trisaccharides from polyM. Therefore, the novel lysate AlgA has potential applications in the production of mannuronic oligosaccharides and poly-α-l-guluronate blocks from alginate. Full article
Figures

Figure 1

Open AccessArticle Marine Bacterial Polysaccharide EPS11 Inhibits Cancer Cell Growth via Blocking Cell Adhesion and Stimulating Anoikis
Mar. Drugs 2018, 16(3), 85; https://doi.org/10.3390/md16030085
Received: 9 January 2018 / Revised: 25 February 2018 / Accepted: 6 March 2018 / Published: 8 March 2018
PDF Full-text (10029 KB) | HTML Full-text | XML Full-text
Abstract
Tumor cells that acquire metastatic potential have developed resistance to anoikis, a cell death process, after detachment from their primary site to the second organ. In this study, we investigated the molecular mechanisms of a novel marine bacterial polysaccharide EPS11 which exerts its
[...] Read more.
Tumor cells that acquire metastatic potential have developed resistance to anoikis, a cell death process, after detachment from their primary site to the second organ. In this study, we investigated the molecular mechanisms of a novel marine bacterial polysaccharide EPS11 which exerts its cytotoxic effects through affecting cancer cell adhesion and anoikis. Firstly, we found that EPS11 could significantly affect cell proliferation and block cell adhesion in A549 cells. We further demonstrated that the expression of several cell adhesion associated proteins is downregulated and the filiform structures of cancer cells are destroyed after EPS11 treatment. Interestingly, the destruction of filiform structures in A549 cells by EPS11 is in a dose-dependent manner, and the inhibitory tendency is very consistent with that observed in the cell adhesion assay, which confirms that filiform structures play important roles in modulating cell adhesion. Moreover, we showed that EPS11 induces apoptosis of A549 cells through stimulating βIII-tubulin associated anoikis: (i) EPS11 inhibits the expression of βIII-tubulin in both transcription and translation levels; and (ii) EPS11 treatment dramatically decreases the phosphorylation of protein kinase B (PKB or AKT), a critical downstream effector of βIII-tubulin. Importantly, EPS11 evidently inhibits the growth of A549-derived tumor xenografts in vivo. Thus, our results suggest that EPS11 may be a potential candidate for human non-small cell lung carcinoma treatment via blocking filiform structure mediated adhesion and stimulating βIII-tubulin associated anoikis. Full article
(This article belongs to the Special Issue Connection of Marine Natural Products and Cell Apoptosis)
Figures

Graphical abstract

Open AccessArticle New Crambescidin-Type Alkaloids from the Indonesian Marine Sponge Clathria bulbotoxa
Mar. Drugs 2018, 16(3), 84; https://doi.org/10.3390/md16030084
Received: 16 February 2018 / Revised: 1 March 2018 / Accepted: 5 March 2018 / Published: 8 March 2018
Cited by 1 | PDF Full-text (1089 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A crude methanolic extract of the Indonesian sponge Clathria bulbotoxa showed a potent cytotoxic activity against the human epidermoid carcinoma A431 cells. An investigation of the active components led to the isolation of three new compounds named crambescidins 345 (1), 361
[...] Read more.
A crude methanolic extract of the Indonesian sponge Clathria bulbotoxa showed a potent cytotoxic activity against the human epidermoid carcinoma A431 cells. An investigation of the active components led to the isolation of three new compounds named crambescidins 345 (1), 361 (2), and 373 (3), together with the known related metabolites crambescidins 359 (4), 657 (5), and 800 (6). The structures of the compounds were determined by spectroscopic analysis. These compounds 14 that possess a simple pentacyclic guanidine core exhibited moderate cytotoxicity against the A431 cells with the IC50 values of 7.0, 2.5, 0.94, and 3.1 μM, respectively, while the known compounds 5 and 6 that possess a long aliphatic side chain were found to be significantly cytotoxic. On the other hand, in an anti-oomycete activity test against the fungus-like plant pathogen Phytophthora capsici, 14 showed a higher activity than that of 5 and 6, suggesting that the long aliphatic side chain plays a significant role for cytotoxicity, but is not effective or suppressive for anti-oomycete activity. Full article
Figures

Graphical abstract

Open AccessArticle Conversion of Squid Pens to Chitosanases and Proteases via Paenibacillus sp. TKU042
Mar. Drugs 2018, 16(3), 83; https://doi.org/10.3390/md16030083
Received: 10 February 2018 / Revised: 26 February 2018 / Accepted: 6 March 2018 / Published: 8 March 2018
PDF Full-text (963 KB) | HTML Full-text | XML Full-text
Abstract
Chitosanases and proteases have received much attention due to their wide range of applications. Four kinds of chitinous materials, squid pens, shrimp heads, demineralized shrimp shells and demineralized crab shells, were used as the sole carbon and nitrogen (C/N) source to produce chitosanases,
[...] Read more.
Chitosanases and proteases have received much attention due to their wide range of applications. Four kinds of chitinous materials, squid pens, shrimp heads, demineralized shrimp shells and demineralized crab shells, were used as the sole carbon and nitrogen (C/N) source to produce chitosanases, proteases and α-glucosidase inhibitors (αGI) by four different strains of Paenibacillus. Chitosanase productivity was highest in the culture supernatants using squid pens as the sole C/N source. The maximum chitosanase activity of fermented squid pens (0.759 U/mL) was compared to that of fermented shrimp heads (0.397 U/mL), demineralized shrimp shells (0.201 U/mL) and demineralized crab shells (0.216 U/mL). A squid pen concentration of 0.5% was suitable for chitosanase, protease and αGI production via Paenibacillus sp. TKU042. Multi-purification, including ethanol precipitation and column chromatography of Macro-Prep High S as well as Macro-Prep DEAE (diethylaminoethyl), led to the isolation of Paenibacillus sp. TKU042 chitosanase and protease with molecular weights of 70 and 35 kDa, respectively. For comparison, 16 chitinolytic bacteria, including strains of Paenibacillus, were investigated for the production of chitinase, exochitinase, chitosanase, protease and αGI using two kinds of chitinous sources. Full article
(This article belongs to the Special Issue Bioconversion of Marine Resources)
Figures

Graphical abstract

Open AccessArticle Oligo-Porphyran Ameliorates Neurobehavioral Deficits in Parkinsonian Mice by Regulating the PI3K/Akt/Bcl-2 Pathway
Mar. Drugs 2018, 16(3), 82; https://doi.org/10.3390/md16030082
Received: 3 January 2018 / Revised: 21 February 2018 / Accepted: 2 March 2018 / Published: 6 March 2018
PDF Full-text (4920 KB) | HTML Full-text | XML Full-text
Abstract
Parkinson’s disease (PD) is a neurodegenerative movement disorder that is caused by a selective loss of dopaminergic neurons. Current PD treatments provide symptomatic relief but do not prevent or decelerate disease progression. Previous studies have suggested that acetylated and phosphorylated porphyran, derived from
[...] Read more.
Parkinson’s disease (PD) is a neurodegenerative movement disorder that is caused by a selective loss of dopaminergic neurons. Current PD treatments provide symptomatic relief but do not prevent or decelerate disease progression. Previous studies have suggested that acetylated and phosphorylated porphyran, derived from Porphyra, produces a neuroprotective effect against 6-OHDA-induced damage. Due to its antioxidant and neuroprotective potential, this study evaluates whether oligo-porphyran (OP) could be beneficial in an experimental model of PD in mice. The drug 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was intraperitoneally injected (20 mg/kg body weight) for seven days to simulate PD, followed by OP administration. We found that the behavioral deficits in spontaneous motor activity, latency to descend in a pole test, and suspension in a traction test were ameliorated, and excessive dopamine (DA) metabolism was suppressed after OP treatment. Additionally, we found that OP protected dopaminergic neurons by preventing MPTP-induced decreases in dopaminergic transporter and tyrosine hydroxylase protein levels. We speculated whether OP regulates a signaling pathway that affects the behavioral changes seen in PD mice. In this study, the PI3K/Akt/Bcl-2 pathway was detected. Our results demonstrate that OP increased the phosphorylation of PI3K/Akt/GSK-3β and inhibited the activation of caspase-3 and poly (ADP-ribose) polymerase, with changes in the Bax/Bcl-2 ratio. These results showed that OP might promote DA neuron survival in vivo by regulating the PI3K/Akt/Bcl-2 pathway, thereby ameliorating the neurobehavioral deficits in a PD mouse model and suggesting OP as a neuroprotective treatment for PD. Full article
(This article belongs to the Special Issue Marine Compounds in Neurodegenerative Diseases)
Figures

Graphical abstract

Open AccessArticle Preliminary Results on the Evaluation of the Occurrence of Tetrodotoxin Associated to Marine Vibrio spp. in Bivalves from the Galician Rias (Northwest of Spain)
Mar. Drugs 2018, 16(3), 81; https://doi.org/10.3390/md16030081
Received: 8 January 2018 / Revised: 23 February 2018 / Accepted: 1 March 2018 / Published: 6 March 2018
PDF Full-text (910 KB) | HTML Full-text | XML Full-text
Abstract
Tetrodotoxins (TTX) are a potent group of natural neurotoxins putatively produced by symbiotic microorganisms and affecting the aquatic environment. These neurotoxins have been recently found in some species of bivalves and gastropods along the European Coasts (Greece, UK, and The Netherlands) linked to
[...] Read more.
Tetrodotoxins (TTX) are a potent group of natural neurotoxins putatively produced by symbiotic microorganisms and affecting the aquatic environment. These neurotoxins have been recently found in some species of bivalves and gastropods along the European Coasts (Greece, UK, and The Netherlands) linked to the presence of high concentrations of Vibrio, in particular Vibrio parahaemolyticus. This study is focused on the evaluation of the presence of Vibrio species and TTX in bivalves (mussels, oysters, cockles, clams, scallops, and razor clams) from Galician Rias (northwest of Spain). The detection and isolation of the major Vibrio spp. and other enterobacterial populations have been carried out with the aim of screening for the presence of the pathways genes, poliketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS) possibly involved in the biosynthesis of these toxins. Samples containing Vibrio spp. were analyzed by biochemical (API20E-galery) and genetic tests (PCR-RT). These samples were then screened for TTX toxicity by a neuroblastoma cell-based assay (N2a) and the presence of TTX was further confirmed by LC-MS/MS. TTX was detected in two infaunal samples. This is the first confirmation of the presence of TTX in bivalve molluscs from the Galician Rias. Full article
(This article belongs to the Special Issue Tetrodotoxin)
Figures

Figure 1

Open AccessArticle Molecular Characterization of a Novel N-Acetylneuraminate Lyase from a Deep-Sea Symbiotic Mycoplasma
Mar. Drugs 2018, 16(3), 80; https://doi.org/10.3390/md16030080
Received: 31 January 2018 / Revised: 19 February 2018 / Accepted: 26 February 2018 / Published: 5 March 2018
Cited by 1 | PDF Full-text (2665 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
N-acetylneuraminic acid (Neu5Ac) based novel pharmaceutical agents and diagnostic reagents are highly required in medical fields. However, N-acetylneuraminate lyase(NAL)for Neu5Ac synthesis is not applicable for industry due to its low catalytic efficiency. In this study, we biochemically characterized a deep-sea NAL
[...] Read more.
N-acetylneuraminic acid (Neu5Ac) based novel pharmaceutical agents and diagnostic reagents are highly required in medical fields. However, N-acetylneuraminate lyase(NAL)for Neu5Ac synthesis is not applicable for industry due to its low catalytic efficiency. In this study, we biochemically characterized a deep-sea NAL enzyme (abbreviated form: MyNal) from a symbiotic Mycoplasma inhabiting the stomach of a deep-sea isopod, Bathynomus jamesi. Enzyme kinetic studies of MyNal showed that it exhibited a very low Km for both cleavage and synthesis activities compared to previously described NALs. Though it favors the cleavage process, MyNal out-competes the known NALs with respect to the efficiency of Neu5Ac synthesis and exhibits the highest kcat/Km values. High expression levels of recombinant MyNal could be achieved (9.56 mol L−1 culture) with a stable activity in a wide pH (5.0–9.0) and temperature (40–60 °C) range. All these features indicated that the deep-sea NAL has potential in the industrial production of Neu5Ac. Furthermore, we found that the amino acid 189 of MyNal (equivalent to Phe190 in Escherichia coli NAL), located in the sugar-binding domain, GX189DE, was also involved in conferring its enzymatic features. Therefore, the results of this study improved our understanding of the NALs from different environments and provided a model for protein engineering of NAL for biosynthesis of Neu5Ac. Full article
(This article belongs to the Special Issue Marine Natural Products from Symbiotic Ecosystems)
Figures

Figure 1

Open AccessReview Collagens of Poriferan Origin
Mar. Drugs 2018, 16(3), 79; https://doi.org/10.3390/md16030079
Received: 30 December 2017 / Revised: 3 February 2018 / Accepted: 28 February 2018 / Published: 3 March 2018
Cited by 4 | PDF Full-text (4914 KB) | HTML Full-text | XML Full-text
Abstract
The biosynthesis, structural diversity, and functionality of collagens of sponge origin are still paradigms and causes of scientific controversy. This review has the ambitious goal of providing thorough and comprehensive coverage of poriferan collagens as a multifaceted topic with intriguing hypotheses and numerous
[...] Read more.
The biosynthesis, structural diversity, and functionality of collagens of sponge origin are still paradigms and causes of scientific controversy. This review has the ambitious goal of providing thorough and comprehensive coverage of poriferan collagens as a multifaceted topic with intriguing hypotheses and numerous challenging open questions. The structural diversity, chemistry, and biochemistry of collagens in sponges are analyzed and discussed here. Special attention is paid to spongins, collagen IV-related proteins, fibrillar collagens from demosponges, and collagens from glass sponge skeletal structures. The review also focuses on prospects and trends in applications of sponge collagens for technology, materials science and biomedicine. Full article
(This article belongs to the Special Issue Collagen from Marine Biological Source and Medical Applications)
Figures

Figure 1

Open AccessArticle Microginins from a Microcystis sp. Bloom Material Collected from the Kishon Reservoir, Israel
Mar. Drugs 2018, 16(3), 78; https://doi.org/10.3390/md16030078
Received: 4 January 2018 / Revised: 25 February 2018 / Accepted: 28 February 2018 / Published: 2 March 2018
PDF Full-text (739 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
During blooms, cyanobacteria produce diverse modified peptides. Among these are the microginins, which inhibit zinc-containing metalloproteases. Ten microginins, microginins KR767 (1), KR801(2), KR835 (3), KR785 (4), KR604 (5), KR638 (6), KR781
[...] Read more.
During blooms, cyanobacteria produce diverse modified peptides. Among these are the microginins, which inhibit zinc-containing metalloproteases. Ten microginins, microginins KR767 (1), KR801(2), KR835 (3), KR785 (4), KR604 (5), KR638 (6), KR781 (7), KR815 (8), FR3 (9), and FR4 (10), were isolated from the extract of a bloom material of Microcystis sp. (IL-405) collected from the Kishon Reservoir, Israel in the fall of 2009. The structures of the pure compounds were elucidated using 1D and 2D NMR techniques and high-resolution mass spectrometry. The absolute configuration of the chiral centers of the amino acids were determined by Marfey’s and advance Marfey’s methods and by comparison of 1H and 13C NMR chemical shifts of the Ahda derivatives with those of known microginins. These microginins differ in sequence and absolute configuration of the chiral centers of the Ahda moieties and by N-methylation of the Ahda amine group and extent of chlorination of the Ahda terminal methyl group. The compounds were evaluated for inhibition of the zinc metalloprotease, aminopeptidase M, and exhibited low- to sub-nanomolar half maximal inhibitory concentration (IC50) values. Full article
Figures

Graphical abstract

Open AccessArticle ATG5 Promotes Death Signaling in Response to the Cyclic Depsipeptides Coibamide A and Apratoxin A
Mar. Drugs 2018, 16(3), 77; https://doi.org/10.3390/md16030077
Received: 14 December 2017 / Revised: 17 February 2018 / Accepted: 23 February 2018 / Published: 1 March 2018
Cited by 1 | PDF Full-text (4926 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Our understanding of autophagy and lysosomal function has been greatly enhanced by the discovery of natural product structures that can serve as chemical probes to reveal new patterns of signal transduction in cells. Coibamide A is a cytotoxic marine natural product that induces
[...] Read more.
Our understanding of autophagy and lysosomal function has been greatly enhanced by the discovery of natural product structures that can serve as chemical probes to reveal new patterns of signal transduction in cells. Coibamide A is a cytotoxic marine natural product that induces mTOR-independent autophagy as an adaptive stress response that precedes cell death. Autophagy-related (ATG) protein 5 (ATG5) is required for coibamide-induced autophagy but not required for coibamide-induced apoptosis. Using wild-type and autophagy-deficient mouse embryonic fibroblasts (MEFs) we demonstrate that coibamide-induced toxicity is delayed in ATG5−/− cells relative to ATG5+/+ cells. Time-dependent changes in annexin V staining, membrane integrity, metabolic capacity and caspase activation indicated that MEFs with a functional autophagy pathway are more sensitive to coibamide A. This pattern could be distinguished from autophagy modulators that induce acute ER stress (thapsigargin, tunicamycin), ATP depletion (oligomycin A) or mTORC1 inhibition (rapamycin), but was shared with the Sec61 inhibitor apratoxin A. Coibamide- or apratoxin-induced cell stress was further distinguished from the action of thapsigargin by a pattern of early LC3-II accumulation in the absence of CHOP or BiP expression. Time-dependent changes in ATG5-ATG12, PARP1 and caspase-3 expression patterns were consistent with the conversion of ATG5 to a pro-death signal in response to both compounds. Full article
(This article belongs to the Special Issue Marine Compounds as Modulators of Autophagy and Lysosomal Activity)
Figures

Graphical abstract

Open AccessArticle Comparative Analysis of Culture Conditions for the Optimization of Carotenoid Production in Several Strains of the Picoeukaryote Ostreococcus
Mar. Drugs 2018, 16(3), 76; https://doi.org/10.3390/md16030076
Received: 29 January 2018 / Revised: 16 February 2018 / Accepted: 16 February 2018 / Published: 28 February 2018
PDF Full-text (1484 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Microalgae are promising sources for the sustainable production of compounds of interest for biotechnologies. Compared to higher plants, microalgae have a faster growth rate and can be grown in industrial photobioreactors. The microalgae biomass contains specific metabolites of high added value for biotechnology
[...] Read more.
Microalgae are promising sources for the sustainable production of compounds of interest for biotechnologies. Compared to higher plants, microalgae have a faster growth rate and can be grown in industrial photobioreactors. The microalgae biomass contains specific metabolites of high added value for biotechnology such as lipids, polysaccharides or carotenoid pigments. Studying carotenogenesis is important for deciphering the mechanisms of adaptation to stress tolerance as well as for biotechnological production. In recent years, the picoeukaryote Ostreococcus tauri has emerged as a model organism thanks to the development of powerful genetic tools. Several strains of Ostreococcus isolated from different environments have been characterized with respect to light response or iron requirement. We have compared the carotenoid contents and growth rates of strains of Ostreococcus (OTTH595, RCC802 and RCC809) under a wide range of light, salinity and temperature conditions. Carotenoid profiles and productivities varied in a strain-specific and stress-dependent manner. Our results also illustrate that phylogenetically related microalgal strains originating from different ecological niches present specific interests for the production of specific molecules under controlled culture conditions. Full article
(This article belongs to the Special Issue Marine Microalgae)
Figures

Figure 1

Open AccessArticle Briaviolides K–N, New Briarane-Type Diterpenoids from Cultured Octocoral Briareum violaceum
Mar. Drugs 2018, 16(3), 75; https://doi.org/10.3390/md16030075
Received: 19 December 2017 / Revised: 1 February 2018 / Accepted: 23 February 2018 / Published: 27 February 2018
Cited by 1 | PDF Full-text (3491 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Four new briarane diterpenoids, briaviolides K–N (14), have been obtained from the cultured-type octocoral Briareum violaceum. Using a spectroscopic approach, the structures of briaranes 14 were identified. This study employed an in vitro model of lipopolysaccharide
[...] Read more.
Four new briarane diterpenoids, briaviolides K–N (14), have been obtained from the cultured-type octocoral Briareum violaceum. Using a spectroscopic approach, the structures of briaranes 14 were identified. This study employed an in vitro model of lipopolysaccharide (LPS)-induced inflammation in the murine macrophage RAW 264.7 cell line, and found that among the four briaranes, briarane 2 possessed anti-inflammatory activity against inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expressions in cells. In addition, principal component analysis using the chemical global positioning system (ChemGPS) for natural products (ChemGPS-NP) was employed in order to analyze the structure-activity relationship (SAR), and the results indicated that the ring conformation of the compound has a leading role in suppressing the expressions of pro-inflammatory iNOS and COX-2 proteins in macrophages. Full article
(This article belongs to the Special Issue Natural Products from Coral Reef Organisms)
Figures

Graphical abstract

Back to Top