Marine Drugs

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Open AccessArticle

Cembrene Diterpenoids with Ether Linkages from Sarcophyton ehrenbergi: An Anti-Proliferation and Molecular-Docking Assessment

by Mohamed-Elamir F. Hegazy, Abdelsamed I. Elshamy, Tarik A. Mohamed, Ahmed R. Hamed, Mahmoud A. A. Ibrahim, Shinji Ohta and Paul W. Paré

Mar. Drugs 2017, 15(6), 192; https://doi.org/10.3390/md15060192 - 21 Jun 2017

Cited by 41 | Viewed by 5764

Abstract

Three new cembrene diterpenoids, sarcoehrenbergilid A–C (1–3), along with four known diterpenoids, sarcophine (4), (+)-7α,8β-dihydroxydeepoxysarcophine (5), sinulolide A (6), and sinulolide B (7), and one steroid, sardisterol (8), were [...] Read more.

Three new cembrene diterpenoids, sarcoehrenbergilid A–C (1–3), along with four known diterpenoids, sarcophine (4), (+)-7α,8β-dihydroxydeepoxysarcophine (5), sinulolide A (6), and sinulolide B (7), and one steroid, sardisterol (8), were isolated and characterized from a solvent extract of the Red Sea soft coral Sarcophyton ehrenbergi. Chemical structures were elucidated by NMR and MS analyses with absolute stereochemistry determined by X-ray analysis. Since these isolated cembrene diterpenes contained 10 or more carbons in a large flexible ring, conformer stabilities were examined based on density functional theory calculations. Anti-proliferative activities for 1–8 were evaluated against three human tumor cell lines of different origins including the: lung (A549), colon (Caco-2), and liver (HepG2). Sardisterol (8) was the most potent of the metabolites isolated with an IC₅₀ of 27.3 µM against the A549 cell line. Since an elevated human-cancer occurrence is associated with an aberrant receptor function for the epidermal growth factor receptor (EGFR), molecular docking studies were used to examine preferential metabolite interactions/binding and probe the mode-of-action for metabolite-anti tumor activity. Full article

(This article belongs to the Collection Marine Compounds and Cancer)

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Open AccessArticle

Asperentin B, a New Inhibitor of the Protein Tyrosine Phosphatase 1B

by Jutta Wiese, Hülya Aldemir, Rolf Schmaljohann, Tobias A. M. Gulder and Johannes F. Imhoff

Mar. Drugs 2017, 15(6), 191; https://doi.org/10.3390/md15060191 - 21 Jun 2017

Cited by 32 | Viewed by 5016

Abstract

In the frame of studies on secondary metabolites produced by fungi from deep-sea environments we have investigated inhibitors of enzymes playing key roles in signaling cascades of biochemical pathways relevant for the treatment of diseases. Here we report on a new inhibitor of [...] Read more.

In the frame of studies on secondary metabolites produced by fungi from deep-sea environments we have investigated inhibitors of enzymes playing key roles in signaling cascades of biochemical pathways relevant for the treatment of diseases. Here we report on a new inhibitor of the human protein tyrosine phosphatase 1B (PTP1B), a target in the signaling pathway of insulin. A new asperentin analog is produced by an Aspergillus sydowii strain isolated from the sediment of the deep Mediterranean Sea. Asperentin B (1) contains an additional phenolic hydroxy function at C-6 and exhibits an IC₅₀ value against PTP1B of 2 μM in vitro, which is six times stronger than the positive control, suramin. Interestingly, asperentin (2) did not show any inhibition of this enzymatic activity. Asperentin B (1) is discussed as possible therapeutic agents for type 2 diabetes and sleeping sickness. Full article

(This article belongs to the Special Issue Marine Fungal Natural Products)

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Open AccessArticle

The Identification of a SIRT6 Activator from Brown Algae Fucus distichus

by Minna K. Rahnasto-Rilla, Padraig McLoughlin, Tomasz Kulikowicz, Maire Doyle, Vilhelm A. Bohr, Maija Lahtela-Kakkonen, Luigi Ferrucci, Maria Hayes and Ruin Moaddel

Mar. Drugs 2017, 15(6), 190; https://doi.org/10.3390/md15060190 - 21 Jun 2017

Cited by 38 | Viewed by 8401

Abstract

Brown seaweeds contain many bioactive compounds, including polyphenols, polysaccharides, fucosterol, and fucoxantin. These compounds have several biological activities, including anti-inflammatory, hepatoprotective, anti-tumor, anti-hypertensive, and anti-diabetic activity, although in most cases their mechanisms of action are not understood. In this study, extracts generated from [...] Read more.

Brown seaweeds contain many bioactive compounds, including polyphenols, polysaccharides, fucosterol, and fucoxantin. These compounds have several biological activities, including anti-inflammatory, hepatoprotective, anti-tumor, anti-hypertensive, and anti-diabetic activity, although in most cases their mechanisms of action are not understood. In this study, extracts generated from five brown algae (Fucus dichitus, Fucus vesiculosus (Linnaeus), Cytoseira tamariscofolia, Cytoseira nodacaulis, Alaria esculenta) were tested for their ability to activate SIRT6 resulting in H3K9 deacetylation. Three of the five macroalgal extracts caused a significant increase of H3K9 deacetylation, and the effect was most pronounced for F. dichitus. The compound responsible for this in vitro activity was identified by mass spectrometry as fucoidan. Full article

(This article belongs to the Collection Marine Polysaccharides)

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Open AccessArticle

Development of a Dunaliella tertiolecta Strain with Increased Zeaxanthin Content Using Random Mutagenesis

by Minjae Kim, Junhak Ahn, Hancheol Jeon and EonSeon Jin

Mar. Drugs 2017, 15(6), 189; https://doi.org/10.3390/md15060189 - 21 Jun 2017

Cited by 44 | Viewed by 5712

Abstract

Zeaxanthin is a xanthophyll pigment that is regarded as one of the best carotenoids for the prevention and treatment of degenerative diseases. In the worldwide natural products market, consumers prefer pigments that have been produced from biological sources. In this study, a Dunaliella [...] Read more.

Zeaxanthin is a xanthophyll pigment that is regarded as one of the best carotenoids for the prevention and treatment of degenerative diseases. In the worldwide natural products market, consumers prefer pigments that have been produced from biological sources. In this study, a Dunaliella tertiolecta strain that has 10–15% higher cellular zeaxanthin content than the parent strain (zea1), was obtained by random mutagenesis using ethyl methanesulfonate (EMS) as a mutagen. This mutant, mp3, was grown under various salinities and light intensities to optimize culture conditions for zeaxanthin production. The highest cellular zeaxanthin content was observed at 1.5 M NaCl and 65–85 μmol photons·m⁻²·s⁻¹, and the highest daily zeaxanthin productivity was observed at 0.6 M NaCl and 140–160 μmol photons·m⁻²·s⁻¹. The maximal yield of zeaxanthin from mp3 in fed-batch culture was 8 mg·L⁻¹, which was obtained at 0.6 M NaCl and 140–160 μmol photons·m⁻²·s⁻¹. These results suggest that random mutagenesis with EMS is useful for generating D. tertiolecta strains with increased zeaxanthin content, and also suggest optimal culture conditions for the enhancement of biomass and zeaxanthin production by the zeaxanthin accumulating mutant strains. Full article

(This article belongs to the Special Issue Marine Microalgae)

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Open AccessArticle

Effects of Tetrodotoxin in Mouse Models of Visceral Pain

by Rafael González-Cano, Miguel Ángel Tejada, Antonia Artacho-Cordón, Francisco Rafael Nieto, José Manuel Entrena, John N. Wood and Cruz Miguel Cendán

Mar. Drugs 2017, 15(6), 188; https://doi.org/10.3390/md15060188 - 21 Jun 2017

Cited by 28 | Viewed by 8602

Abstract

Visceral pain is very common and represents a major unmet clinical need for which current pharmacological treatments are often insufficient. Tetrodotoxin (TTX) is a potent neurotoxin that exerts analgesic actions in both humans and rodents under different somatic pain conditions, but its effect [...] Read more.

Visceral pain is very common and represents a major unmet clinical need for which current pharmacological treatments are often insufficient. Tetrodotoxin (TTX) is a potent neurotoxin that exerts analgesic actions in both humans and rodents under different somatic pain conditions, but its effect has been unexplored in visceral pain. Therefore, we tested the effects of systemic TTX in viscero-specific mouse models of chemical stimulation of the colon (intracolonic instillation of capsaicin and mustard oil) and intraperitoneal cyclophosphamide-induced cystitis. The subcutaneous administration of TTX dose-dependently inhibited the number of pain-related behaviors in all evaluated pain models and reversed the referred mechanical hyperalgesia (examined by stimulation of the abdomen with von Frey filaments) induced by capsaicin and cyclophosphamide, but not that induced by mustard oil. Morphine inhibited both pain responses and the referred mechanical hyperalgesia in all tests. Conditional nociceptor‑specific Na_v1.7 knockout mice treated with TTX showed the same responses as littermate controls after the administration of the algogens. No motor incoordination after the administration of TTX was observed. These results suggest that blockade of TTX-sensitive sodium channels, but not Na_v1.7 subtype alone, by systemic administration of TTX might be a potential therapeutic strategy for the treatment of visceral pain. Full article

(This article belongs to the Special Issue Tetrodotoxin)

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Open AccessArticle

The Sea Urchin Arbacia lixula: A Novel Natural Source of Astaxanthin

by Paola Cirino, Christophe Brunet, Martina Ciaravolo, Christian Galasso, Luigi Musco, Tomás Vega Fernández, Clementina Sansone and Alfonso Toscano

Mar. Drugs 2017, 15(6), 187; https://doi.org/10.3390/md15060187 - 21 Jun 2017

Cited by 18 | Viewed by 6319

Abstract

Several echinoderms, including sea urchins, are valuable sources of bioactive compounds but their nutraceutical potential is largely unexplored. In fact, the gonads of some sea urchin species contain antioxidants including carotenoids and polyhydroxylated naphthoquinones (PHNQ’s), such as echinochrome A. Astaxanthin is known to [...] Read more.

Several echinoderms, including sea urchins, are valuable sources of bioactive compounds but their nutraceutical potential is largely unexplored. In fact, the gonads of some sea urchin species contain antioxidants including carotenoids and polyhydroxylated naphthoquinones (PHNQ’s), such as echinochrome A. Astaxanthin is known to have particular bioactivity for the prevention of neurodegenerative diseases. This carotenoid is produced by microalgae, while several marine invertebrates can bioaccumulate or synthetize it from metabolic precursors. We determined the carotenoid content and analyzed the bioactivity potential of non-harvested Atlantic-Mediterranean sea urchin Arbacia lixula. The comparison of methanol crude extracts obtained from eggs of farmed and wild specimens revealed a higher bioactivity in farmed individuals fed with a customized fodder. HPLC-analysis revealed a high concentration of astaxanthin (27.0 μg/mg), which was the only pigment observed. This study highlights the potential of farmed A. lixula as a new source of the active stereoisomer of astaxanthin. Full article

(This article belongs to the Special Issue Marine Secondary Metabolite II, 2017)

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Open AccessArticle

Crude Fucoidan Extracts Impair Angiogenesis in Models Relevant for Bone Regeneration and Osteosarcoma via Reduction of VEGF and SDF-1

by Fanlu Wang, Harald Schmidt, Dijana Pavleska, Thees Wermann, Andreas Seekamp and Sabine Fuchs

Mar. Drugs 2017, 15(6), 186; https://doi.org/10.3390/md15060186 - 20 Jun 2017

Cited by 42 | Viewed by 5970

Abstract

The marine origin polysaccharide fucoidan combines multiple biological activities. As demonstrated by various studies in vitro and in vivo, fucoidans show anti-viral, anti-tumor, anti-oxidant, anti-inflammatory and anti-coagulant properties, although the detailed molecular action remains to be elucidated. The aim of the present study [...] Read more.

The marine origin polysaccharide fucoidan combines multiple biological activities. As demonstrated by various studies in vitro and in vivo, fucoidans show anti-viral, anti-tumor, anti-oxidant, anti-inflammatory and anti-coagulant properties, although the detailed molecular action remains to be elucidated. The aim of the present study is to assess the impact of crude fucoidan extracts, on the formation of vascular structures in co-culture models relevant for bone vascularization during bone repair and for vascularization processes in osteosarcoma. The co-cultures consisted of bone marrow derived mesenchymal stem cells, respectively the osteosarcoma cell line MG63, and human blood derived outgrowth endothelial cells (OEC). The concentration dependent effects on the metabolic activity on endothelial cells and osteoblast cells were first assessed using monocultures of OEC, MSC and MG63 suggesting a concentration of 100 µg/mL as a suitable concentration for further experiments. In co-cultures fucoidan significantly reduced angiogenesis in MSC/OEC but also in MG63/OEC co-cultures suggesting a potential application of fucoidan to lower the vascularization in bone tumors such as osteosarcoma. This was associated with a decrease in VEGF (vascular endothelial growth factor) and SDF-1 (stromal derived factor-1) on the protein level, both related to the control of angiogenesis and furthermore discussed as crucial factors in osteosarcoma progression and metastasis. In terms of bone formation, fucoidan slightly lowered on the calcification process in MSC monocultures and MSC/OEC co-cultures. In summary, these data suggest the suitability of lower fucoidan doses to limit angiogenesis for instance in osteosarcoma. Full article

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Open AccessArticle

The Novel Mechanisms Concerning the Inhibitions of Palmitate-Induced Proinflammatory Factor Releases and Endogenous Cellular Stress with Astaxanthin on MIN6 β-Cells

by Atsuko Kitahara, Kazuto Takahashi, Naru Morita, Toshitaka Murashima, Hirohisa Onuma, Yoshikazu Sumitani, Toshiaki Tanaka, Takuma Kondo, Toshio Hosaka and Hitoshi Ishida

Mar. Drugs 2017, 15(6), 185; https://doi.org/10.3390/md15060185 - 20 Jun 2017

Cited by 17 | Viewed by 4539

Abstract

Astaxanthin, an antioxidant agent, can protect pancreatic β-cells of db/db mice from glucotoxicity and resolve chronic inflammation in adipose tissue. Nonetheless, the effects of astaxanthin on free-fatty-acid-induced inflammation and cellular stress in β-cells remain to be demonstrated. Meanwhile, palmitate enhances the secretion of [...] Read more.

Astaxanthin, an antioxidant agent, can protect pancreatic β-cells of db/db mice from glucotoxicity and resolve chronic inflammation in adipose tissue. Nonetheless, the effects of astaxanthin on free-fatty-acid-induced inflammation and cellular stress in β-cells remain to be demonstrated. Meanwhile, palmitate enhances the secretion of pro-inflammatory adipokines monocyte chemoattractant protein-1 (MCP-1) and vascular endothelial growth factor (VEGF₁₂₀). We therefore investigated the influence of astaxanthin on palmitate-stimulated MCP-1 and VEGF₁₂₀ secretion in mouse insulinoma (MIN6) pancreatic β-cells. Furthermore, whether astaxanthin prevents cellular stress in MIN6 cells was also assessed. Pre-treatment with astaxanthin or with N-acetyl-cysteine (NAC) which is an antioxidant drug, significantly attenuated the palmitate-induced MCP-1 release through downregulation of phosphorylated c-Jun NH₂-terminal protein kinase (JNK) pathways, and suppressed VEGF₁₂₀ through the PI3K/Akt pathways relative to the cells stimulated with palmitate alone. In addition, palmitate significantly upregulated homologous protein (CHOP) and anti-glucose-regulated protein (GRP78), which are endoplasmic reticulum (ER) stress markers, in MIN6 cells. On the other hand, astaxanthin attenuated the increased CHOP content, but further up-regulated palmitate-stimulated GRP78 protein expression. By contrast, NAC had no effects on either CHOP or GRP78 enhancement induced by palmitate in MIN6 cells. In conclusion, astaxanthin diminishes the palmitate-stimulated increase in MCP-1 secretion via the downregulation of JNK pathways in MIN6 cells, and affects VEGF₁₂₀ secretion through PI3K/Akt pathways. Moreover, astaxanthin can prevent not only oxidative stress caused endogenously by palmitate but also ER stress, which NAC fails to attenuate, via upregulation of GRP78, an ER chaperon. Full article

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Open AccessArticle

Biotechnological Potential of Cold Adapted Pseudoalteromonas spp. Isolated from ‘Deep Sea’ Sponges

by Erik Borchert, Stephen Knobloch, Emilie Dwyer, Sinéad Flynn, Stephen A. Jackson, Ragnar Jóhannsson, Viggó T. Marteinsson, Fergal O’Gara and Alan D. W. Dobson

Mar. Drugs 2017, 15(6), 184; https://doi.org/10.3390/md15060184 - 19 Jun 2017

Cited by 19 | Viewed by 6573

Abstract

The marine genus Pseudoalteromonas is known for its versatile biotechnological potential with respect to the production of antimicrobials and enzymes of industrial interest. We have sequenced the genomes of three Pseudoalteromonas sp. strains isolated from different deep sea sponges on the Illumina MiSeq [...] Read more.

The marine genus Pseudoalteromonas is known for its versatile biotechnological potential with respect to the production of antimicrobials and enzymes of industrial interest. We have sequenced the genomes of three Pseudoalteromonas sp. strains isolated from different deep sea sponges on the Illumina MiSeq platform. The isolates have been screened for various industrially important enzymes and comparative genomics has been applied to investigate potential relationships between the isolates and their host organisms, while comparing them to free-living Pseudoalteromonas spp. from shallow and deep sea environments. The genomes of the sponge associated Pseudoalteromonas strains contained much lower levels of potential eukaryotic-like proteins which are known to be enriched in symbiotic sponge associated microorganisms, than might be expected for true sponge symbionts. While all the Pseudoalteromonas shared a large distinct subset of genes, nonetheless the number of unique and accessory genes is quite large and defines the pan-genome as open. Enzymatic screens indicate that a vast array of enzyme activities is expressed by the isolates, including β-galactosidase, β-glucosidase, and protease activities. A β-glucosidase gene from one of the Pseudoalteromonas isolates, strain EB27 was heterologously expressed in Escherichia coli and, following biochemical characterization, the recombinant enzyme was found to be cold-adapted, thermolabile, halotolerant, and alkaline active. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology II 2016)

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Open AccessArticle

Compositional Characteristics and In Vitro Evaluations of Antioxidant and Neuroprotective Properties of Crude Extracts of Fucoidan Prepared from Compressional Puffing-Pretreated Sargassum crassifolium

by Wen-Ning Yang, Po-Wei Chen and Chun-Yung Huang

Mar. Drugs 2017, 15(6), 183; https://doi.org/10.3390/md15060183 - 18 Jun 2017

Cited by 43 | Viewed by 5991

Abstract

Fucoidan, a fucose-containing sulfated polysaccharide with diverse biological functions, is mainly recovered from brown algae. In this study, we utilized a compressional-puffing process (CPP) to pretreat Sargassum crassifolium (SC) and extracted fucoidans from SC by warm water. Three fucoidan extracts (SC1: puffing at [...] Read more.

Fucoidan, a fucose-containing sulfated polysaccharide with diverse biological functions, is mainly recovered from brown algae. In this study, we utilized a compressional-puffing process (CPP) to pretreat Sargassum crassifolium (SC) and extracted fucoidans from SC by warm water. Three fucoidan extracts (SC1: puffing at 0 kg/cm²; SC2: puffing at 1.7 kg/cm²; and SC3: puffing at 6.3 kg/cm²) were obtained, and their composition, and antioxidant and neuroprotective activities were examined. The results suggest that CPP decreased the bulk density of algal samples, expanded the algal cellular structures, and eliminated the unpleasant algal odor. The extraction yields of fucoidans were increased and impurities of fucoidans were decreased by increasing the pressures used in CPP. The SC1–SC3 extracts displayed various characteristics of fucoidan as illustrated by the analyses of composition, Fourier transform infrared (FTIR) spectroscopy, and molecular weight. All three extracts SC1–SC3 showed antioxidant activity dose-dependently. Although both SC1 and SC2 possessed high and similar neuronal protective properties, SC2 showed a higher extraction yield, higher efficacy in the reversion of H₂O₂-induced cytotoxicity in rat pheochromocytoma PC-12 cells, and lower impurities compared with SC1, and thus SC2 is suggested as a good candidate for a therapeutic agent in the preventive treatment of neurodegenerative diseases. Full article

(This article belongs to the Special Issue Nutraceuticals and Functional Foods)

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Open AccessReview

Microbial Diseases of Bivalve Mollusks: Infections, Immunology and Antimicrobial Defense

by Carla Zannella, Francesco Mosca, Francesca Mariani, Gianluigi Franci, Veronica Folliero, Marilena Galdiero, Pietro Giorgio Tiscar and Massimiliano Galdiero

Mar. Drugs 2017, 15(6), 182; https://doi.org/10.3390/md15060182 - 17 Jun 2017

Cited by 138 | Viewed by 13808

Abstract

A variety of bivalve mollusks (phylum Mollusca, class Bivalvia) constitute a prominent commodity in fisheries and aquacultures, but are also crucial in order to preserve our ecosystem’s complexity and function. Bivalve mollusks, such as clams, mussels, oysters and scallops, are relevant bred species, [...] Read more.

A variety of bivalve mollusks (phylum Mollusca, class Bivalvia) constitute a prominent commodity in fisheries and aquacultures, but are also crucial in order to preserve our ecosystem’s complexity and function. Bivalve mollusks, such as clams, mussels, oysters and scallops, are relevant bred species, and their global farming maintains a high incremental annual growth rate, representing a considerable proportion of the overall fishery activities. Bivalve mollusks are filter feeders; therefore by filtering a great quantity of water, they may bioaccumulate in their tissues a high number of microorganisms that can be considered infectious for humans and higher vertebrates. Moreover, since some pathogens are also able to infect bivalve mollusks, they are a threat for the entire mollusk farming industry. In consideration of the leading role in aquaculture and the growing financial importance of bivalve farming, much interest has been recently devoted to investigate the pathogenesis of infectious diseases of these mollusks in order to be prepared for public health emergencies and to avoid dreadful income losses. Several bacterial and viral pathogens will be described herein. Despite the minor complexity of the organization of the immune system of bivalves, compared to mammalian immune systems, a precise description of the different mechanisms that induce its activation and functioning is still missing. In the present review, a substantial consideration will be devoted in outlining the immune responses of bivalves and their repertoire of immune cells. Finally, we will focus on the description of antimicrobial peptides that have been identified and characterized in bivalve mollusks. Their structural and antimicrobial features are also of great interest for the biotechnology sector as antimicrobial templates to combat the increasing antibiotic-resistance of different pathogenic bacteria that plague the human population all over the world. Full article

(This article belongs to the Special Issue Marine Proteins and Peptides)

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Open AccessArticle

How Environmental Factors Affect the Production of Guanidine Alkaloids by the Mediterranean Sponge Crambe crambe

by Eva Ternon, Erica Perino, Renata Manconi, Roberto Pronzato and Olivier P. Thomas

Mar. Drugs 2017, 15(6), 181; https://doi.org/10.3390/md15060181 - 16 Jun 2017

Cited by 10 | Viewed by 4415

Abstract

Most marine sponges are known to produce a large array of low molecular-weight metabolites which have applications in the pharmaceutical industry. The production of so-called specialized metabolites may be closely related to environmental factors. In this context, assessing the contribution of factors like [...] Read more.

Most marine sponges are known to produce a large array of low molecular-weight metabolites which have applications in the pharmaceutical industry. The production of so-called specialized metabolites may be closely related to environmental factors. In this context, assessing the contribution of factors like temperature, nutrients or light to the metabolomes of sponges provides relevant insights into their chemical ecology as well as the supply issue of natural sponge products. The sponge Crambe crambe was chosen as a model due to its high content of specialized metabolites belonging to polycyclic guanidine alkaloids (PGA). First results were obtained with field data of both wild and farmed specimens collected in two seasons and geographic areas of the North-Western Mediterranean. Then, further insights into factors responsible for changes in the metabolism were gained with sponges cultivated under controlled conditions in an aquarium. Comparative metabolomics showed a clear influence of the seasons and to a lesser extent of the geography while no effect of depth or farming was observed. Interestingly, sponge farming did not limit the production of PGA, while ex situ experiments did not show significant effects of several abiotic factors on the specialized metabolome at a one-month time scale. Some hypotheses were finally proposed to explain the very limited variations of PGA in C. crambe placed under different environmental conditions. Full article

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Open AccessArticle

Production of Chitin from Penaeus vannamei By-Products to Pilot Plant Scale Using a Combination of Enzymatic and Chemical Processes and Subsequent Optimization of the Chemical Production of Chitosan by Response Surface Methodology

by José A. Vázquez, Patrícia Ramos, Jesús Mirón, Jesus Valcarcel, Carmen G. Sotelo and Ricardo I. Pérez-Martín

Mar. Drugs 2017, 15(6), 180; https://doi.org/10.3390/md15060180 - 16 Jun 2017

Cited by 47 | Viewed by 7503

Abstract

The waste generated from shrimp processing contains valuable materials such as protein, carotenoids, and chitin. The present study describes a process at pilot plant scale to recover chitin from the cephalothorax of Penaeus vannamei using mild conditions. The application of a sequential enzymatic–acid–alkaline [...] Read more.

The waste generated from shrimp processing contains valuable materials such as protein, carotenoids, and chitin. The present study describes a process at pilot plant scale to recover chitin from the cephalothorax of Penaeus vannamei using mild conditions. The application of a sequential enzymatic–acid–alkaline treatment yields 30% chitin of comparable purity to commercial sources. Effluents from the process are rich in protein and astaxanthin, and represent inputs for further by-product recovery. As a last step, chitin is deacetylated to produce chitosan; the optimal conditions are established by applying a response surface methodology (RSM). Under these conditions, deacetylation reaches 92% as determined by Proton Nuclear Magnetic Resonance (¹H-NMR), and the molecular weight (Mw) of chitosan is estimated at 82 KDa by gel permeation chromatography (GPC). Chitin and chitosan microstructures are characterized by Scanning Electron Microscopy (SEM). Full article

(This article belongs to the Special Issue Marine Chitin)

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Open AccessArticle

The Roles of Spinochromes in Four Shallow Water Tropical Sea Urchins and Their Potential as Bioactive Pharmacological Agents

by Lola Brasseur, Elise Hennebert, Laurence Fievez, Guillaume Caulier, Fabrice Bureau, Lionel Tafforeau, Patrick Flammang, Pascal Gerbaux and Igor Eeckhaut

Mar. Drugs 2017, 15(6), 179; https://doi.org/10.3390/md15060179 - 16 Jun 2017

Cited by 49 | Viewed by 6247

Abstract

Spinochromes are principally known to be involved in sea urchin pigmentation as well as for their potentially interesting pharmacological properties. To assess their biological role in sea urchin physiology, experiments are undertaken on crude extracts from four species and on four isolated spinochromes [...] Read more.

Spinochromes are principally known to be involved in sea urchin pigmentation as well as for their potentially interesting pharmacological properties. To assess their biological role in sea urchin physiology, experiments are undertaken on crude extracts from four species and on four isolated spinochromes in order to test their antibacterial, antioxidant, inflammatory and cytotoxic activities. First, the antibacterial assays show that the use of crude extracts as representatives of antibacterial effects of spinochromes are inaccurate. The assays on purified spinochromes showed a decrease in the growth of four strains with an intensity depending on the spinochromes/bacteria system, revealing the participation of spinochromes in the defense system against microorganisms. Secondly, in the 2,2-diphenyl-1-picrylhydrazyl antioxidant assays, spinochromes show an enhanced activity compared to the positive control. This latter observation suggests their involvement in ultraviolet radiation protection. Third, spinochromes present a pro-inflammatory effect on lipopolysaccharide-stimulated macrophages, highlighting their possible implication in the sea urchin immune system. Finally, cytotoxicity assays based on Trypan blue exclusion, performed in view of their possible future applications as drugs, show a weak cytotoxicity of these compounds against human cells. In conclusion, all results confirm the implication of spinochromes in sea urchin defense mechanisms against their external environment and reveal their potential for pharmacological and agronomical industries. Full article

(This article belongs to the Special Issue Bioactive Marine Natural Compounds with Heterocyclic Motifs in their Structure)

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Open AccessArticle

Chondroitin Sulfate-Rich Extract of Skate Cartilage Attenuates Lipopolysaccharide-Induced Liver Damage in Mice

by Yeong Ok Song, Mijeong Kim, Minji Woo, Jang-Mi Baek, Keon-Hee Kang, Sang-Ho Kim, Seong-Soo Roh, Chan Hum Park, Kap-Seop Jeong and Jeong-Sook Noh

Mar. Drugs 2017, 15(6), 178; https://doi.org/10.3390/md15060178 - 15 Jun 2017

Cited by 20 | Viewed by 5426

Abstract

The protective effects of a chondroitin sulfate-rich extract (CSE) from skate cartilage against lipopolysaccharide (LPS)-induced hepatic damage were investigated, and its mechanism of action was compared with that of chondroitin sulfate (CS) from shark cartilage. ICR mice were orally administrated 200 mg/kg body [...] Read more.

The protective effects of a chondroitin sulfate-rich extract (CSE) from skate cartilage against lipopolysaccharide (LPS)-induced hepatic damage were investigated, and its mechanism of action was compared with that of chondroitin sulfate (CS) from shark cartilage. ICR mice were orally administrated 200 mg/kg body weight (BW) of CS or 400 mg/kg BW of CSE for 3 consecutive days, followed by a one-time intraperitoneal injection of LPS (20 mg/kg BW). The experimental groups were vehicle treatment without LPS injection (NC group), vehicle treatment with LPS injection (LPS group), CS pretreatment with LPS injection (CS group), and CSE pretreatment with LPS injection (CSE group). Hepatic antioxidant enzyme expression levels in the CS and CSE groups were increased relative to those in the LPS group. In LPS-insulted hepatic tissue, inflammatory factors were augmented relative to those in the NC group, but were significantly suppressed by pretreatment with CS or CSE. Moreover, CS and CSE alleviated the LPS-induced apoptotic factors and mitogen-activated protein kinase (MAPK). In addition, CS and CSE effectively decreased the serum lipid concentrations and downregulated hepatic sterol regulatory element-binding proteins expression. In conclusion, the skate CSE could protect against LPS-induced hepatic dyslipidemia, oxidative stress, inflammation, and apoptosis, probably through the regulation of MAPK signaling. Full article

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Open AccessArticle

Crellasterones A and B: A-Norsterol Derivatives from the New Caledonian Sponge Crella incrustans

by Kavita Ragini, Andrew M. Piggott and Peter Karuso

Mar. Drugs 2017, 15(6), 177; https://doi.org/10.3390/md15060177 - 15 Jun 2017

Cited by 11 | Viewed by 4599

Abstract

Two new steroids, crellasterones A (1) and B (2), together with the previously reported compound chalinasterol (3) and several nucleosides (4–7), were isolated from the sponge Crella incrustans, collected in New Caledonia. [...] Read more.

Two new steroids, crellasterones A (1) and B (2), together with the previously reported compound chalinasterol (3) and several nucleosides (4–7), were isolated from the sponge Crella incrustans, collected in New Caledonia. The structures of the new compounds were established by extensive NMR and mass spectroscopic analysis and revealed unprecedented marine natural products with a ring-contracted A-norsterone nucleus and 2-hydroxycyclopentenone chromophore. The absolute configurations were derived from electronic circular dichroism (ECD) measurements in conjunction with high-level density functional theory (DFT) calculations. Full article

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Open AccessReview

Off the Shelf Fouling Management

by Daniel Rittschof

Mar. Drugs 2017, 15(6), 176; https://doi.org/10.3390/md15060176 - 14 Jun 2017

Cited by 4 | Viewed by 3515

Abstract

This chapter tells the story of a research thread that identified and modified a pharmaceutical that could be a component of environmentally benign fouling management coatings. First, I present the background context of biofouling and how fouling is managed. The major target of [...] Read more.

This chapter tells the story of a research thread that identified and modified a pharmaceutical that could be a component of environmentally benign fouling management coatings. First, I present the background context of biofouling and how fouling is managed. The major target of the research is disrupting transduction of a complex process in all macrofouling organisms: metamorphosis. Using a bioassay directed approach we first identified a pharmaceutical candidate. Then, based on structure function studies coupled with laboratory and field bioassays, we simplified the molecule, eliminating halogens and aromatic rings to a pharmacophore that could be readily broken down by bacteria. Next, we did further structure function studies coupled to lab and field bioassays of modifications that enabled delivery of the molecule in a variety of coatings. The outcome is a different way of thinking about managing fouling and concepts in which molecules are designed to perform a function and then degrade. This work is discussed in the context of existing fouling management approaches and business models which use long-lived broad-spectrum biocides which have consequences for human, environmental health, and food security. Full article

(This article belongs to the Special Issue Antifouling Marine Natural Products)

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Open AccessArticle

A Novel Exopolysaccharide with Metal Adsorption Capacity Produced by a Marine Bacterium Alteromonas sp. JL2810

by Zilian Zhang, Ruanhong Cai, Wenhui Zhang, Yingnan Fu and Nianzhi Jiao

Mar. Drugs 2017, 15(6), 175; https://doi.org/10.3390/md15060175 - 12 Jun 2017

Cited by 67 | Viewed by 6063

Abstract

Most marine bacteria can produce exopolysaccharides (EPS). However, very few structures of EPS produced by marine bacteria have been determined. The characterization of EPS structure is important for the elucidation of their biological functions and ecological roles. In this study, the structure of [...] Read more.

Most marine bacteria can produce exopolysaccharides (EPS). However, very few structures of EPS produced by marine bacteria have been determined. The characterization of EPS structure is important for the elucidation of their biological functions and ecological roles. In this study, the structure of EPS produced by a marine bacterium, Alteromonas sp. JL2810, was characterized, and the biosorption of the EPS for heavy metals Cu²⁺, Ni²⁺, and Cr⁶⁺ was also investigated. Nuclear magnetic resonance (NMR) analysis indicated that the JL2810 EPS have a novel structure consisting of the repeating unit of [-3)-α-Rhap-(1→3)-α-Manp-(1→4)-α-3OAc-GalAp-(1→]. The biosorption of the EPS for heavy metals was affected by a medium pH; the maximum biosorption capacities for Cu²⁺ and Ni²⁺ were 140.8 ± 8.2 mg/g and 226.3 ± 3.3 mg/g at pH 5.0; however, for Cr⁶⁺ it was 215.2 ± 5.1 mg/g at pH 5.5. Infrared spectrometry analysis demonstrated that the groups of O-H, C=O, and C-O-C were the main function groups for the adsorption of JL2810 EPS with the heavy metals. The adsorption equilibrium of JL2810 EPS for Ni²⁺ was further analyzed, and the equilibrium data could be better represented by the Langmuir isotherm model. The novel EPS could be potentially used in industrial applications as a novel bio-resource for the removal of heavy metals. Full article

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Open AccessArticle

Effect of Supercritical Carbon Dioxide Extraction Parameters on the Biological Activities and Metabolites Present in Extracts from Arthrospira platensis

by Diego A. Esquivel-Hernández, José Rodríguez-Rodríguez, Sara P. Cuéllar-Bermúdez, J. Saúl García-Pérez, Elena I. Mancera-Andrade, Jade E. Núñez-Echevarría, Aura Ontiveros-Valencia, Magdalena Rostro-Alanis, Rebeca M. García-García, J. Antonio Torres, Wei Ning Chen and Roberto Parra-Saldívar

Mar. Drugs 2017, 15(6), 174; https://doi.org/10.3390/md15060174 - 12 Jun 2017

Cited by 29 | Viewed by 6208

Abstract

Arthrospira platensis was used to obtain functional extracts through supercritical carbon dioxide extraction (SFE-CO₂). Pressure (P), temperature (T), co-solvent (CX), static extraction (SX), dispersant (Di) and dynamic extraction (DX) were evaluated as process parameters through a Plackett–Burman design. The maximum extract [...] Read more.

Arthrospira platensis was used to obtain functional extracts through supercritical carbon dioxide extraction (SFE-CO₂). Pressure (P), temperature (T), co-solvent (CX), static extraction (SX), dispersant (Di) and dynamic extraction (DX) were evaluated as process parameters through a Plackett–Burman design. The maximum extract yield obtained was 7.48 ± 0.15% w/w. The maximum contents of bioactive metabolites in extracts were 0.69 ± 0.09 µg/g of riboflavin, 5.49 ± 0.10 µg/g of α-tocopherol, 524.46 ± 0.10 µg/g of β-carotene, 1.44 ± 0.10 µg/g of lutein and 32.11 ± 0.12 mg/g of fatty acids with 39.38% of palmitic acid, 20.63% of linoleic acid and 30.27% of γ-linolenic acid. A. platensis extracts had an antioxidant activity of 76.47 ± 0.71 µg GAE/g by Folin–Ciocalteu assay, 0.52 ± 0.02, 0.40 ± 0.01 and 1.47 ± 0.02 µmol TE/g by DPPH, FRAP and TEAC assays, respectively. These extracts showed antimicrobial activity against Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922 and Candida albicans ATCC 10231. Overall, co-solvent was the most significant factor for all measured effects (p < 0.05). Arthrospira platensis represents a sustainable source of bioactive compounds through SFE using the following extraction parameters P: 450 bar, CX: 11 g/min, SX: 15 min, DX: 25 min, T: 60 °C and Di: 35 g. Full article

(This article belongs to the Special Issue Bioactive Compounds from Marine Microbes - II)

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Open AccessReview

Marine Sponges and Bacteria as Challenging Sources of Enzyme Inhibitors for Pharmacological Applications

by Nadia Ruocco, Susan Costantini, Flora Palumbo and Maria Costantini

Mar. Drugs 2017, 15(6), 173; https://doi.org/10.3390/md15060173 - 12 Jun 2017

Cited by 24 | Viewed by 6093

Abstract

Enzymes play key roles in different cellular processes, for example, in signal transduction, cell differentiation and proliferation, metabolic processes, DNA damage repair, apoptosis, and response to stress. A deregulation of enzymes has been considered one of the first causes of several diseases, including [...] Read more.

Enzymes play key roles in different cellular processes, for example, in signal transduction, cell differentiation and proliferation, metabolic processes, DNA damage repair, apoptosis, and response to stress. A deregulation of enzymes has been considered one of the first causes of several diseases, including cancers. In the last several years, enzyme inhibitors, being good candidates as drugs in the pathogenic processes, have received an increasing amount of attention for their potential application in pharmacology. The marine environment is considered a challenging source of enzyme inhibitors for pharmacological applications. In this review, we report on secondary metabolites with enzyme inhibitory activity, focusing our attention on marine sponges and bacteria as promising sources. In the case of sponges, we only reported the kinase inhibitors, because this class was the most representative isolated so far from these marine organisms. Full article

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Open AccessReview

The Understanding of the Metazoan Skeletal System, Based on the Initial Discoveries with Siliceous and Calcareous Sponges

by Werner E. G. Müller, Heinz C. Schröder and Xiaohong Wang

Mar. Drugs 2017, 15(6), 172; https://doi.org/10.3390/md15060172 - 12 Jun 2017

Cited by 12 | Viewed by 7422

Abstract

Initiated by studies on the mechanism of formation of the skeletons of the evolutionary oldest still extant multicellular animals, the sponges (phylum Porifera) have provided new insights into the mechanism of formation of the Ca-phosphate/hydroxyapatite skeleton of vertebrate bone. Studies on the formation [...] Read more.

Initiated by studies on the mechanism of formation of the skeletons of the evolutionary oldest still extant multicellular animals, the sponges (phylum Porifera) have provided new insights into the mechanism of formation of the Ca-phosphate/hydroxyapatite skeleton of vertebrate bone. Studies on the formation of the biomineral skeleton of sponges revealed that both the formation of the inorganic siliceous skeletons (sponges of the class of Hexactinellida and Demospongiae) and of the calcareous skeletons (class of Calcarea) is mediated by enzymes (silicatein: polymerization of biosilica; and carbonic anhydrase: deposition of Ca-carbonate). Detailed studies of the initial mineralization steps in human bone-forming cells showed that this process is also controlled by enzymes, starting with the deposition of Ca-carbonate bio-seeds, mediated by carbonic anhydrases-II and -IX, followed by non-enzymatic transformation of the formed amorphous Ca-carbonate deposits into amorphous Ca-phosphate and finally hydroxyapatite crystals. The required phosphate is provided by enzymatic (alkaline phosphatase-mediated) degradation of an inorganic polymer, polyphosphate (polyP), which also acts as a donor for chemically useful energy in this process. These new discoveries allow the development of novel biomimetic strategies for treatment of bone diseases and defects. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology II 2016)

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Open AccessArticle

Application of Computational Chemical Shift Prediction Techniques to the Cereoanhydride Structure Problem—Carboxylate Complications

by Carla M. Saunders and Dean J. Tantillo

Mar. Drugs 2017, 15(6), 171; https://doi.org/10.3390/md15060171 - 12 Jun 2017

Cited by 7 | Viewed by 3982

Abstract

Despite the vast array of techniques available to modern-day chemists, structural misassignments still occur. These misassignments are often only realized upon attempted synthesis, when the spectra of synthesized products do not match previously reported spectra. This was the case with marine natural product [...] Read more.

Despite the vast array of techniques available to modern-day chemists, structural misassignments still occur. These misassignments are often only realized upon attempted synthesis, when the spectra of synthesized products do not match previously reported spectra. This was the case with marine natural product cereoanhydride. The originally proposed 7-membered ring anhydride (1) was shown to be incorrect, although a likely precursor to the correct structure (2) in both its laboratory synthesis and biosynthesis. Herein, in addition to showing how NMR computations could have been used to arrive at the correct structure, we show that the conversion of 1 to 2 is indeed energetically viable, and we highlight complications in predicting NMR chemical shifts for molecules with acidic protons. Full article

(This article belongs to the Special Issue Structural Techniques in Natural Products Drug Discovery)

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Open AccessArticle

Identification of a Novel O-Conotoxin Reveals an Unusual and Potent Inhibitor of the Human α9α10 Nicotinic Acetylcholine Receptor

by Shantong Jiang, Han-Shen Tae, Shaoqiong Xu, Xiaoxia Shao, David J. Adams and Chunguang Wang

Mar. Drugs 2017, 15(6), 170; https://doi.org/10.3390/md15060170 - 9 Jun 2017

Cited by 19 | Viewed by 4213

Abstract

Conotoxins are a pool of disulfide-rich peptide neurotoxins produced by cone snails for predation and defense. They are a rich reservoir of novel ligands for ion channels, neurotransmitter receptors and transporters in the nervous system. In this study, we identified a novel conotoxin [...] Read more.

Conotoxins are a pool of disulfide-rich peptide neurotoxins produced by cone snails for predation and defense. They are a rich reservoir of novel ligands for ion channels, neurotransmitter receptors and transporters in the nervous system. In this study, we identified a novel conotoxin component, O-conotoxin GeXXVIIA, from the venom of Conus generalis. The native form of this component is a disulfide-linked homodimer of a 5-Cys-containing peptide. Surprisingly, our electrophysiological studies showed that, in comparison to the folded monomers, the linear peptide of this toxin had the highest inhibitory activity at the human α9α10 nicotinic acetylcholine receptor (nAChR), with an IC₅₀ of 16.2 ± 1.4 nM. The activities of the N-terminal and C-terminal halves of the linear toxin are markedly reduced compared with the full-length toxin, suggesting that the intact sequence is required to potently inhibit the hα9α10 nAChR. α9α10 nAChRs are expressed not only in the nervous system, but also in a variety of non-neuronal cells, such as cochlear hair cells, keratinocytes, epithelial and immune cells. A potent inhibitor of human α9α10 nAChRs, such as GeXXVIIA, would facilitate unraveling the functions of this nAChR subtype. Furthermore, this unusual nAChR inhibitor may lead to the development of novel α9α10 nAChR-targeting drugs. Full article

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Open AccessArticle

Trichodermanins C–E, New Diterpenes with a Fused 6-5-6-6 Ring System Produced by a Marine Sponge-Derived Fungus

by Takeshi Yamada, Mayo Suzue, Takanobu Arai, Takashi Kikuchi and Reiko Tanaka

Mar. Drugs 2017, 15(6), 169; https://doi.org/10.3390/md15060169 - 9 Jun 2017

Cited by 25 | Viewed by 4310

Abstract

Trichodermanins C–E (1–3), new diterpenes with a rare fused 6-5-6-6 ring system, have been isolated from a fungus Trichoderma harzianum OUPS-111D-4 separated from a piece of a marine sponge Halichondria okadai, and these chemical structures have been established [...] Read more.

Trichodermanins C–E (1–3), new diterpenes with a rare fused 6-5-6-6 ring system, have been isolated from a fungus Trichoderma harzianum OUPS-111D-4 separated from a piece of a marine sponge Halichondria okadai, and these chemical structures have been established by spectroscopic analyses using IR, MASS, HRFABMS, and NMR spectra. We established their absolute stereostructures by application of the modified Mosher’s method. In addition, 1 inhibited the growth of cancer cell lines potently. Full article

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Open AccessArticle

Higher Anti-Liver Fibrosis Effect of Cordyceps militaris-Fermented Product Cultured with Deep Ocean Water via Inhibiting Proinflammatory Factors and Fibrosis-Related Factors Expressions

by Yu-Ping Hung and Chun-Lin Lee

Mar. Drugs 2017, 15(6), 168; https://doi.org/10.3390/md15060168 - 8 Jun 2017

Cited by 18 | Viewed by 5850

Abstract

Deep ocean water (DOW) has been shown to enhance the functional components of fungi, resulting in increased health benefits. Therefore, using DOW for culturing fungi can enhance the cordycepin and adenosine of Cordyceps militaris (CM) and its protective effects on the liver. In [...] Read more.

Deep ocean water (DOW) has been shown to enhance the functional components of fungi, resulting in increased health benefits. Therefore, using DOW for culturing fungi can enhance the cordycepin and adenosine of Cordyceps militaris (CM) and its protective effects on the liver. In this study, the antiliver fibrosis effects and mechanisms of ultrapure water-cultured CM (UCM), DOW-cultured CM (DCM), synthetic water-cultured CM, DOW, cordycepin, and adenosine were compared in the liver fibrosis mice induced by intraperitoneal injections of thioacetamide (TAA). The results indicated that DCM exhibited superior performance in reducing liver collagen accumulation, mitigating liver injuries, inhibiting proinflammatory factors and fibrosis-related factor (TGF-β1, Smad2/3, α-SMA, COL1A1) expression compared with UCM. DOW, cordycepin, and adenosine also performed antiliver fibrosis effect. Therefore, because DCM is rich in DOW and functional components, it can achieve anti-liver fibrosis effects through multiple pathways. These ameliorative effects are considerably superior to those of UCM. Full article

(This article belongs to the Special Issue Marine Compounds and Inflammation II, 2017)

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Open AccessArticle

Synergistic Antibacterial Effects of Chitosan-Caffeic Acid Conjugate against Antibiotic-Resistant Acne-Related Bacteria

by Ji-Hoon Kim, Daeung Yu, Sung-Hwan Eom, Song-Hee Kim, Junghwan Oh, Won‐Kyo Jung and Young-Mog Kim

Mar. Drugs 2017, 15(6), 167; https://doi.org/10.3390/md15060167 - 8 Jun 2017

Cited by 66 | Viewed by 7295

Abstract

The object of this study was to discover an alternative therapeutic agent with fewer side effects against acne vulgaris, one of the most common skin diseases. Acne vulgaris is often associated with acne-related bacteria such as Propionibacterium acnes, Staphylococcus epidermidis, Staphylococcus [...] Read more.

The object of this study was to discover an alternative therapeutic agent with fewer side effects against acne vulgaris, one of the most common skin diseases. Acne vulgaris is often associated with acne-related bacteria such as Propionibacterium acnes, Staphylococcus epidermidis, Staphylococcus aureus, and Pseudomonas aeruginosa. Some of these bacteria exhibit a resistance against commercial antibiotics that have been used in the treatment of acne vulgaris (tetracycline, erythromycin, and lincomycin). In the current study, we tested in vitro antibacterial effect of chitosan-phytochemical conjugates on acne-related bacteria. Three chitosan-phytochemical conjugates used in this study exhibited stronger antibacterial activity than that of chitosan (unmodified control). Chitosan-caffeic acid conjugate (CCA) showed the highest antibacterial effect on acne-related bacteria along with minimum inhibitory concentration (MIC; 8 to 256 μg/mL). Additionally, the MIC values of antibiotics against antibiotic-resistant P. acnes and P. aeruginosa strains were dramatically reduced in combination with CCA, suggesting that CCA would restore the antibacterial activity of the antibiotics. The analysis of fractional inhibitory concentration (FIC) indices clearly revealed a synergistic antibacterial effect of CCA with antibiotics. Thus, the median sum of FIC (∑FIC) values against the antibiotic-resistant bacterial strains ranged from 0.375 to 0.533 in the combination mode of CCA and antibiotics. The results of the present study suggested a potential possibility of chitosan-phytochemical conjugates in the control of infections related to acne vulgaris. Full article

(This article belongs to the Special Issue Antibacterial Marine Pharmacology)

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Borrelidins C–E: New Antibacterial Macrolides from a Saltern-Derived Halophilic Nocardiopsis sp.

by Jungwoo Kim, Daniel Shin, Seong-Hwan Kim, Wanki Park, Yoonho Shin, Won Kyung Kim, Sang Kook Lee, Ki-Bong Oh, Jongheon Shin and Dong-Chan Oh

Mar. Drugs 2017, 15(6), 166; https://doi.org/10.3390/md15060166 - 6 Jun 2017

Cited by 42 | Viewed by 5458

Abstract

Chemical investigation of a halophilic actinomycete strain belonging to the genus Nocardiopsis inhabiting a hypersaline saltern led to the discovery of new 18-membered macrolides with nitrile functionality, borrelidins C–E (1–3), along with a previously reported borrelidin (4). [...] Read more.

Chemical investigation of a halophilic actinomycete strain belonging to the genus Nocardiopsis inhabiting a hypersaline saltern led to the discovery of new 18-membered macrolides with nitrile functionality, borrelidins C–E (1–3), along with a previously reported borrelidin (4). The planar structures of borrelidins C–E, which are new members of the rare borrelidin class of antibiotics, were elucidated by NMR, mass, IR, and UV spectroscopic analyses. The configurations of borrelidines C–E were determined by the interpretation of ROESY NMR spectra, J-based configuration analysis, a modified Mosher’s method, and CD spectroscopic analysis. Borrelidins C and D displayed inhibitory activity, particularly against the Gram-negative pathogen Salmonella enterica, and moderate cytotoxicity against the SNU638 and K562 carcinoma cell lines. Full article

(This article belongs to the Special Issue Antibacterial Marine Pharmacology)

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Open AccessReview

Interpreting Microbial Biosynthesis in the Genomic Age: Biological and Practical Considerations

by Ian J. Miller, Marc G. Chevrette and Jason C. Kwan

Mar. Drugs 2017, 15(6), 165; https://doi.org/10.3390/md15060165 - 6 Jun 2017

Cited by 20 | Viewed by 7850

Abstract

Genome mining has become an increasingly powerful, scalable, and economically accessible tool for the study of natural product biosynthesis and drug discovery. However, there remain important biological and practical problems that can complicate or obscure biosynthetic analysis in genomic and metagenomic sequencing projects. [...] Read more.

Genome mining has become an increasingly powerful, scalable, and economically accessible tool for the study of natural product biosynthesis and drug discovery. However, there remain important biological and practical problems that can complicate or obscure biosynthetic analysis in genomic and metagenomic sequencing projects. Here, we focus on limitations of available technology as well as computational and experimental strategies to overcome them. We review the unique challenges and approaches in the study of symbiotic and uncultured systems, as well as those associated with biosynthetic gene cluster (BGC) assembly and product prediction. Finally, to explore sequencing parameters that affect the recovery and contiguity of large and repetitive BGCs assembled de novo, we simulate Illumina and PacBio sequencing of the Salinispora tropica genome focusing on assembly of the salinilactam (slm) BGC. Full article

(This article belongs to the Special Issue Connecting Marine Microbial Natural Products to Biosynthetic Pathways)

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Open AccessArticle

A Novel Lid-Covering Peptide Inhibitor of Nicotinic Acetylcholine Receptors Derived from αD-Conotoxin GeXXA

by Longjin Yang, Han-Shen Tae, Zhou Fan, Xiaoxia Shao, Shaoqiong Xu, Suwen Zhao, David J. Adams and Chunguang Wang

Mar. Drugs 2017, 15(6), 164; https://doi.org/10.3390/md15060164 - 5 Jun 2017

Cited by 10 | Viewed by 6500

Abstract

Nicotinic acetylcholine receptors (nAChRs) play a fundamental role in nervous signal transmission, therefore various antagonists and agonists are highly desired to explore the structure and function of nAChRs. Recently, a novel dimeric αD-conotoxin GeXXA was identified to inhibit nAChRs by binding at the [...] Read more.

Nicotinic acetylcholine receptors (nAChRs) play a fundamental role in nervous signal transmission, therefore various antagonists and agonists are highly desired to explore the structure and function of nAChRs. Recently, a novel dimeric αD-conotoxin GeXXA was identified to inhibit nAChRs by binding at the top surface of the receptors, and the monomeric C-terminal domain (CTD) of αD-GeXXA retains some inhibitory activity. In this study, the internal dimeric N-terminal domain (NTD) of this conopeptide was further investigated. We first developed a regio-selective protection strategy to chemically prepare the anti-parallel dimeric NTD, and found that the isolated NTD part of GeXXA possesses the nAChR-inhibitory activity, the subtype-dependence of which implies a preferred binding of NTD to the β subunits of nAChR. Deletion of the NTD N-terminal residues did not affect the activity of NTD, indicating that the N-terminus is not involved in the interaction with nAChRs. By optimizing the sequence of NTD, we obtained a fully active single-chain cyclic NTD, based on which 4 Arg residues were found to interact with nAChRs. These results demonstrate that the NTD part of αD-GeXXA is a “lid-covering” nAChR inhibitor, displaying a novel inhibitory mechanism distinct from other allosteric ligands of nAChRs. Full article

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Open AccessArticle

Xyloketal B Attenuates Fatty Acid-Induced Lipid Accumulation via the SREBP-1c Pathway in NAFLD Models

by Youying Zhang, Tian Meng, Ling Zuo, Yu Bei, Qihao Zhang, Zhijian Su, Yadong Huang, Jiyan Pang, Qi Xiang and Hongtu Yang

Mar. Drugs 2017, 15(6), 163; https://doi.org/10.3390/md15060163 - 3 Jun 2017

Cited by 38 | Viewed by 5523

Abstract

The goal of this study was to examine the effects of xyloketal B on nonalcoholic fatty liver disease (NAFLD) and to explore the molecular mechanisms underlying its effects in both in vivo and in vitro models. We discovered an association between xyloketal B [...] Read more.

The goal of this study was to examine the effects of xyloketal B on nonalcoholic fatty liver disease (NAFLD) and to explore the molecular mechanisms underlying its effects in both in vivo and in vitro models. We discovered an association between xyloketal B and the sterol regulatory element-binding protein-1c (SREBP-1c) signaling pathway, which is related to lipid metabolism. Mice were dosed with xyloketal B (5, 10 and 20 mg/kg/d) and atorvastatin (15 mg/kg/d) via intraperitoneal injection once daily for 40 days after being fed a high fat diet plus 10% high fructose liquid (HFD+HFL) for 8 weeks. Xyloketal B significantly improved HFD+HFL-induced hepatic histological lesions and attenuated lipid and glucose accumulation in the blood as well as lipid accumulation in the liver. Xyloketal B increased the expression of CPT1A, and decreased the expression of SREBP-1c and its downstream targeting enzymes such as ACC1, ACL, and FAS. Xyloketal B also significantly reduced lipid accumulation in HepG2 cells treated with free fatty acids (FFAs). These data suggested that xyloketal B has lipid-lowering effects via the SREBP-1c pathway that regulate lipid metabolism. Thus, targeting SREBP-1c activation with xyloketal B may be a promising novel approach for NAFLD treatment. Full article

(This article belongs to the Special Issue Selected Papers from the International Conference on Coastal Ecology and Marine Biotechnology Dec. 8-10, 2016 Bangkok, Thailand)

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