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Mar. Drugs, Volume 15, Issue 4 (April 2017)

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Cover Story In this review, we have attempted to describe all of the antibody–drug conjugates using a [...] Read more.
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Open AccessArticle Establishing the Secondary Metabolite Profile of the Marine Fungus: Tolypocladium geodes sp. MF458 and Subsequent Optimisation of Bioactive Secondary Metabolite Production
Mar. Drugs 2017, 15(4), 84; doi:10.3390/md15040084
Received: 23 December 2016 / Revised: 7 March 2017 / Accepted: 12 March 2017 / Published: 23 March 2017
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Abstract
As part of an international research project, the marine fungal strain collection of the Helmholtz Centre for Ocean Research (GEOMAR) research centre was analysed for secondary metabolite profiles associated with anticancer activity. Strain MF458 was identified as Tolypocladium geodes, by internal transcribed
[...] Read more.
As part of an international research project, the marine fungal strain collection of the Helmholtz Centre for Ocean Research (GEOMAR) research centre was analysed for secondary metabolite profiles associated with anticancer activity. Strain MF458 was identified as Tolypocladium geodes, by internal transcribed spacer region (ITS) sequence similarity and its natural product production profile. By using five different media in two conditions and two time points, we were able to identify eight natural products produced by MF458. As well as cyclosporin A (1), efrapeptin D (2), pyridoxatin (3), terricolin A (4), malettinins B and E (5 and 6), and tolypocladenols A1/A2 (8), we identified a new secondary metabolite which we termed tolypocladenol C (7). All compounds were analysed for their anticancer potential using a selection of the NCI60 cancer cell line panel, with malettinins B and E (5 and 6) being the most promising candidates. In order to obtain sufficient quantities of these compounds to start preclinical development, their production was transferred from a static flask culture to a stirred tank reactor, and fermentation medium development resulted in a nearly eight-fold increase in compound production. The strain MF458 is therefore a producer of a number of interesting and new secondary metabolites and their production levels can be readily improved to achieve higher yields. Full article
(This article belongs to the Special Issue Marine Fungal Natural Products)
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Open AccessArticle Biscembranoids and Cembranoids from the Soft Coral Sarcophyton elegans
Mar. Drugs 2017, 15(4), 85; doi:10.3390/md15040085
Received: 13 February 2017 / Revised: 16 March 2017 / Accepted: 20 March 2017 / Published: 23 March 2017
Cited by 1 | PDF Full-text (3533 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two novel biscembranoids, sarelengans A and B (1 and 2), five new cembranoids, sarelengans C–G (37), along with two known cembranoids (8 and 9) were isolated from the South China Sea soft coral Sarcophyton elegans
[...] Read more.
Two novel biscembranoids, sarelengans A and B (1 and 2), five new cembranoids, sarelengans C–G (37), along with two known cembranoids (8 and 9) were isolated from the South China Sea soft coral Sarcophyton elegans. Their structures were determined by spectroscopic and chemical methods, and those of 1, 4, 5, and 6 were confirmed by single crystal X-ray diffraction. Compounds 1 and 2 represent the first example of biscembranoids featuring a trans-fused A/B-ring conjunction between the two cembranoid units. Their unique structures may shed light on an unusual biosynthetic pathway involving a cembranoid-∆8 rather than the normal cembranoid-∆1 unit in the endo-Diels-Alder cycloaddition. Compounds 2 and 3 exhibited potential inhibitory effects on nitric oxide production in RAW 264.7 macrophages, with IC50 values being at 18.2 and 32.5 μM, respectively. Full article
(This article belongs to the collection Bioactive Compounds from Marine Invertebrates)
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Open AccessCommunication Marine Cyclic Guanidine Alkaloids Monanchomycalin B and Urupocidin A Act as Inhibitors of TRPV1, TRPV2 and TRPV3, but not TRPA1 Receptors
Mar. Drugs 2017, 15(4), 87; doi:10.3390/md15040087
Received: 16 January 2017 / Revised: 28 February 2017 / Accepted: 20 March 2017 / Published: 23 March 2017
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Abstract
Marine sponges contain a variety of low-molecular-weight compounds including guanidine alkaloids possessing different biological activities. Monanchomycalin B and urupocidin A were isolated from the marine sponge Monanchora pulchra. We found that they act as inhibitors of the TRPV1, TRPV2, and TRPV3 channels, but
[...] Read more.
Marine sponges contain a variety of low-molecular-weight compounds including guanidine alkaloids possessing different biological activities. Monanchomycalin B and urupocidin A were isolated from the marine sponge Monanchora pulchra. We found that they act as inhibitors of the TRPV1, TRPV2, and TRPV3 channels, but are inactive against the TRPA1 receptor. Monanchomycalin B is the most active among all published marine alkaloids (EC50 6.02, 2.84, and 3.25 μM for TRPV1, TRPV2, and TRPV3, correspondingly). Moreover, monanchomycalin B and urupocidin A are the first samples of marine alkaloids affecting the TRPV2 receptor. Two semi-synthetic urupocidin A derivatives were also obtained and tested against TRP (Transient Receptor Potential) receptors that allowed us to collect some data concerning the structure-activity relationship in this series of compounds. We showed that the removal of one of three side chains or double bonds in the other side chains in urupocidin A led to a decrease of the inhibitory activities. New ligands specific to the TRPV subfamily may be useful for the design of medicines as in the study of TRP channels biology. Full article
(This article belongs to the collection Bioactive Compounds from Marine Invertebrates)
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Open AccessArticle Anti-Obesity and Anti-Diabetic Effect of Neoagarooligosaccharides on High-Fat Diet-Induced Obesity in Mice
Mar. Drugs 2017, 15(4), 90; doi:10.3390/md15040090
Received: 9 December 2016 / Revised: 9 March 2017 / Accepted: 16 March 2017 / Published: 23 March 2017
Cited by 1 | PDF Full-text (2156 KB) | HTML Full-text | XML Full-text
Abstract
Neoagarooligosaccharides (NAOs), mainly comprising neoagarotetraose and neoagarohexaose, were prepared by hydrolyzing agar with β-agarase DagA from Streptomyces coelicolor, and the anti-obesity and anti-diabetic effects of NAOs on high-fat diet (HFD)-induced obesity in mice were investigated after NAOs-supplementation for 64 days. Compared to the
[...] Read more.
Neoagarooligosaccharides (NAOs), mainly comprising neoagarotetraose and neoagarohexaose, were prepared by hydrolyzing agar with β-agarase DagA from Streptomyces coelicolor, and the anti-obesity and anti-diabetic effects of NAOs on high-fat diet (HFD)-induced obesity in mice were investigated after NAOs-supplementation for 64 days. Compared to the HFD group, the HFD-0.5 group that was fed with HFD + NAOs (0.5%, w/w) showed remarkable reduction of 36% for body weight gain and 37% for food efficiency ratios without abnormal clinical signs. Furthermore, fat accumulation in the liver and development of macrovesicular steatosis induced by HFD in the HFD-0.5 group were recovered nearly to the levels found in the normal diet (ND) group. NAOs intake could also effectively reduce the size (area) of adipocytes and tissue weight gain in the perirenal and epididymal adipose tissues. The increased concentrations of total cholesterol, triglyceride, and free fatty acid in serum of the HFD group were also markedly ameliorated to the levels found in serum of the ND group after NAOs-intake in a dose dependent manner. In addition, insulin resistance and glucose intolerance induced by HFD were distinctly improved, and adiponectin concentration in the blood was notably increased. All these results strongly suggest that intake of NAOs can effectively suppress obesity and obesity-related metabolic syndromes, such as hyperlipidemia, steatosis, insulin resistance, and glucose intolerance, by inducing production of adiponectin in the HFD-induced obese mice. Full article
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Open AccessArticle Preparation, Characterization and Properties of Alginate/Poly(γ-glutamic acid) Composite Microparticles
Mar. Drugs 2017, 15(4), 91; doi:10.3390/md15040091
Received: 27 November 2016 / Revised: 12 March 2017 / Accepted: 20 March 2017 / Published: 11 April 2017
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Abstract
Alginate (Alg) is a renewable polymer with excellent hemostatic properties and biocapability and is widely used for hemostatic wound dressing. However, the swelling properties of alginate-based wound dressings need to be promoted to meet the requirements of wider application. Poly(γ-glutamic acid)
[...] Read more.
Alginate (Alg) is a renewable polymer with excellent hemostatic properties and biocapability and is widely used for hemostatic wound dressing. However, the swelling properties of alginate-based wound dressings need to be promoted to meet the requirements of wider application. Poly(γ-glutamic acid) (PGA) is a natural polymer with high hydrophility. In the current study, novel Alg/PGA composite microparticles with double network structure were prepared by the emulsification/internal gelation method. It was found from the structure characterization that a double network structure was formed in the composite microparticles due to the ion chelation interaction between Ca2+ and the carboxylate groups of Alg and PGA and the electrostatic interaction between the secondary amine group of PGA and the carboxylate groups of Alg and PGA. The swelling behavior of the composite microparticles was significantly improved due to the high hydrophility of PGA. Influences of the preparing conditions on the swelling behavior of the composites were investigated. The porous microparticles could be formed while compositing of PGA. Thermal stability was studied by thermogravimetric analysis method. Moreover, in vitro cytocompatibility test of microparticles exhibited good biocompatibility with L929 cells. All results indicated that such Alg/PGA composite microparticles are a promising candidate in the field of wound dressing for hemostasis or rapid removal of exudates. Full article
(This article belongs to the collection Marine Polysaccharides)
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Open AccessArticle Degradation of Marine Algae-Derived Carbohydrates by Bacteroidetes Isolated from Human Gut Microbiota
Mar. Drugs 2017, 15(4), 92; doi:10.3390/md15040092
Received: 2 January 2017 / Revised: 14 March 2017 / Accepted: 20 March 2017 / Published: 24 March 2017
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Abstract
Carrageenan, agarose, and alginate are algae-derived undigested polysaccharides that have been used as food additives for hundreds of years. Fermentation of dietary carbohydrates of our food in the lower gut of humans is a critical process for the function and integrity of both
[...] Read more.
Carrageenan, agarose, and alginate are algae-derived undigested polysaccharides that have been used as food additives for hundreds of years. Fermentation of dietary carbohydrates of our food in the lower gut of humans is a critical process for the function and integrity of both the bacterial community and host cells. However, little is known about the fermentation of these three kinds of seaweed carbohydrates by human gut microbiota. Here, the degradation characteristics of carrageenan, agarose, alginate, and their oligosaccharides, by Bacteroides xylanisolvens, Bacteroides ovatus, and Bacteroides uniforms, isolated from human gut microbiota, are studied. Full article
(This article belongs to the collection Marine Polysaccharides)
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Open AccessArticle Outdoor Cultivation of Marine Diatoms for Year-Round Production of Biofuels
Mar. Drugs 2017, 15(4), 94; doi:10.3390/md15040094
Received: 31 January 2017 / Revised: 15 March 2017 / Accepted: 22 March 2017 / Published: 25 March 2017
Cited by 1 | PDF Full-text (1554 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Biofuel production using microalgae is believed to have the advantage of continuous year-round production over crop plants, which have strong seasonality. However, actual year-round production of microalgal lipids using outdoor mass cultivation has rarely been demonstrated. In our previous study, it was demonstrated
[...] Read more.
Biofuel production using microalgae is believed to have the advantage of continuous year-round production over crop plants, which have strong seasonality. However, actual year-round production of microalgal lipids using outdoor mass cultivation has rarely been demonstrated. In our previous study, it was demonstrated that the oleaginous diatom, Fistulifera solaris, was culturable in outdoor bioreactors from spring to autumn, whereas biomass and lipid production in winter failed because F. solaris did not grow below 15 °C. Therefore, another candidate strain that is culturable in winter is required. In this study, a cold-tolerant diatom, Mayamaea sp. JPCC CTDA0820, was selected as a promising candidate for biofuel production in winter. Laboratory-scale characterization revealed that this diatom was culturable at temperatures as low as 10 °C. Subsequently, F. solaris (April–October) and Mayamaea sp. JPCC CTDA0820 (November–March) were cultured in outdoor open-pond bioreactors, wherein year-round production of diatom lipids was successfully demonstrated. The maximal values of areal productivities of biomass and lipids reached to 9.79 and 1.80 g/(m2 day) for F. solaris, and 8.62 and 0.92 g/(m2 day) for Mayamaea sp. JPCC CTDA0820, respectively. With the combined use of these two diatom species, stable year-round production of microalgal lipids became possible. Full article
(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology II 2016)
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Open AccessFeature PaperArticle A Place to Call Home: An Analysis of the Bacterial Communities in Two Tethya rubra Samaai and Gibbons 2005 Populations in Algoa Bay, South Africa
Mar. Drugs 2017, 15(4), 95; doi:10.3390/md15040095
Received: 31 January 2017 / Revised: 8 March 2017 / Accepted: 16 March 2017 / Published: 25 March 2017
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Abstract
Sponges are important sources of bioactive secondary metabolites. These compounds are frequently synthesized by bacterial symbionts, which may be recruited from the surrounding seawater or transferred to the sponge progeny by the parent. In this study, we investigated the bacterial communities associated with
[...] Read more.
Sponges are important sources of bioactive secondary metabolites. These compounds are frequently synthesized by bacterial symbionts, which may be recruited from the surrounding seawater or transferred to the sponge progeny by the parent. In this study, we investigated the bacterial communities associated with the sponge Tethya rubra Samaai and Gibbons 2005. Sponge specimens were collected from Evans Peak and RIY Banks reefs in Algoa Bay, South Africa and taxonomically identified by spicule analysis and molecular barcoding. Crude chemical extracts generated from individual sponges were profiled by ultraviolet high performance liquid chromatography (UV-HPLC) and subjected to bioactivity assays in mammalian cells. Next-generation sequencing analysis of 16S rRNA gene sequences was used to characterize sponge-associated bacterial communities. T. rubra sponges collected from the two locations were morphologically and genetically indistinguishable. Chemical extracts from sponges collected at RIY banks showed mild inhibition of the metabolic activity of mammalian cells and their UV-HPLC profiles were distinct from those of sponges collected at Evans Peak. Similarly, the bacterial communities associated with sponges from the two locations were distinct with evidence of vertical transmission of symbionts from the sponge parent to its embryos. We conclude that these distinct bacterial communities may be responsible for the differences observed in the chemical profiles of the two Algoa Bay T. rubra Samaai and Gibbons 2005 populations. Full article
(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology II 2016)
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Open AccessArticle Variation Quality and Kinetic Parameter of Commercial n-3 PUFA-Rich Oil during Oxidation via Rancimat
Mar. Drugs 2017, 15(4), 97; doi:10.3390/md15040097
Received: 13 January 2017 / Revised: 17 March 2017 / Accepted: 20 March 2017 / Published: 28 March 2017
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Abstract
Different biological sources of n-3 polyunsaturated fatty acids (n-3 PUFA) in mainstream commercial products include algae and fish. Lipid oxidation in n-3 PUFA-rich oil is the most important cause of its deterioration. We investigated the kinetic parameters of n
[...] Read more.
Different biological sources of n-3 polyunsaturated fatty acids (n-3 PUFA) in mainstream commercial products include algae and fish. Lipid oxidation in n-3 PUFA-rich oil is the most important cause of its deterioration. We investigated the kinetic parameters of n-3 PUFA-rich oil during oxidation via Rancimat (at a temperature range of 70~100 °C). This was done on the basis of the Arrhenius equation, which indicates that the activation energies (Ea) for oxidative stability are 82.84–96.98 KJ/mol. The chemical substrates of different oxidative levels resulting from oxidation via Rancimat at 80 °C were evaluated. At the initiation of oxidation, the tocopherols in the oil degraded very quickly, resulting in diminished protection against further oxidation. Then, the degradation of the fatty acids with n-3 PUFA-rich oil was evident because of decreased levels of PUFA along with increased levels of saturated fatty acids (SFA). The quality deterioration from n-3 PUFA-rich oil at the various oxidative levels was analyzed chemometrically. The anisidine value (p-AV, r: 0.92) and total oxidation value (TOTOX, r: 0.91) exhibited a good linear relationship in a principal component analysis (PCA), while oxidative change and a significant quality change to the induction period (IP) were detected through an agglomerative hierarchical cluster (AHC) analysis. Full article
(This article belongs to the Special Issue Marine Lipids 2017)
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Open AccessFeature PaperArticle Another Look at Pyrroloiminoquinone Alkaloids—Perspectives on Their Therapeutic Potential from Known Structures and Semisynthetic Analogues
Mar. Drugs 2017, 15(4), 98; doi:10.3390/md15040098
Received: 26 January 2017 / Revised: 15 March 2017 / Accepted: 27 March 2017 / Published: 29 March 2017
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Abstract
This study began with the goal of identifying constituents from Zyzzya fuliginosa extracts that showed selectivity in our primary cytotoxicity screen against the PANC-1 tumor cell line. During the course of this project, which focused on six Z. fuliginosa samples collected from
[...] Read more.
This study began with the goal of identifying constituents from Zyzzya fuliginosa extracts that showed selectivity in our primary cytotoxicity screen against the PANC-1 tumor cell line. During the course of this project, which focused on six Z. fuliginosa samples collected from various regions of the Indo-Pacific, known compounds were obtained consisting of nine makaluvamine and three damirone analogues. Four new acetylated derivatives were also prepared. High-accuracy electrospray ionization mass spectrometry (HAESI-MS) m/z ions produced through MS2 runs were obtained and interpreted to provide a rapid way for dereplicating isomers containing a pyrrolo[4,3,2-de]quinoline core. In vitro human pancreas/duct epithelioid carcinoma (PANC-1) cell line IC50 data was obtained for 16 compounds and two therapeutic standards. These results along with data gleaned from the literature provided useful structure activity relationship conclusions. Three structural motifs proved to be important in maximizing potency against PANC-1: (i) conjugation within the core of the ABC-ring; (ii) the presence of a positive charge in the C-ring; and (iii) inclusion of a 4-ethyl phenol or 4-ethyl phenol acetate substituent off the B-ring. Two compounds, makaluvamine J (9) and 15-O-acetyl makaluvamine J (15), contained all three of these frameworks and exhibited the best potency with IC50 values of 54 nM and 81 nM, respectively. These two most potent analogs were then tested against the OVCAR-5 cell line and the presence of the acetyl group increased the potency 14-fold from that of 9 whose IC50 = 120 nM vs. that of 15 having IC50 = 8.6 nM. Full article
(This article belongs to the Special Issue Marine Drugs as Antitumour Agents 2017)
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Open AccessArticle Characterization and Potential Antitumor Activity of Polysaccharide from Gracilariopsis lemaneiformis
Mar. Drugs 2017, 15(4), 100; doi:10.3390/md15040100
Received: 8 January 2017 / Revised: 21 March 2017 / Accepted: 23 March 2017 / Published: 29 March 2017
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Abstract
Substances with valuable antitumor properties have been identified in many marine algae, including an edible polysaccharide from the marine alga Gracilariopsis lemaneiformis (PGL). We previously reported transcriptome profiling data showing that PGL induced transcriptional alterations generate anti-lung cancer activity. To identify how PGL
[...] Read more.
Substances with valuable antitumor properties have been identified in many marine algae, including an edible polysaccharide from the marine alga Gracilariopsis lemaneiformis (PGL). We previously reported transcriptome profiling data showing that PGL induced transcriptional alterations generate anti-lung cancer activity. To identify how PGL is detrimental to tumors, we purified PGL to characterize its chemical composition, molecular weight, and sugar and protein content and investigated its antitumor activity. We demonstrated that PGL exerted its antitumor activities by modulating cell viability, morphology, apoptosis, and the apoptosis-related Fas/FasL signaling pathway in the human lung cancer cell line A549, the gastric cancer cell line MKN28, and the mouse melanoma cell line B16. Our data provide the first evidence that PGL inhibits cell proliferation by inducing apoptosis, which is largely mediated by Fas/FasL in cancer cells, suggesting that PGL might be a novel therapeutic agent against cancer. Full article
(This article belongs to the Special Issue Marine Drugs as Antitumour Agents 2017)
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Open AccessArticle The Influence of Tetrodotoxin (TTX) on the Distribution and Chemical Coding of Caudal Mesenteric Ganglion (CaMG) Neurons Supplying the Porcine Urinary Bladder
Mar. Drugs 2017, 15(4), 101; doi:10.3390/md15040101
Received: 25 January 2017 / Revised: 23 March 2017 / Accepted: 27 March 2017 / Published: 30 March 2017
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Abstract
The treatment of micturition disorders creates a serious problem for urologists. Recently, new therapeutic agents, such as neurotoxins, are being considered for the therapy of urological patients. The present study investigated the chemical coding of caudal mesenteric ganglion (CaMG) neurons supplying the porcine
[...] Read more.
The treatment of micturition disorders creates a serious problem for urologists. Recently, new therapeutic agents, such as neurotoxins, are being considered for the therapy of urological patients. The present study investigated the chemical coding of caudal mesenteric ganglion (CaMG) neurons supplying the porcine urinary bladder after intravesical instillation of tetrodotoxin (TTX). The CaMG neurons were visualized with retrograde tracer Fast blue (FB) and their chemical profile was disclosed with double-labeling immunohistochemistry using antibodies against tyrosine hydroxylase (TH), neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), somatostatin (SOM), calbindin (CB), galanin (GAL) and neuronal nitric oxide synthase (nNOS). It was found that in both the control (n = 6) and TTX-treated pigs (n = 6), the vast majority (92.6% ± 3.4% and 88.8% ± 2%, respectively) of FB-positive (FB+) nerve cells were TH+. TTX instillation caused a decrease in the number of FB+/TH+ neurons immunopositive to NPY (88.9% ± 5.3% in the control animals vs. 10.6% ± 5.3% in TTX-treated pigs) or VIP (1.7% ± 0.6% vs. 0%), and an increase in the number of FB+/TH+ neurons immunoreactive to SOM (8.8% ± 1.6% vs. 39% ± 12.8%), CB (1.8% ± 0.7% vs. 12.6% ± 2.7%), GAL (1.7% ± 0.8% vs. 10.9% ± 2.6%) or nNOS (0% vs. 1.1% ± 0.3%). The present study is the first to suggest that TTX modifies the chemical coding of CaMG neurons supplying the porcine urinary bladder. Full article
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Open AccessArticle Marine Collagen Peptides from the Skin of Nile Tilapia (Oreochromis niloticus): Characterization and Wound Healing Evaluation
Mar. Drugs 2017, 15(4), 102; doi:10.3390/md15040102
Received: 19 February 2017 / Revised: 26 March 2017 / Accepted: 27 March 2017 / Published: 30 March 2017
Cited by 2 | PDF Full-text (4155 KB) | HTML Full-text | XML Full-text
Abstract
Burns can cause tremendous economic problems associated with irreparable harm to patients and their families. To characterize marine collagen peptides (MCPs) from the skin of Nile tilapia (Oreochromis niloticus), molecular weight distribution and amino acid composition of MCPs were determined, and
[...] Read more.
Burns can cause tremendous economic problems associated with irreparable harm to patients and their families. To characterize marine collagen peptides (MCPs) from the skin of Nile tilapia (Oreochromis niloticus), molecular weight distribution and amino acid composition of MCPs were determined, and Fourier transform infrared spectroscopy (FTIR) was used to analyze the chemical structure. Meanwhile, to evaluate the wound healing activity, in vitro and in vivo experiments were carried out. The results showed that MCPs prepared from the skin of Nile tilapia by composite enzymatic hydrolysis were composed of polypeptides with different molecular weights and the contents of polypeptides with molecular weights of less than 5 kDa accounted for 99.14%. From the amino acid composition, the majority of residues, accounting for over 58% of the total residues in MCPs, were hydrophilic. FTIR indicated that the main molecular conformations inside MCPs were random coil. In vitro scratch assay showed that there were significant effects on the scratch closure by the treatment of MCPs with the concentration of 50.0 μg/mL. In the experiments of deep partial-thickness scald wound in rabbits, MCPs could enhance the process of wound healing. Therefore, MCPs from the skin of Nile tilapia (O. niloticus) have promising applications in wound care. Full article
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Open AccessArticle Optimization of Bromelain-Aided Production of Angiotensin I-Converting Enzyme Inhibitory Hydrolysates from Stone Fish Using Response Surface Methodology
Mar. Drugs 2017, 15(4), 104; doi:10.3390/md15040104
Received: 8 November 2016 / Revised: 15 March 2017 / Accepted: 24 March 2017 / Published: 31 March 2017
Cited by 2 | PDF Full-text (1840 KB) | HTML Full-text | XML Full-text
Abstract
The stone fish is an under-utilized sea cucumber with many nutritional and ethno-medicinal values. This study aimed to establish the conditions for its optimum hydrolysis with bromelain to generate angiotensin I-converting enzyme (ACE)-inhibitory hydrolysates. Response surface methodology (RSM) based on a central composite
[...] Read more.
The stone fish is an under-utilized sea cucumber with many nutritional and ethno-medicinal values. This study aimed to establish the conditions for its optimum hydrolysis with bromelain to generate angiotensin I-converting enzyme (ACE)-inhibitory hydrolysates. Response surface methodology (RSM) based on a central composite design was used to model and optimize the degree of hydrolysis (DH) and ACE-inhibitory activity. Process conditions including pH (4–7), temperature (40–70 °C), enzyme/substrate (E/S) ratio (0.5%–2%) and time (30–360 min) were used. A pH of 7.0, temperature of 40 °C, E/S ratio of 2% and time of 240 min were determined using a response surface model as the optimum levels to obtain the maximum ACE-inhibitory activity of 84.26% at 44.59% degree of hydrolysis. Hence, RSM can serve as an effective approach in the design of experiments to improve the antihypertensive effect of stone fish hydrolysates, which can thus be used as a value-added ingredient for various applications in the functional foods industries. Full article
(This article belongs to the Special Issue Enzyme Inhibitors of Marine Origin)
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Open AccessArticle Fluorescent Property of Chitosan Oligomer and Its Application as a Metal Ion Sensor
Mar. Drugs 2017, 15(4), 105; doi:10.3390/md15040105
Received: 26 December 2016 / Revised: 13 March 2017 / Accepted: 29 March 2017 / Published: 4 April 2017
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Abstract
An aqueous solution was successfully prepared using a low-molecular-weight chitosan oligomer and FITC, and its structural and fluorescent properties were observed by using 1H NMR, 13C NMR, FT-IR, XRD, UV-Vis, and PL spectrometry. Its application as a metal ion sensor was
[...] Read more.
An aqueous solution was successfully prepared using a low-molecular-weight chitosan oligomer and FITC, and its structural and fluorescent properties were observed by using 1H NMR, 13C NMR, FT-IR, XRD, UV-Vis, and PL spectrometry. Its application as a metal ion sensor was also evaluated. The fluorescence in the water-soluble chitosan oligomer was a result of the carbamato anion (NHCOO-), and a synthesized FITC-labeled chitosan oligomer exhibited an effective detection effect for copper ion as well as energy transfer by the ion near FITC that caused a fluorescence decrease (quenching). The chitosan oligomer was confirmed to be applicable as a selective and sensitive colorimetric sensor to detect Cu2+. Full article
(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan II, 2017)
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Open AccessArticle The Effect of Phloroglucinol, A Component of Ecklonia cava Extract, on Hepatic Glucose Production
Mar. Drugs 2017, 15(4), 106; doi:10.3390/md15040106
Received: 2 February 2017 / Revised: 25 March 2017 / Accepted: 2 April 2017 / Published: 5 April 2017
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Abstract
Phloroglucinol is a phenolic compound that is one of the major compounds in Ecklonia cava (brown alga). It has many pharmacological activities, but its anti-diabetic effect is not yet fully explored. In this study, we investigated the effect of phloroglucinol on the control
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Phloroglucinol is a phenolic compound that is one of the major compounds in Ecklonia cava (brown alga). It has many pharmacological activities, but its anti-diabetic effect is not yet fully explored. In this study, we investigated the effect of phloroglucinol on the control of blood glucose levels and the regulation of hepatic glucose production. Phloroglucinol significantly improved glucose tolerance in male C57BL/6J mice fed a high fat diet (HFD) and inhibited glucose production in mouse primary hepatocytes. The expression of phosphoenol pyruvate carboxykinase (PEPCK) and glucose-6-phosphatase mRNA and protein (G6Pase), enzymes involved in gluconeogenesis, were inhibited in liver tissue from phloroglucinol-treated mice and in phloroglucinol-treated HepG2 cells. In addition, phloroglucinol treatment increased phosphorylated AMP-activated protein kinase (AMPK)α in HepG2 cells. Treatment with compound C, an AMPKα inhibitor, inhibited the increase of phosphorylated AMPKα and the decrease of PEPCK and G6Pase expression caused by phloroglucinol treatment. We conclude that phloroglucinol may inhibit hepatic gluconeogenesis via modulating the AMPKα signaling pathway, and thus lower blood glucose levels. Full article
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Open AccessArticle Pharmacophore-Based Virtual Screening of Novel Inhibitors and Docking Analysis for CYP51A from Penicillium italicum
Mar. Drugs 2017, 15(4), 107; doi:10.3390/md15040107
Received: 10 February 2017 / Revised: 24 March 2017 / Accepted: 30 March 2017 / Published: 5 April 2017
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Abstract
Sterol 14α-demethylases from Cytochrome P450 family (CYP51s) are essential enzymes in sterol biosynthesis and well-known as the target of antifungal drugs. The 3D structure of CYP51A from Penicillium italicum (PiCYP51A) was constructed through homology modeling based on the crystal structure of human CYP51A
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Sterol 14α-demethylases from Cytochrome P450 family (CYP51s) are essential enzymes in sterol biosynthesis and well-known as the target of antifungal drugs. The 3D structure of CYP51A from Penicillium italicum (PiCYP51A) was constructed through homology modeling based on the crystal structure of human CYP51A (PDB: 3LD6). Molecular dynamics (MD) simulation was operated to relax the initial model and followed by quality assessment using PROCHECK program. On the basis of the docking information on the currently available CYP51s with the patent demethylase inhibitors (DMIs), pharmacophore-based virtual screening combined with docking analysis was performed to pick out twelve new compounds from ZINC database. Six hits revealed in the ligand database suggested potential ability to inhibit PiCYP51A. Compared to patent fungicide triazolone, the top three lead compounds had similar or higher affinity with the target enzyme, and accordingly, exhibited comparable or lower EC50 values to P. italicum isolates. The results could provide references for de novo antifungal drug design. Full article
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Open AccessArticle Lindane Bioremediation Capability of Bacteria Associated with the Demosponge Hymeniacidon perlevis
Mar. Drugs 2017, 15(4), 108; doi:10.3390/md15040108
Received: 23 January 2017 / Revised: 16 March 2017 / Accepted: 27 March 2017 / Published: 6 April 2017
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Abstract
Lindane is an organochlorine pesticide belonging to persistent organic pollutants (POPs) that has been widely used to treat agricultural pests. It is of particular concern because of its toxicity, persistence and tendency to bioaccumulate in terrestrial and aquatic ecosystems. In this context, we
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Lindane is an organochlorine pesticide belonging to persistent organic pollutants (POPs) that has been widely used to treat agricultural pests. It is of particular concern because of its toxicity, persistence and tendency to bioaccumulate in terrestrial and aquatic ecosystems. In this context, we assessed the role of bacteria associated with the sponge Hymeniacidon perlevis in lindane degradation. Seven bacteria isolates were characterized and identified. These isolates showed a remarkable capacity to utilize lindane as a sole carbon source leading to a percentage of residual lindane ranging from 3% to 13% after 12 days of incubation with the pesticide. The lindane metabolite, 1,3–6-pentachloro-cyclohexene, was identified as result of lindane degradation and determined by gas chromatography–mass spectrometry (GC–MS). The bacteria capable of lindane degradation were identified on the basis of the phenotypic characterization by morphological, biochemical and cultural tests, completed with 16S rDNA sequence analysis, and assigned to Mameliella phaeodactyli, Pseudovibrio ascidiaceicola, Oceanicaulis stylophorae, Ruegeria atlantica and to three new uncharacterized species. The results obtained are a prelude to the development of future strategies for the in situ bioremediation of lindane. Full article
(This article belongs to the Special Issue Biotransformations Utilizing Marine/Marine-Derived Bacteria and Fungi)
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Open AccessArticle An Unusual Diterpene—Enhygromic Acid and Deoxyenhygrolides from a Marine Myxobacterium, Enhygromyxa sp.
Mar. Drugs 2017, 15(4), 109; doi:10.3390/md15040109
Received: 1 March 2017 / Revised: 31 March 2017 / Accepted: 4 April 2017 / Published: 6 April 2017
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Abstract
Three new compounds, enhygromic acid (1) and deoxyenhygrolides A (2) and B (3), were isolated from a marine myxobacterium, Enhygromyxa sp. Compound 1 was found to be an acrylic acid derivative with a rare polycyclic carbon skeleton,
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Three new compounds, enhygromic acid (1) and deoxyenhygrolides A (2) and B (3), were isolated from a marine myxobacterium, Enhygromyxa sp. Compound 1 was found to be an acrylic acid derivative with a rare polycyclic carbon skeleton, decahydroacenaphthylene, by spectroscopic analyses. Compounds 2 and 3 were deoxy analogs of the known γ-alkylidenebutenolides, enhygrolides. Compound 1 exhibited cytotoxicity against B16 melanoma cells and anti-bacterial activity against Bacillus subtilis, and enhanced the NGF-induced neurite outgrowth of PC12 cells. Full article
(This article belongs to the Special Issue Marine Bioactive Natural Product Studies in Asia)
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Open AccessArticle Sulfated Hetero-Polysaccharides Protect SH-SY5Y Cells from H2O2-Induced Apoptosis by Affecting the PI3K/Akt Signaling Pathway
Mar. Drugs 2017, 15(4), 110; doi:10.3390/md15040110
Received: 14 February 2017 / Revised: 23 March 2017 / Accepted: 4 April 2017 / Published: 6 April 2017
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Abstract
Parkinson’s disease (PD) is one of the most common neurodegenerative diseases. Recent studies suggest that sulfated hetero-polysaccharides (UF) protect against developing PD. However, the detailed mechanisms of how UF suppress neuronal death have not been fully elucidated. We investigated the cytoprotective mechanisms of
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Parkinson’s disease (PD) is one of the most common neurodegenerative diseases. Recent studies suggest that sulfated hetero-polysaccharides (UF) protect against developing PD. However, the detailed mechanisms of how UF suppress neuronal death have not been fully elucidated. We investigated the cytoprotective mechanisms of UF using human dopaminergic neuroblastoma SH-SY5Y cells as a PD model. UF prevented H2O2-induced apoptotic cell death in SH-SY5Y cells in a dose-dependent manner. An examination of the PI3K/Akt upstream pathway revealed that UF-pretreated cells showed a decreased relative density of Akt, PI3K, and TrkA, and increased the phosphorylation of Akt, PI3K, and NGF; the PI3K inhibitor, LY294002, partially prevented this effect. An examination of the PI3K/Akt downstream pathway revealed the increased expression of the apoptosis-associated markers Bax, p53, CytC, and GSK3β, and the decreased expression of Bcl-2 in UF-treated cells. UF-treated cells also exhibited decreased caspase-3, caspase-8, and caspase-9 activities, which induced cell apoptosis. Our results demonstrate that UF affect the PI3K/Akt pathway, as well as downstream signaling. Therefore, the UF-mediated activation of PI3K/Akt could provide a new potential therapeutic strategy for neurodegenerative diseases associated with oxidative injury. These findings contribute to a better understanding of the critical roles of UF in the treatment of PD. Full article
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Open AccessArticle Bioactive Metabolites from the Deep Subseafloor Fungus Oidiodendron griseum UBOCC-A-114129
Mar. Drugs 2017, 15(4), 111; doi:10.3390/md15040111
Received: 14 December 2016 / Revised: 24 March 2017 / Accepted: 28 March 2017 / Published: 7 April 2017
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Abstract
Four bioactive compounds have been isolated from the fungus Oidiodendron griseum UBOCC-A-114129 cultivated from deep subsurface sediment. They were structurally characterized using a combination of LC–MS/MS and NMR analyses as fuscin and its derivatives (dihydrofuscin, dihydrosecofuscin, and secofuscin) and identified as polyketides. Albeit
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Four bioactive compounds have been isolated from the fungus Oidiodendron griseum UBOCC-A-114129 cultivated from deep subsurface sediment. They were structurally characterized using a combination of LC–MS/MS and NMR analyses as fuscin and its derivatives (dihydrofuscin, dihydrosecofuscin, and secofuscin) and identified as polyketides. Albeit those compounds were already obtained from terrestrial fungi, this is the first report of their production by an Oidiodendron species and by the deepest subseafloor isolate ever studied for biological activities. We report a weak antibacterial activity of dihydrosecofuscin and secofuscin mainly directed against Gram-positive bacteria (Minimum Inhibitory Concentration (MIC) equal to Minimum Bactericidal Concentration (MBC), in the range of 100 μg/mL). The activity on various protein kinases was also analyzed and revealed a significant inhibition of CDC2-like kinase-1 (CLK1) by dihysecofuscin. Full article
(This article belongs to the Special Issue Marine Fungal Natural Products)
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Open AccessArticle Promoting Wound Healing Using Low Molecular Weight Fucoidan in a Full-Thickness Dermal Excision Rat Model
Mar. Drugs 2017, 15(4), 112; doi:10.3390/md15040112
Received: 13 March 2017 / Revised: 1 April 2017 / Accepted: 5 April 2017 / Published: 7 April 2017
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Abstract
Low molecular weight fucoidan (LMF) has been reported to possess anti-inflammatory and antioxidant activities. Thus, we examined the effects of LMF extracted from Undaria pinnatifida on dermal wounds. Five round dermal wounds were created on the dorsal back of rats, and they were
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Low molecular weight fucoidan (LMF) has been reported to possess anti-inflammatory and antioxidant activities. Thus, we examined the effects of LMF extracted from Undaria pinnatifida on dermal wounds. Five round dermal wounds were created on the dorsal back of rats, and they were then treated topically with distilled water (DW), Madecasol Care™ (MC) or LMF at 200, 100 and 50 mg/mL, twice a day for a week. There were dose-dependent increases in wound contraction in the groups receiving LMF but not in the MC group, compared with the DW. Histopathological examination revealed that LMF treatment accelerated wound healing, which was supported by increases in granular tissue formation on day four post-treatment but a decrease on day seven, accompanied by an evident reduction in inflammatory cells. In the LMF-treated wounds, collagen distribution and angiogenesis were increased in the granular tissue on days four and seven post-treatment. Immunoreactive cells for transforming growth factor-β1, vascular endothelial growth factor receptor-2 or matrix metalloproteinases 9 were also increased, probably due to tissue remodeling. Furthermore, LMF treatment reduced lipid peroxidation and increased antioxidant activities. These suggested that LMF promotes dermal wound healing via complex and coordinated antioxidant, anti-inflammatory and growth factor-dependent activities. Full article
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Open AccessArticle Effects of Low-Molecular-Weight Fucoidan and High Stability Fucoxanthin on Glucose Homeostasis, Lipid Metabolism, and Liver Function in a Mouse Model of Type II Diabetes
Mar. Drugs 2017, 15(4), 113; doi:10.3390/md15040113
Received: 21 February 2017 / Revised: 27 March 2017 / Accepted: 4 April 2017 / Published: 7 April 2017
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Abstract
The combined effects of low-molecular-weight fucoidan (LMF) and fucoxanthin (Fx) in terms of antihyperglycemic, antihyperlipidemic, and hepatoprotective activities were investigated in a mouse model of type II diabetes. The intake of LMF, Fx, and LMF + Fx lowered the blood sugar and fasting
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The combined effects of low-molecular-weight fucoidan (LMF) and fucoxanthin (Fx) in terms of antihyperglycemic, antihyperlipidemic, and hepatoprotective activities were investigated in a mouse model of type II diabetes. The intake of LMF, Fx, and LMF + Fx lowered the blood sugar and fasting blood sugar levels, and increased serum adiponectin levels. The significant decrease in urinary sugar was only observed in LMF + Fx supplementation. LMF and Fx had ameliorating effects on the hepatic tissue of db/db mice by increasing hepatic glycogen and antioxidative enzymes, and LMF was more effective than Fx at improving hepatic glucose metabolism. As for glucose and lipid metabolism in the adipose tissue, the expression of insulin receptor substrate (IRS)-1, glucose transporter (GLUT), peroxisome proliferator-activated receptor gamma (PPARγ), and uncoupling protein (UCP)-1 mRNAs in the adipose tissue of diabetic mice was significantly upregulated by Fx and LMF + Fx, and levels of inflammatory adipocytokines, such as adiponectin, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6), were significantly modulated only by LMF + Fx supplementation. The efficacy of LMF + Fx supplementation on the decrease in urinary sugar and on glucose and lipid metabolism in the white adipose tissue of db/db mice was better than that of Fx or LMF alone, indicating the occurrence of a synergistic effect of LMF and Fx. Full article
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Open AccessArticle Prospecting Biotechnologically-Relevant Monooxygenases from Cold Sediment Metagenomes: An In Silico Approach
Mar. Drugs 2017, 15(4), 114; doi:10.3390/md15040114
Received: 31 January 2017 / Revised: 20 March 2017 / Accepted: 23 March 2017 / Published: 9 April 2017
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Abstract
The goal of this work was to identify sequences encoding monooxygenase biocatalysts with novel features by in silico mining an assembled metagenomic dataset of polar and subpolar marine sediments. The targeted enzyme sequences were Baeyer–Villiger and bacterial cytochrome P450 monooxygenases (CYP153). These enzymes
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The goal of this work was to identify sequences encoding monooxygenase biocatalysts with novel features by in silico mining an assembled metagenomic dataset of polar and subpolar marine sediments. The targeted enzyme sequences were Baeyer–Villiger and bacterial cytochrome P450 monooxygenases (CYP153). These enzymes have wide-ranging applications, from the synthesis of steroids, antibiotics, mycotoxins and pheromones to the synthesis of monomers for polymerization and anticancer precursors, due to their extraordinary enantio-, regio-, and chemo- selectivity that are valuable features for organic synthesis. Phylogenetic analyses were used to select the most divergent sequences affiliated to these enzyme families among the 264 putative monooxygenases recovered from the ~14 million protein-coding sequences in the assembled metagenome dataset. Three-dimensional structure modeling and docking analysis suggested features useful in biotechnological applications in five metagenomic sequences, such as wide substrate range, novel substrate specificity or regioselectivity. Further analysis revealed structural features associated with psychrophilic enzymes, such as broader substrate accessibility, larger catalytic pockets or low domain interactions, suggesting that they could be applied in biooxidations at room or low temperatures, saving costs inherent to energy consumption. This work allowed the identification of putative enzyme candidates with promising features from metagenomes, providing a suitable starting point for further developments. Full article
(This article belongs to the Special Issue Biotransformations Utilizing Marine/Marine-Derived Bacteria and Fungi)
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Open AccessArticle In Vitro Antioxidant Activities of Enzymatic Hydrolysate from Schizochytrium sp. and Its Hepatoprotective Effects on Acute Alcohol-Induced Liver Injury In Vivo
Mar. Drugs 2017, 15(4), 115; doi:10.3390/md15040115
Received: 1 October 2016 / Revised: 6 April 2017 / Accepted: 7 April 2017 / Published: 10 April 2017
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Abstract
Schizochytrium protein hydrolysate (SPH) was prepared through stepwise enzymatic hydrolysis by alcalase and flavourzyme sequentially. The proportion of hydrophobic amino acids of SPH was 34.71%. The molecular weight (MW) of SPH was principally concentrated at 180–3000 Da (52.29%). SPH was divided into two
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Schizochytrium protein hydrolysate (SPH) was prepared through stepwise enzymatic hydrolysis by alcalase and flavourzyme sequentially. The proportion of hydrophobic amino acids of SPH was 34.71%. The molecular weight (MW) of SPH was principally concentrated at 180–3000 Da (52.29%). SPH was divided into two fractions by ultrafiltration: SPH-I (MW < 3 kDa) and SPH-II (MW > 3 kDa). Besides showing lipid peroxidation inhibitory activity in vitro, SPH-I exhibited high DPPH and ABTS radicals scavenging activities with IC50 of 350 μg/mL and 17.5 μg/mL, respectively. In addition, the antioxidant activity of SPH-I was estimated in vivo using the model of acute alcohol-induced liver injury in mice. For the hepatoprotective effects, oral administration of SPH-I at different concentrations (100, 300 mg/kg BW) to the mice subjected to alcohol significantly decreased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and hepatic malondialdehyde (MDA) level compared to the untreated mice. Besides, SPH-I could effectively restore the hepatic superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities and glutathione (GSH) level. Results suggested that SPH was rich in biopeptides that could be exploited as antioxidant molecules against oxidative stress in human body. Full article
(This article belongs to the Special Issue Marine Proteins and Peptides)
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Open AccessCommunication Cloning and Functional Characterization of a Lycopene β-Cyclase from Macrophytic Red Alga Bangia fuscopurpurea
Mar. Drugs 2017, 15(4), 116; doi:10.3390/md15040116
Received: 10 November 2016 / Revised: 16 March 2017 / Accepted: 29 March 2017 / Published: 11 April 2017
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Abstract
Lycopene cyclases cyclize the open ends of acyclic lycopene (ψ,ψ-carotene) into β- or ε-ionone rings in the crucial bifurcation step of carotenoid biosynthesis. Among all carotenoid constituents, β-carotene (β,β-carotene) is found in all photosynthetic organisms, except for purple bacteria and heliobacteria, suggesting a
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Lycopene cyclases cyclize the open ends of acyclic lycopene (ψ,ψ-carotene) into β- or ε-ionone rings in the crucial bifurcation step of carotenoid biosynthesis. Among all carotenoid constituents, β-carotene (β,β-carotene) is found in all photosynthetic organisms, except for purple bacteria and heliobacteria, suggesting a ubiquitous distribution of lycopene β-cyclase activity in these organisms. In this work, we isolated a gene (BfLCYB) encoding a lycopene β-cyclase from Bangia fuscopurpurea, a red alga that is considered to be one of the primitive multicellular eukaryotic photosynthetic organisms and accumulates carotenoid constituents with both β- and ε-rings, including β-carotene, zeaxanthin, α-carotene (β,ε-carotene) and lutein. Functional complementation in Escherichia coli demonstrated that BfLCYB is able to catalyze cyclization of lycopene into monocyclic γ-carotene (β,ψ-carotene) and bicyclic β-carotene, and cyclization of the open end of monocyclic δ-carotene (ε,ψ-carotene) to produce α-carotene. No ε-cyclization activity was identified for BfLCYB. Sequence comparison showed that BfLCYB shares conserved domains with other functionally characterized lycopene cyclases from different organisms and belongs to a group of ancient lycopene cyclases. Although B. fuscopurpurea also synthesizes α-carotene and lutein, its enzyme-catalyzing ε-cyclization is still unknown. Full article
(This article belongs to the collection Marine Carotenoids)
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Open AccessFeature PaperArticle Four Aromatic Sulfates with an Inhibitory Effect against HCV NS3 Helicase from the Crinoid Alloeocomatella polycladia
Mar. Drugs 2017, 15(4), 117; doi:10.3390/md15040117
Received: 6 March 2017 / Revised: 4 April 2017 / Accepted: 6 April 2017 / Published: 11 April 2017
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Abstract
Bioassay-guided separation of a lipophilic extract of the crinoid Alloeocomatella polycladia, inhibiting the activity of HCV NS3 helicase, yielded two groups of molecules: cholesterol sulfate and four new aromatic sulfates 14. The structures of the aromatics were elucidated by
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Bioassay-guided separation of a lipophilic extract of the crinoid Alloeocomatella polycladia, inhibiting the activity of HCV NS3 helicase, yielded two groups of molecules: cholesterol sulfate and four new aromatic sulfates 14. The structures of the aromatics were elucidated by spectroscopic analysis in addition to theoretical studies. The aromatic sulfates 14 showed moderate inhibition against NS3 helicase with IC50 values of 71, 95, 7, and 5 μM, respectively. Full article
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Open AccessArticle Indole Derivatives Isolated from Brown Alga Sargassum thunbergii Inhibit Adipogenesis through AMPK Activation in 3T3-L1 Preadipocytes
Mar. Drugs 2017, 15(4), 119; doi:10.3390/md15040119
Received: 9 March 2017 / Revised: 31 March 2017 / Accepted: 7 April 2017 / Published: 12 April 2017
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Abstract
Seaweed, a popular and abundant food ingredient mainly consumed in Asian countries, is a good source of bioactive compounds with anti-obesity effects. However, the anti-obesity effects of Sargassum thunbergii have not yet been established. In this study, we isolated six indole derivatives (STCs)—indole-2-carboxaldehyde
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Seaweed, a popular and abundant food ingredient mainly consumed in Asian countries, is a good source of bioactive compounds with anti-obesity effects. However, the anti-obesity effects of Sargassum thunbergii have not yet been established. In this study, we isolated six indole derivatives (STCs)—indole-2-carboxaldehyde (STC-1), indole-3-carboxaldehyde (STC-2), indole-4-carboxaldehyde (STC-3), indole-5-carboxaldehyde (STC-4), indole-6-carboxaldehyde (STC-5), and indole-7-carboxaldehyde (STC-6)—from S. thunbergii and evaluated their inhibitory effects on adipocyte differentiation in 3T3-L1 cells. We found that STC-1 and STC-5 resulted in non-toxic inhibition of the differentiation of 3T3-L1 adipocytes and thus selected these compounds for further study. STC-1 and STC-5 significantly inhibited lipid accumulation and downregulated the expression of peroxisome proliferator-activated receptor-γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), and sterol regulatory element-binding protein 1c (SREBP-1c) in a dose-dependent manner. The specific mechanism mediating the effects of STC-1 and STC-5 was shown to be AMP-activated protein kinase (AMPK) activation. Our results demonstrated the inhibitory effect of STC-1 and STC-5 on adipogenesis through the activation of the AMPK signal pathway. Together, these findings suggested that STC-1 and STC-5 may be effective candidates for the prevention of obesity or obesity-related diseases. Full article
(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology II 2016)
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Open AccessArticle New Cytotoxic Secondary Metabolites from Marine Bryozoan Cryptosula pallasiana
Mar. Drugs 2017, 15(4), 120; doi:10.3390/md15040120
Received: 24 January 2017 / Revised: 10 April 2017 / Accepted: 11 April 2017 / Published: 13 April 2017
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Abstract
A new sterol, (23R)-methoxycholest-5,24-dien-3β-ol (1), two new ceramides, (2S,3R,4E,8E)-2-(tetradecanoylamino)-4,8-octadecadien-l,3-diol (6) and (2S,3R,2′R,4E,8E)-2-(tetradecanoylamino)-4,8-octadecadien-l,3,2′-triol (7), together with three known
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A new sterol, (23R)-methoxycholest-5,24-dien-3β-ol (1), two new ceramides, (2S,3R,4E,8E)-2-(tetradecanoylamino)-4,8-octadecadien-l,3-diol (6) and (2S,3R,2′R,4E,8E)-2-(tetradecanoylamino)-4,8-octadecadien-l,3,2′-triol (7), together with three known sterols (24), a lactone (5) and two ceramides (8,9), were isolated from the marine bryozoan Cryptosula pallasiana, collected at Huang Island of China. The structures of the new compounds were elucidated by extensive spectroscopic analyses, chemical methods and quantum electronic circular dichroism (ECD) calculations. Among the isolated compounds, sterol 1 possessed a rare side chain with a methoxy group at C-23, and a double bond between C-24 and C-25. Ceramides 6 and 7 possessed 14 carbons in their long-chain fatty acid base (FAB), which were different from the normal ceramides with 16 carbons in the FAB. Moreover, compounds 5 and 8 were isolated for the first time from marine bryozoans. Compounds 19 were evaluated for their cytotoxicity against human tumor cell lines HL-60, Hep-G2 and SGC-7901. The results showed that lactone 5 appears to have strong cytotoxicity against the test tumor cell lines, with IC50 values from 4.12 μM to 7.32 μM, and sterol 1 displayed moderate cytotoxicity with IC50 values between 12.34 μM and 18.37 μM, while ceramides 69 showed weak cytotoxicity with IC50 ranging from 21.13 μM to 58.15 μM. Full article
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Open AccessFeature PaperArticle Laucysteinamide A, a Hybrid PKS/NRPS Metabolite from a Saipan Cyanobacterium, cf. Caldora penicillata
Mar. Drugs 2017, 15(4), 121; doi:10.3390/md15040121
Received: 25 February 2017 / Revised: 2 April 2017 / Accepted: 6 April 2017 / Published: 14 April 2017
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Abstract
A bioactivity guided study of a cf. Caldora penicillata species, collected during a 2013 expedition to the Pacific island of Saipan, Northern Mariana Islands (a commonwealth of the USA), led to the isolation of a new thiazoline-containing alkaloid, laucysteinamide A (1).
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A bioactivity guided study of a cf. Caldora penicillata species, collected during a 2013 expedition to the Pacific island of Saipan, Northern Mariana Islands (a commonwealth of the USA), led to the isolation of a new thiazoline-containing alkaloid, laucysteinamide A (1). Laucysteinamide A is a new monomeric analogue of the marine cyanobacterial metabolite, somocystinamide A (2), a disulfide-bonded dimeric compound that was isolated previously from a Fijian marine cyanobacterium. The structure and absolute configuration of laucysteinamide A (1) was determined by a detailed analysis of its NMR, MS, and CD spectra. In addition, the highly bioactive lipid, curacin D (3), was also found to be present in this cyanobacterial extract. The latter compound was responsible for the potent cytotoxicity of this extract to H-460 human non-small cell lung cancer cells in vitro. Full article
(This article belongs to the Special Issue Marine Drugs as Antitumour Agents 2017)
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Open AccessArticle Efficacy of Low-Molecular-Weight Fucoidan as a Supplemental Therapy in Metastatic Colorectal Cancer Patients: A Double-Blind Randomized Controlled Trial
Mar. Drugs 2017, 15(4), 122; doi:10.3390/md15040122
Received: 24 March 2017 / Revised: 12 April 2017 / Accepted: 18 April 2017 / Published: 21 April 2017
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Abstract
Background: Low-molecular-weight fucoidan (LMF) is widely used as a food supplement for cancer patients. However, all of the studies are in vitro or were conducted using mice. Therefore, powerful clinical evidence for LMF use is relatively weak. This study aimed to evaluate the
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Background: Low-molecular-weight fucoidan (LMF) is widely used as a food supplement for cancer patients. However, all of the studies are in vitro or were conducted using mice. Therefore, powerful clinical evidence for LMF use is relatively weak. This study aimed to evaluate the efficacy of LMF as a supplemental therapy to chemo-target agents in metastatic colorectal cancer (mCRC) patients. Methods: We conducted a prospective, randomized, double-blind, controlled trial to evaluate the efficacy of LMF as a supplemental therapy to chemotarget agents in patients with metastatic colorectal cancer (mCRC). Sixty eligible patients with mCRC were included. Finally, 54 patients were enrolled, of whom 28 were included in the study group and 26 in the control group. The primary endpoint was the disease control rate (DCR), and secondary endpoints included the overall response rate (ORR), progression-free survival (PFS), overall survival (OS), adverse effects (AEs), and quality of life (QOL). Results: The DCRs were 92.8% and 69.2% in the study and control groups, respectively (p = 0.026), in a median follow-up period of 11.5 months. The OS, PFS, ORR, AEs, and QOL did not significantly differ between the two groups. Conclusion: This is the first clinical trial evaluating the efficacy of LMF as a supplemental therapy in the management of patients with mCRC. The results indicate that LMF combined with chemotarget agents significantly improved the DCR. Full article
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Open AccessArticle Identification of Tight-Binding Plasmepsin II and Falcipain 2 Inhibitors in Aqueous Extracts of Marine Invertebrates by the Combination of Enzymatic and Interaction-Based Assays
Mar. Drugs 2017, 15(4), 123; doi:10.3390/md15040123
Received: 28 February 2017 / Revised: 16 April 2017 / Accepted: 18 April 2017 / Published: 21 April 2017
PDF Full-text (5474 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Natural products from marine origin constitute a very promising and underexplored source of interesting compounds for modern biotechnological and pharmaceutical industries. However, their evaluation is quite challenging and requires specifically designed assays to reliably identify the compounds of interest in a highly heterogeneous
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Natural products from marine origin constitute a very promising and underexplored source of interesting compounds for modern biotechnological and pharmaceutical industries. However, their evaluation is quite challenging and requires specifically designed assays to reliably identify the compounds of interest in a highly heterogeneous and interfering context. In the present study, we describe a general strategy for the confident identification of tight-binding protease inhibitors in the aqueous extracts of 62 Cuban marine invertebrates, using Plasmodium falciparum hemoglobinases Plasmepsin II and Falcipain 2 as model enzymes. To this end, we first developed a screening strategy that combined enzymatic with interaction-based assays and then validated screening conditions using five reference extracts. Interferences were evaluated and minimized. The results from the massive screening of such extracts, the validation of several hits by a variety of interaction-based assays and the purification and functional characterization of PhPI, a multifunctional and reversible tight-binding inhibitor for Plasmepsin II and Falcipain 2 from the gorgonian Plexaura homomalla, are presented. Full article
(This article belongs to the Special Issue Enzyme Inhibitors of Marine Origin)
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Open AccessArticle Peptides, Peptidomimetics, and Polypeptides from Marine Sources: A Wealth of Natural Sources for Pharmaceutical Applications
Mar. Drugs 2017, 15(4), 124; doi:10.3390/md15040124
Received: 21 December 2016 / Revised: 11 April 2017 / Accepted: 18 April 2017 / Published: 22 April 2017
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Abstract
Nature provides a variety of peptides that are expressed in most living species. Evolutionary pressure and natural selection have created and optimized these peptides to bind to receptors with high affinity. Hence, natural resources provide an abundant chemical space to be explored in
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Nature provides a variety of peptides that are expressed in most living species. Evolutionary pressure and natural selection have created and optimized these peptides to bind to receptors with high affinity. Hence, natural resources provide an abundant chemical space to be explored in peptide-based drug discovery. Marine peptides can be extracted by simple solvent extraction techniques. The advancement of analytical techniques has made it possible to obtain pure peptides from natural resources. Extracted peptides have been evaluated as possible therapeutic agents for a wide range of diseases, including antibacterial, antifungal, antidiabetic and anticancer activity as well as cardiovascular and neurotoxin activity. Although marine resources provide thousands of possible peptides, only a few peptides derived from marine sources have reached the pharmaceutical market. This review focuses on some of the peptides derived from marine sources in the past ten years and gives a brief review of those that are currently in clinical trials or on the market. Full article
(This article belongs to the Special Issue Drug Design Based on Marine Natural Product Scaffolds)
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Open AccessReview Marine Peptides as Potential Agents for the Management of Type 2 Diabetes Mellitus—A Prospect
Mar. Drugs 2017, 15(4), 88; doi:10.3390/md15040088
Received: 30 January 2017 / Revised: 17 March 2017 / Accepted: 20 March 2017 / Published: 23 March 2017
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Abstract
An increasing prevalence of diabetes is known as a main risk for human health in the last future worldwide. There is limited evidence on the potential management of type 2 diabetes mellitus using bioactive peptides from marine organisms, besides from milk and beans.
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An increasing prevalence of diabetes is known as a main risk for human health in the last future worldwide. There is limited evidence on the potential management of type 2 diabetes mellitus using bioactive peptides from marine organisms, besides from milk and beans. We summarized here recent advances in our understanding of the regulation of glucose metabolism using bioactive peptides from natural proteins, including regulation of insulin-regulated glucose metabolism, such as protection and reparation of pancreatic β-cells, enhancing glucose-stimulated insulin secretion and influencing the sensitivity of insulin and the signaling pathways, and inhibition of bioactive peptides to dipeptidyl peptidase IV, α-amylase and α-glucosidase activities. The present paper tried to understand the underlying mechanism involved and the structure characteristics of bioactive peptides responsible for its antidiabetic activities to prospect the utilization of rich marine organism proteins. Full article
(This article belongs to the Special Issue Marine Proteins and Peptides)
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Open AccessReview An Overview of the Protective Effects of Chitosan and Acetylated Chitosan Oligosaccharides against Neuronal Disorders
Mar. Drugs 2017, 15(4), 89; doi:10.3390/md15040089
Received: 14 November 2016 / Revised: 7 March 2017 / Accepted: 15 March 2017 / Published: 23 March 2017
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Abstract
Chitin is the second most abundant biopolymer on Earth and is mainly comprised of a marine invertebrate, consisting of repeating β-1,4 linked N-acetylated glucosamine units, whereas its N-deacetylated product, chitosan, has broad medical applications. Interestingly, chitosan oligosaccharides have therapeutic effects on different types
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Chitin is the second most abundant biopolymer on Earth and is mainly comprised of a marine invertebrate, consisting of repeating β-1,4 linked N-acetylated glucosamine units, whereas its N-deacetylated product, chitosan, has broad medical applications. Interestingly, chitosan oligosaccharides have therapeutic effects on different types of neuronal disorders, including, but not limited to, Alzheimer’s disease, Parkinson’s disease, and nerve crush injury. A common link among neuronal disorders is observed at a sub-cellular level, such as atypical protein assemblies and induced neuronal death. Chronic activation of innate immune responses that lead to neuronal injury is also common in these diseases. Thus, the common mechanisms of neuronal disorders might explain the general therapeutic effects of chitosan oligosaccharides and their derivatives in these diseases. This review provides an update on the pathogenesis and therapy for neuronal disorders and will be mainly focused on the recent progress made towards the neuroprotective properties of chitosan and acetylated chitosan oligosaccharides. Their structural features and the underlying molecular mechanisms will also be discussed. Full article
(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan II, 2017)
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Open AccessFeature PaperReview Enzymatic Processes in Marine Biotechnology
Mar. Drugs 2017, 15(4), 93; doi:10.3390/md15040093
Received: 17 February 2017 / Revised: 16 March 2017 / Accepted: 20 March 2017 / Published: 25 March 2017
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Abstract
In previous review articles the attention of the biocatalytically oriented scientific community towards the marine environment as a source of biocatalysts focused on the habitat-related properties of marine enzymes. Updates have already appeared in the literature, including marine examples of oxidoreductases, hydrolases, transferases,
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In previous review articles the attention of the biocatalytically oriented scientific community towards the marine environment as a source of biocatalysts focused on the habitat-related properties of marine enzymes. Updates have already appeared in the literature, including marine examples of oxidoreductases, hydrolases, transferases, isomerases, ligases, and lyases ready for food and pharmaceutical applications. Here a new approach for searching the literature and presenting a more refined analysis is adopted with respect to previous surveys, centering the attention on the enzymatic process rather than on a single novel activity. Fields of applications are easily individuated: (i) the biorefinery value-chain, where the provision of biomass is one of the most important aspects, with aquaculture as the prominent sector; (ii) the food industry, where the interest in the marine domain is similarly developed to deal with the enzymatic procedures adopted in food manipulation; (iii) the selective and easy extraction/modification of structurally complex marine molecules, where enzymatic treatments are a recognized tool to improve efficiency and selectivity; and (iv) marine biomarkers and derived applications (bioremediation) in pollution monitoring are also included in that these studies could be of high significance for the appreciation of marine bioprocesses. Full article
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Open AccessReview Multifaceted Applications of Chitosan in Cancer Drug Delivery and Therapy
Mar. Drugs 2017, 15(4), 96; doi:10.3390/md15040096
Received: 27 January 2017 / Revised: 17 March 2017 / Accepted: 20 March 2017 / Published: 27 March 2017
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Abstract
Chitosan is a versatile polysaccharide of biological origin. Due to the biocompatible and biodegradable nature of chitosan, it is intensively utilized in biomedical applications in scaffold engineering as an absorption enhancer, and for bioactive and controlled drug release. In cancer therapy, chitosan has
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Chitosan is a versatile polysaccharide of biological origin. Due to the biocompatible and biodegradable nature of chitosan, it is intensively utilized in biomedical applications in scaffold engineering as an absorption enhancer, and for bioactive and controlled drug release. In cancer therapy, chitosan has multifaceted applications, such as assisting in gene delivery and chemotherapeutic delivery, and as an immunoadjuvant for vaccines. The present review highlights the recent applications of chitosan and chitosan derivatives in cancer therapy. Full article
(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan II, 2017)
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Open AccessFeature PaperReview Current Status of Marine-Derived Compounds as Warheads in Anti-Tumor Drug Candidates
Mar. Drugs 2017, 15(4), 99; doi:10.3390/md15040099
Received: 28 February 2017 / Revised: 24 March 2017 / Accepted: 27 March 2017 / Published: 29 March 2017
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Abstract
In this review, we have attempted to describe all of the antibody–drug conjugates using a marine-derived compound as the “warhead”, that are currently in clinical trials as listed in the current version of the NIH clinical trials database (clinicaltrials.gov). In searching this database,
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In this review, we have attempted to describe all of the antibody–drug conjugates using a marine-derived compound as the “warhead”, that are currently in clinical trials as listed in the current version of the NIH clinical trials database (clinicaltrials.gov). In searching this database, we used the beta-test version currently available, as it permitted more specific search parameters, since the regular version did not always find trials that had been completed in the past with some agents. We also added small discussion sections on candidates that are still at the preclinical stage, including a derivative of diazonamide that has an unusual interaction with tubulin (DZ-23840), which may also be a potential warhead in the future. Full article
(This article belongs to the Special Issue Marine Drugs as Antitumour Agents 2017)
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Open AccessReview From Marine Venoms to Drugs: Efficiently Supported by a Combination of Transcriptomics and Proteomics
Mar. Drugs 2017, 15(4), 103; doi:10.3390/md15040103
Received: 1 February 2017 / Revised: 20 March 2017 / Accepted: 29 March 2017 / Published: 30 March 2017
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Abstract
The potential of marine natural products to become new drugs is vast; however, research is still in its infancy. The chemical and biological diversity of marine toxins is immeasurable and as such an extraordinary resource for the discovery of new drugs. With the
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The potential of marine natural products to become new drugs is vast; however, research is still in its infancy. The chemical and biological diversity of marine toxins is immeasurable and as such an extraordinary resource for the discovery of new drugs. With the rapid development of next-generation sequencing (NGS) and liquid chromatography–tandem mass spectrometry (LC-MS/MS), it has been much easier and faster to identify more toxins and predict their functions with bioinformatics pipelines, which pave the way for novel drug developments. Here we provide an overview of related bioinformatics pipelines that have been supported by a combination of transcriptomics and proteomics for identification and function prediction of novel marine toxins. Full article
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Open AccessReview Marine Microbial-Derived Molecules and Their Potential Use in Cosmeceutical and Cosmetic Products
Mar. Drugs 2017, 15(4), 118; doi:10.3390/md15040118
Received: 1 March 2017 / Revised: 30 March 2017 / Accepted: 5 April 2017 / Published: 12 April 2017
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Abstract
The oceans encompass a wide range of habitats and environmental conditions, which host a huge microbial biodiversity. The unique characteristics of several marine systems have driven a variety of biological adaptations, leading to the production of a large spectrum of bioactive molecules. Fungi,
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The oceans encompass a wide range of habitats and environmental conditions, which host a huge microbial biodiversity. The unique characteristics of several marine systems have driven a variety of biological adaptations, leading to the production of a large spectrum of bioactive molecules. Fungi, fungi-like protists (such as thraustochytrids) and bacteria are among the marine organisms with the highest potential of producing bioactive compounds, which can be exploited for several commercial purposes, including cosmetic and cosmeceutical ones. Mycosporines and mycosporine-like amino acids, carotenoids, exopolysaccharides, fatty acids, chitosan and other compounds from these microorganisms might represent a sustainable, low-cost and fast-production alternative to other natural molecules used in photo-protective, anti-aging and skin-whitening products for face, body and hair care. Here, we review the existing knowledge of these compounds produced by marine microorganisms, highlighting the marine habitats where such compounds are preferentially produced and their potential application in cosmetic and cosmeceutical fields. Full article
(This article belongs to the Special Issue Biotransformations Utilizing Marine/Marine-Derived Bacteria and Fungi)
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