Marine Drugs

21 pages, 3859 KiB

Open AccessArticle

Cyanobacteria as Nanogold Factories: Chemical and Anti-Myocardial Infarction Properties of Gold Nanoparticles Synthesized by Lyngbya majuscula

by Esam M. Bakir, Nancy S. Younis, Maged E. Mohamed and Nermin A. El Semary

Mar. Drugs 2018, 16(6), 217; https://doi.org/10.3390/md16060217 - 20 Jun 2018

Cited by 80 | Viewed by 6054

Abstract

To the best of our knowledge, cyanobacterial strains from the Arabian Gulf have never been investigated with respect to their potential for nanoparticle production. Lyngbya majuscula was isolated from the AlOqair area, Al-Ahsa Government, Eastern Province, Kingdom of Saudi Arabia. The cyanobacterium was [...] Read more.

To the best of our knowledge, cyanobacterial strains from the Arabian Gulf have never been investigated with respect to their potential for nanoparticle production. Lyngbya majuscula was isolated from the AlOqair area, Al-Ahsa Government, Eastern Province, Kingdom of Saudi Arabia. The cyanobacterium was initially incubated with 1500 mg/mL of HAuCl₄ for two days. The blue-green strain turned purple, which indicated the intracellular formation of gold nanoparticles. Prolonged incubation for over two months triggered the extracellular production of nanogold particles. UV-visible spectroscopy measurements indicated the presence of a resonance plasmon band at ~535 nm, whereas electron microscopy scanning indicated the presence of gold nanoparticles with an average diameter of 41.7 ± 0.2 nm. The antioxidant and anti-myocardial infarction activities of the cyanobacterial extract, the gold nanoparticle solution, and a combination of both were investigated in animal models. Isoproterenol (100 mg/kg, SC (sub cutaneous)) was injected into experimental rats for three days to induce a state of myocardial infarction; then the animals were given cyanobacterial extract (200 mg/kg/day, IP (intra peritoneal)), gold nanoparticles (200 mg/kg/day, IP), ora mixture of both for 14 days. Cardiac biomarkers, electrocardiogram (ECG), blood pressure, and antioxidant enzymes were determined as indicators of myocardial infarction. The results showed that isoproterenol elevates ST and QT segments and increases heart rate and serum activities of creatine phosphokinase (CPK), creatine kinase-myocardial bound (CP-MB), and cardiac troponin T (cTnT). It also reduces heart tissue content of glutathione peroxidase (GRx) and superoxide dismutase (SOD), and the arterial pressure indices of systolic arterial pressure (SAP), diastolic arterial pressure (DAP), and mean arterial pressure (MAP). Gold nanoparticles alone or in combination with cyanobacterial extract produced an inhibitory effect on isoproterenol-induced changes in serum cardiac injury markers, ECG, arterial pressure indices, and antioxidant capabilities of the heart. Full article

(This article belongs to the Special Issue Compounds from Cyanobacteria II)

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13 pages, 1962 KiB

Open AccessArticle

Dietary Supplementation with a Magnesium-Rich Marine Mineral Blend Enhances the Diversity of Gastrointestinal Microbiota

by Erin K. Crowley, Caitriona M. Long-Smith, Amy Murphy, Elaine Patterson, Kiera Murphy, Denise M. O’Gorman, Catherine Stanton and Yvonne M. Nolan

Mar. Drugs 2018, 16(6), 216; https://doi.org/10.3390/md16060216 - 20 Jun 2018

Cited by 42 | Viewed by 10269

Abstract

Accumulating evidence demonstrates that dietary supplementation with functional food ingredients play a role in systemic and brain health as well as in healthy ageing. Conversely, deficiencies in calcium and magnesium as a result of the increasing prevalence of a high fat/high sugar “Western [...] Read more.

Accumulating evidence demonstrates that dietary supplementation with functional food ingredients play a role in systemic and brain health as well as in healthy ageing. Conversely, deficiencies in calcium and magnesium as a result of the increasing prevalence of a high fat/high sugar “Western diet” have been associated with health problems such as obesity, inflammatory bowel diseases, and cardiovascular diseases, as well as metabolic, immune, and psychiatric disorders. It is now recognized that modulating the diversity of gut microbiota, the population of intestinal bacteria, through dietary intervention can significantly impact upon gut health as well as systemic and brain health. In the current study, we show that supplementation with a seaweed and seawater-derived functional food ingredient rich in bioactive calcium and magnesium (0.1% supplementation) as well as 70 other trace elements, significantly enhanced the gut microbial diversity in adult male rats. Given the significant impact of gut microbiota on health, these results position this marine multi-mineral blend (MMB) as a promising digestive-health promoting functional food ingredient. Full article

(This article belongs to the Special Issue Marine Health Compounds: From Extraction to Food and Pharmaceutical Application)

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12 pages, 2901 KiB

Open AccessArticle

Effect of Methionine Oxidation and Substitution of α-Conotoxin TxID on α3β4 Nicotinic Acetylcholine Receptor

by Jie Ren, Rui Li, Jiong Ning, Xiaopeng Zhu, Dongting Zhangsun, Yong Wu and Sulan Luo

Mar. Drugs 2018, 16(6), 215; https://doi.org/10.3390/md16060215 - 20 Jun 2018

Cited by 7 | Viewed by 3937

Abstract

α-Conotoxin TxID was discovered from Conus textile by gene cloning, which has 4/6 inter-cysteine loop spacing and selectively inhibits α3β4 nicotinic acetylcholine receptor (nAChR) subtype. However, TxID is susceptible to modification due to it containing a methionine (Met) residue that easily forms methionine [...] Read more.

α-Conotoxin TxID was discovered from Conus textile by gene cloning, which has 4/6 inter-cysteine loop spacing and selectively inhibits α3β4 nicotinic acetylcholine receptor (nAChR) subtype. However, TxID is susceptible to modification due to it containing a methionine (Met) residue that easily forms methionine sulfoxide (MetO) in oxidative environment. In this study, we investigated how Met-11 and its derivatives affect the activity of TxID using a combination of electrophysiological recordings and molecular modelling. The results showed most TxID analogues had substantially decreased activities on α3β4 nAChR with more than 10-fold potency loss and 5 of them demonstrated no inhibition on α3β4 nAChR. However, one mutant, [M11I]TxID, displayed potent inhibition at α3β4 nAChR with an IC₅₀ of 69 nM, which only exhibited 3.8-fold less compared with TxID. Molecular dynamics simulations were performed to expound the decrease in the affinity for α3β4 nAChR. The results indicate replacement of Met with a hydrophobic moderate-sized Ile in TxID is an alternative strategy to reduce the impact of Met oxidation, which may help to redesign conotoxins containing methionine residue. Full article

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26 pages, 8813 KiB

Open AccessReview

Chemistry and Biological Activities of the Marine Sponges of the Genera Mycale (Arenochalina), Biemna and Clathria

by Amr El-Demerdash, Mohamed A. Tammam, Atanas G. Atanasov, John N. A. Hooper, Ali Al-Mourabit and Anake Kijjoa

Mar. Drugs 2018, 16(6), 214; https://doi.org/10.3390/md16060214 - 18 Jun 2018

Cited by 32 | Viewed by 8902

Abstract

Over the past seven decades, particularly since the discovery of the first marine-derived nucleosides, spongothymidine and spongouridine, from the Caribbean sponge Cryptotethya crypta in the early 1950s, marine natural products have emerged as unique, renewable and yet under-investigated pools for discovery of new [...] Read more.

Over the past seven decades, particularly since the discovery of the first marine-derived nucleosides, spongothymidine and spongouridine, from the Caribbean sponge Cryptotethya crypta in the early 1950s, marine natural products have emerged as unique, renewable and yet under-investigated pools for discovery of new drug leads with distinct structural features, and myriad interesting biological activities. Marine sponges are the most primitive and simplest multicellular animals, with approximately 8900 known described species, although more than 15,000 species are thought to exist worldwide today. These marine organisms potentially represent the richest pipeline for novel drug leads. Mycale (Arenochalina) and Clathria are recognized marine sponge genera belonging to the order Poecilosclerida, whereas Biemna was more recently reclassified, based on molecular genetics, as a new order Biemnida. Together, these sponge genera contribute to the production of physiologically active molecular entities with diverse structural features and a wide range of medicinal and therapeutic potentialities. In this review, we provide a comprehensive insight and up-to-date literature survey over the period of 1976–2018, focusing on the chemistry of the isolated compounds from members of these three genera, as well as their biological and pharmacological activities, whenever available. Full article

(This article belongs to the Special Issue Bioactive Compounds from Marine Sponges)

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11 pages, 2407 KiB

Open AccessArticle

Raistrickiones A−E from a Highly Productive Strain of Penicillium raistrickii Generated through Thermo Change

by De-Sheng Liu, Xian-Guo Rong, Hui-Hui Kang, Li-Ying Ma, Mark T. Hamann and Wei-Zhong Liu

Mar. Drugs 2018, 16(6), 213; https://doi.org/10.3390/md16060213 - 18 Jun 2018

Cited by 12 | Viewed by 4259

Abstract

Three new diastereomers of polyketides (PKs), raistrickiones A−C (1–3), together with two new analogues, raistrickiones D and E (4 and 5), were isolated from a highly productive strain of Penicillium raistrickii, which was subjected to an [...] Read more.

Three new diastereomers of polyketides (PKs), raistrickiones A−C (1–3), together with two new analogues, raistrickiones D and E (4 and 5), were isolated from a highly productive strain of Penicillium raistrickii, which was subjected to an experimental thermo-change strategy to tap its potential of producing new secondary metabolites. Metabolites 1 and 2 existed in a diastereomeric mixture in the crystal packing according to the X-ray data, and were laboriously separated by semi-preparative HPLC on a chiral column. The structures of 1–5 were determined on the basis of the detailed analyses of the spectroscopic data (UV, IR, HRESIMS, 1D, and 2D NMR), single-crystal X-ray diffractions, and comparison of the experimental and calculated electronic circular dichroism spectra. Compounds 1–5 represented the first case of 3,5-dihydroxy-4-methylbenzoyl derivatives of natural products. Compounds 1–5 exhibited moderate radical scavenging activities against 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH). Full article

(This article belongs to the Special Issue Bioactive Compounds from Marine-Derived Aspergillus, Penicillium, Talaromyces and Trichoderma Species)

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22 pages, 6508 KiB

Open AccessArticle

Breaking down Leukemia Walls: Heteronemin, a Sesterterpene Derivative, Induces Apoptosis in Leukemia Molt4 Cells through Oxidative Stress, Mitochondrial Dysfunction and Induction of Talin Expression

by Yu-Cheng Chen, Mei-Chin Lu, Mohamed El-Shazly, Kuei-Hung Lai, Tung-Ying Wu, Yu-Ming Hsu, Yi-Lun Lee and Yi-Chang Liu

Mar. Drugs 2018, 16(6), 212; https://doi.org/10.3390/md16060212 - 17 Jun 2018

Cited by 25 | Viewed by 5980

Abstract

Heteronemin, the most abundant secondary metabolite in the sponge Hippospongia sp., exhibited potent cytotoxic activity against several cancer cell lines. It increased the percentage of apoptotic cells and reactive oxygen species (ROS) in Molt4 cells. The use of ROS scavenger, N-acetyl cysteine [...] Read more.

Heteronemin, the most abundant secondary metabolite in the sponge Hippospongia sp., exhibited potent cytotoxic activity against several cancer cell lines. It increased the percentage of apoptotic cells and reactive oxygen species (ROS) in Molt4 cells. The use of ROS scavenger, N-acetyl cysteine (NAC), suppressed both the production of ROS from mitochondria and cell apoptosis that were induced by heteronemin treatment. Heteronemin upregulated talin and phosphorylated talin expression in Molt4 cells but it only upregulated the expression of phosphorylated talin in HEK293 cells. However, pretreatment with NAC reversed these effects. Talin siRNA reversed the activation of pro-apoptotic cleaved caspases 3 and 9. On the other hand, the downstream proteins including FAK and NF-κB (p65) were not affected. In addition, we confirmed that heteronemin directly modulated phosphorylated talin expression through ROS generation resulting in cell apoptosis, but it did not affect talin/FAK complex. Furthermore, heteronemin interfered with actin microfilament and caused morphology changes. Taken together, these findings suggest that the cytotoxic effect of heteronemin is associated with oxidative stress and induction of phosphorylated talin expression. Our results suggest that heteronemin represents an interesting candidate which can be further developed as a drug lead against leukemia. Full article

(This article belongs to the Special Issue In Vitro and In Vivo Approaches in the Driving Seat of Marine Drugs Discovery)

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19 pages, 2982 KiB

Open AccessArticle

Collagen from Cartilaginous Fish By-Products for a Potential Application in Bioactive Film Composite

by Emna Ben Slimane and Saloua Sadok

Mar. Drugs 2018, 16(6), 211; https://doi.org/10.3390/md16060211 - 15 Jun 2018

Cited by 53 | Viewed by 7305

Abstract

The acid solubilised collagen (ASC) and pepsin solubilised collagen (PSC) were extracted from the by-products (skin) of a cartilaginous fish (Mustelus mustelus). The ASC and PSC yields were 23.07% and 35.27% dry weight, respectively and were identified as collagen Type I [...] Read more.

The acid solubilised collagen (ASC) and pepsin solubilised collagen (PSC) were extracted from the by-products (skin) of a cartilaginous fish (Mustelus mustelus). The ASC and PSC yields were 23.07% and 35.27% dry weight, respectively and were identified as collagen Type I with the presence of α, β and γ chains. As revealed by the Fourier Transform Infrared (FTIR) spectra analysis, pepsin did not alter the PSC triple helix structure. Based on the various type of collagen yield, only PSC was used in combination with chitosan to produce a composite film. Such film had lower tensile strength but higher elongation at break when compared to chitosan film; and lower water solubility and lightness when compared to collagen film. Equally, FTIR spectra analysis of film composite showed the occurrence of collagen-chitosan interaction resulting in a modification of the secondary structure of collagen. Collagen-chitosan-based biofilm showed a potential UV barrier properties and antioxidant activity, which might be used as green bioactive films to preserve nutraceutical products. Full article

(This article belongs to the Special Issue Collagen from Marine Biological Source and Medical Applications)

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15 pages, 5268 KiB

Open AccessArticle

Isolation and Structure Elucidation of Cembranoids from a Dongsha Atoll Soft Coral Sarcophyton stellatum

by Atallah F. Ahmed, Yi-Wei Chen, Chiung-Yao Huang, Yen-Ju Tseng, Chi-Chen Lin, Chang-Feng Dai, Yang-Chang Wu and Jyh-Horng Sheu

Mar. Drugs 2018, 16(6), 210; https://doi.org/10.3390/md16060210 - 14 Jun 2018

Cited by 24 | Viewed by 5090

Abstract

Six new polyoxygenated cembrane-based diterpenoids, stellatumolides A–C (1–3), stellatumonins A and B (4 and 5), and stellatumonone (6), were isolated together with ten known related compounds (7–16) from the ethyl acetate [...] Read more.

Six new polyoxygenated cembrane-based diterpenoids, stellatumolides A–C (1–3), stellatumonins A and B (4 and 5), and stellatumonone (6), were isolated together with ten known related compounds (7–16) from the ethyl acetate (EtOAc) extract of soft coral Sarcophyton stellatum. The structures of the new compounds were established by extensive spectroscopic analyses, including 1D and 2D nuclear magnetic resonance (NMR) spectroscopy and data comparison with related structures. Compounds 8 and 14 were isolated from a natural source for the first time. The isolated metabolites were shown to be not cytotoxic against a limited panel of cancer cells. Compound 9 showed anti-inflammatory activity by reducing the expression of proinflammatory cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) proteins in lipopolysaccharide (LPS)-stimulated mouse leukaemic monocyte macrophage (RAW 264.7) cells. Full article

(This article belongs to the Special Issue Marine Natural Products Discovery: In Memory of Late Prof. Tatsuo Higa)

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11 pages, 2086 KiB

Open AccessReview

Marine Myxobacteria: A Few Good Halophiles

by Hanan Albataineh and D. Cole Stevens

Mar. Drugs 2018, 16(6), 209; https://doi.org/10.3390/md16060209 - 14 Jun 2018

Cited by 26 | Viewed by 6595

Abstract

Currently considered an excellent candidate source of novel chemical diversity, the existence of marine myxobacteria was in question less than 20 years ago. This review aims to serve as a roll call for marine myxobacteria and to summarize their unique features when compared [...] Read more.

Currently considered an excellent candidate source of novel chemical diversity, the existence of marine myxobacteria was in question less than 20 years ago. This review aims to serve as a roll call for marine myxobacteria and to summarize their unique features when compared to better-known terrestrial myxobacteria. Characteristics for discrimination between obligate halophilic, marine myxobacteria and halotolerant, terrestrial myxobacteria are discussed. The review concludes by highlighting the need for continued discovery and exploration of marine myxobacteria as producers of novel natural products. Full article

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23 pages, 4372 KiB

Open AccessFeature PaperReview

Neuronal Nicotinic Acetylcholine Receptor Modulators from Cone Snails

by Nikita Abraham and Richard J. Lewis

Mar. Drugs 2018, 16(6), 208; https://doi.org/10.3390/md16060208 - 13 Jun 2018

Cited by 42 | Viewed by 5722

Abstract

Marine cone snails are a large family of gastropods that have evolved highly potent venoms for predation and defense. The cone snail venom has exceptional molecular diversity in neuropharmacologically active compounds, targeting a range of receptors, ion channels, and transporters. These conotoxins have [...] Read more.

Marine cone snails are a large family of gastropods that have evolved highly potent venoms for predation and defense. The cone snail venom has exceptional molecular diversity in neuropharmacologically active compounds, targeting a range of receptors, ion channels, and transporters. These conotoxins have helped to dissect the structure and function of many of these therapeutically significant targets in the central and peripheral nervous systems, as well as unravelling the complex cellular mechanisms modulated by these receptors and ion channels. This review provides an overview of α-conotoxins targeting neuronal nicotinic acetylcholine receptors. The structure and activity of both classical and non-classical α-conotoxins are discussed, along with their contributions towards understanding nicotinic acetylcholine receptor (nAChR) structure and function. Full article

(This article belongs to the Special Issue Marine Invertebrate Toxins)

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20 pages, 2383 KiB

Open AccessArticle

The Holo-Transcriptome of the Zoantharian Protopalythoa variabilis (Cnidaria: Anthozoa): A Plentiful Source of Enzymes for Potential Application in Green Chemistry, Industrial and Pharmaceutical Biotechnology

by Jean-Étienne R. L. Morlighem, Chen Huang, Qiwen Liao, Paula Braga Gomes, Carlos Daniel Pérez, Álvaro Rossan De Brandão Prieto-da-Silva, Simon Ming-Yuen Lee and Gandhi Rádis-Baptista

Mar. Drugs 2018, 16(6), 207; https://doi.org/10.3390/md16060207 - 13 Jun 2018

Cited by 10 | Viewed by 5444

Abstract

Marine invertebrates, such as sponges, tunicates and cnidarians (zoantharians and scleractinian corals), form functional assemblages, known as holobionts, with numerous microbes. This type of species-specific symbiotic association can be a repository of myriad valuable low molecular weight organic compounds, bioactive peptides and enzymes. [...] Read more.

Marine invertebrates, such as sponges, tunicates and cnidarians (zoantharians and scleractinian corals), form functional assemblages, known as holobionts, with numerous microbes. This type of species-specific symbiotic association can be a repository of myriad valuable low molecular weight organic compounds, bioactive peptides and enzymes. The zoantharian Protopalythoa variabilis (Cnidaria: Anthozoa) is one such example of a marine holobiont that inhabits the coastal reefs of the tropical Atlantic coast and is an interesting source of secondary metabolites and biologically active polypeptides. In the present study, we analyzed the entire holo-transcriptome of P. variabilis, looking for enzyme precursors expressed in the zoantharian-microbiota assemblage that are potentially useful as industrial biocatalysts and biopharmaceuticals. In addition to hundreds of predicted enzymes that fit into the classes of hydrolases, oxidoreductases and transferases that were found, novel enzyme precursors with multiple activities in single structures and enzymes with incomplete Enzyme Commission numbers were revealed. Our results indicated the predictive expression of thirteen multifunctional enzymes and 694 enzyme sequences with partially characterized activities, distributed in 23 sub-subclasses. These predicted enzyme structures and activities can prospectively be harnessed for applications in diverse areas of industrial and pharmaceutical biotechnology. Full article

(This article belongs to the Special Issue Jellyfish and Polyps: Cnidarians as Sustainable Resources for Biotechnological Applications and Bioprospecting)

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14 pages, 4586 KiB

Open AccessArticle

Smenamide A Analogues. Synthesis and Biological Activity on Multiple Myeloma Cells

by Alessia Caso, Ilaria Laurenzana, Daniela Lamorte, Stefania Trino, Germana Esposito, Vincenzo Piccialli and Valeria Costantino

Mar. Drugs 2018, 16(6), 206; https://doi.org/10.3390/md16060206 - 13 Jun 2018

Cited by 12 | Viewed by 4731

Abstract

Smenamides are an intriguing class of peptide/polyketide molecules of marine origin showing antiproliferative activity against lung cancer Calu-1 cells at nanomolar concentrations through a clear pro-apoptotic mechanism. To probe the role of the activity-determining structural features, the 16-epi-analogue of smenamide A [...] Read more.

Smenamides are an intriguing class of peptide/polyketide molecules of marine origin showing antiproliferative activity against lung cancer Calu-1 cells at nanomolar concentrations through a clear pro-apoptotic mechanism. To probe the role of the activity-determining structural features, the 16-epi-analogue of smenamide A and eight simplified analogues in the 16-epi series were prepared using a flexible synthetic route. The synthetic analogues were tested on multiple myeloma (MM) cell lines showing that the configuration at C-16 slightly affects the activity, since the 16-epi-derivative is still active at nanomolar concentrations. Interestingly, it was found that the truncated compound 8, mainly composed of the pyrrolinone terminus, was not active, while compound 13, essentially lacking the pyrrolinone moiety, was 1000-fold less active than the intact substance and was the most active among all the synthesized compounds. Full article

(This article belongs to the Special Issue Synthetic and Biosynthetic Approaches to Marine Natural Products)

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9 pages, 1233 KiB

Open AccessArticle

Absolute Configuration Determination of Retroflexanone Using the Advanced Mosher Method and Application of HPLC-NMR

by Caleb Singleton, Robert Brkljača and Sylvia Urban

Mar. Drugs 2018, 16(6), 205; https://doi.org/10.3390/md16060205 - 12 Jun 2018

Cited by 5 | Viewed by 5099

Abstract

The absolute configuration of retroflexanone (1) and a closely related phlorogluinol (2) was established using the advanced Mosher method and by application of HPLC-NMR. HPLC-NMR permitted a small scale Mosher method analysis to be carried out on these unstable phloroglucinols. Full article

(This article belongs to the Special Issue Advances in Marine Natural Product Characterisation and Separation Methodologies)

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24 pages, 6480 KiB

Open AccessArticle

Heteronemin, a Marine Sesterterpenoid-Type Metabolite, Induces Apoptosis in Prostate LNcap Cells via Oxidative and ER Stress Combined with the Inhibition of Topoisomerase II and Hsp90

by Man-Gang Lee, Yi-Chang Liu, Yi-Lun Lee, Mohamed El-Shazly, Kuei-Hung Lai, Shou-Ping Shih, Seng-Chung Ke, Ming-Chang Hong, Ying-Chi Du, Juan-Cheng Yang, Ping-Jyun Sung, Zhi-Hong Wen and Mei-Chin Lu

Mar. Drugs 2018, 16(6), 204; https://doi.org/10.3390/md16060204 - 10 Jun 2018

Cited by 48 | Viewed by 6624

Abstract

Heteronemin, a marine sesterterpenoid-type natural product, possesses diverse bioactivities, especially antitumor effect. Accumulating evidence shows that heteronemin may act as a potent anticancer agent in clinical therapy. To fully understand the antitumor mechanism of heteronemin, we further explored the precise molecular targets in [...] Read more.

Heteronemin, a marine sesterterpenoid-type natural product, possesses diverse bioactivities, especially antitumor effect. Accumulating evidence shows that heteronemin may act as a potent anticancer agent in clinical therapy. To fully understand the antitumor mechanism of heteronemin, we further explored the precise molecular targets in prostate cancer cells. Initially, heteronemin exhibited potent cytotoxic effect against LNcap and PC3 prostate cancer cells with IC₅₀ 1.4 and 2.7 μM after 24 h, respectively. In the xenograft animal model, the tumor size was significantly suppressed to about 51.9% in the heteronemin-treated group in comparison with the control group with no significant difference in the mice body weights. In addition, the results of a cell-free system assay indicated that heteronemin could act as topoisomerase II (topo II) catalytic inhibitor through the elimination of essential enzymatic activity of topoisomerase IIα expression. We found that the use of heteronemin-triggered apoptosis by 20.1–68.3%, caused disruption of mitochondrial membrane potential (MMP) by 66.9–99.1% and promoted calcium release by 1.8-, 2.0-, and 2.1-fold compared with the control group in a dose-dependent manner, as demonstrated by annexin-V/PI, rhodamine 123 and Fluo-3 staining assays, respectively. Moreover, our findings indicated that the pretreatment of LNcap cells with an inhibitor of protein tyrosine phosphatase (PTPi) diminished growth inhibition, oxidative and Endoplasmic Reticulum (ER) stress, as well as activation of Chop/Hsp70 induced by heteronemin, suggesting PTP activation plays a crucial rule in the cytotoxic activity of heteronemin. Using molecular docking analysis, heteronemin exhibited more binding affinity to the N-terminal ATP-binding pocket of Hsp90 protein than 17-AAG, a standard Hsp90 inhibitor. Finally, heteronemin promoted autophagy and apoptosis through the inhibition of Hsp 90 and topo II as well as PTP activation in prostate cancer cells. Taken together, these multiple targets present heteronemin as an interesting candidate for its future development as an antiprostatic agent. Full article

(This article belongs to the Special Issue In Vitro and In Vivo Approaches in the Driving Seat of Marine Drugs Discovery)

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25 pages, 5540 KiB

Open AccessReview

Exploring the Valuable Carotenoids for the Large-Scale Production by Marine Microorganisms

by Javier Torregrosa-Crespo, Zaida Montero, Juan Luis Fuentes, Manuel Reig García-Galbis, Inés Garbayo, Carlos Vílchez and Rosa María Martínez-Espinosa

Mar. Drugs 2018, 16(6), 203; https://doi.org/10.3390/md16060203 - 8 Jun 2018

Cited by 118 | Viewed by 8779

Abstract

Carotenoids are among the most abundant natural pigments available in nature. These pigments have received considerable attention because of their biotechnological applications and, more importantly, due to their potential beneficial uses in human healthcare, food processing, pharmaceuticals and cosmetics. These bioactive compounds are [...] Read more.

Carotenoids are among the most abundant natural pigments available in nature. These pigments have received considerable attention because of their biotechnological applications and, more importantly, due to their potential beneficial uses in human healthcare, food processing, pharmaceuticals and cosmetics. These bioactive compounds are in high demand throughout the world; Europe and the USA are the markets where the demand for carotenoids is the highest. The in vitro synthesis of carotenoids has sustained their large-scale production so far. However, the emerging modern standards for a healthy lifestyle and environment-friendly practices have given rise to a search for natural biocompounds as alternatives to synthetic ones. Therefore, nowadays, biomass (vegetables, fruits, yeast and microorganisms) is being used to obtain naturally-available carotenoids with high antioxidant capacity and strong color, on a large scale. This is an alternative to the in vitro synthesis of carotenoids, which is expensive and generates a large number of residues, and the compounds synthesized are sometimes not active biologically. In this context, marine biomass has recently emerged as a natural source for both common and uncommon valuable carotenoids. Besides, the cultivation of marine microorganisms, as well as the downstream processes, which are used to isolate the carotenoids from these microorganisms, offer several advantages over the other approaches that have been explored previously. This review summarizes the general properties of the most-abundant carotenoids produced by marine microorganisms, focusing on the genuine/rare carotenoids that exhibit interesting features useful for potential applications in biotechnology, pharmaceuticals, cosmetics and medicine. Full article

(This article belongs to the Special Issue Marine Carotenoids)

13 pages, 2989 KiB

Open AccessArticle

Butyrolactone-I from Coral-Derived Fungus Aspergillus terreus Attenuates Neuro-Inflammatory Response via Suppression of NF-κB Pathway in BV-2 Cells

by Yuan Yuan Zhang, Yi Zhang, Yuan-Bei Yao, Xiao-Ling Lei and Zhong-Ji Qian

Mar. Drugs 2018, 16(6), 202; https://doi.org/10.3390/md16060202 - 7 Jun 2018

Cited by 28 | Viewed by 4992

Abstract

Butyrolactone-I (ZB5-1) from the coral-derived fungus Aspergillus terreus was investigated in this study to estimate its anti-neuroinflammatory effects on lipopolysaccharide (LPS)-induced BV-2 microglia cells. MTT assay indicated that ZB5-1 in tested concentrations had no cytotoxicity on BV-2 cells, and significantly reduced the production [...] Read more.

Butyrolactone-I (ZB5-1) from the coral-derived fungus Aspergillus terreus was investigated in this study to estimate its anti-neuroinflammatory effects on lipopolysaccharide (LPS)-induced BV-2 microglia cells. MTT assay indicated that ZB5-1 in tested concentrations had no cytotoxicity on BV-2 cells, and significantly reduced the production of nitric oxide (NO), measured using Griess reagent, and interleukin-1 beta (IL-1β), detected by enzyme-linked immunosorbent assay (ELISA). ZB5-1 also down-regulated the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in a dose-dependent manner by Western blot analysis. Moreover, the effect of ZB5-1 on the nuclear factor-κB (NF-κB) signaling pathway was studied via the expression of phosphorylation of NF-κB p65 and inhibitor of NF-κB (IκB), and the nuclear translocation of NF-κB p65 respectively. The results showed that ZB5-1 could inhibit the phosphorylation of p65 and IκB. Furthermore, molecular docking study suggested that ZB5-1 bound at the active sites of NF-κB to prevent its translocation to the nucleus. Therefore, we suggest ZB5-1 has a potential to reduce the anti-inflammatory response in LPS-induced BV-2 cells. Full article

(This article belongs to the Special Issue Marine Natural Products from Symbiotic Ecosystems)

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12 pages, 2631 KiB

Open AccessArticle

Structural Characterisation of Predicted Helical Regions in the Chironex fleckeri CfTX-1 Toxin

by Athena Andreosso, Paramjit S. Bansal, Michael J. Smout, David Wilson, Jamie E. Seymour and Norelle L. Daly

Mar. Drugs 2018, 16(6), 201; https://doi.org/10.3390/md16060201 - 7 Jun 2018

Cited by 6 | Viewed by 5730

Abstract

The Australian jellyfish Chironex fleckeri, belongs to a family of cubozoan jellyfish known for their potent venoms. CfTX-1 and -2 are two highly abundant toxins in the venom, but there is no structural data available for these proteins. Structural information on toxins [...] Read more.

The Australian jellyfish Chironex fleckeri, belongs to a family of cubozoan jellyfish known for their potent venoms. CfTX-1 and -2 are two highly abundant toxins in the venom, but there is no structural data available for these proteins. Structural information on toxins is integral to the understanding of the mechanism of these toxins and the development of an effective treatment. Two regions of CfTX-1 have been predicted to have helical structures that are involved with the mechanism of action. Here we have synthesized peptides corresponding to these regions and analyzed their structures using NMR spectroscopy. The peptide corresponding to the predicted N-terminal amphiphilic helix appears unstructured in aqueous solution. This lack of structure concurs with structural disorder predicted for this region of the protein using the Protein DisOrder prediction System PrDOS. Conversely, a peptide corresponding to a predicted transmembrane region is very hydrophobic, insoluble in aqueous solution and predicted to be structured by PrDOS. In the presence of SDS-micelles both peptides have well-defined helical structures showing that a membrane mimicking environment stabilizes the structures of both peptides and supports the prediction of the transmembrane region in CfTX-1. This is the first study to experimentally analyze the structure of regions of a C. fleckeri protein. Full article

(This article belongs to the Special Issue Marine Invertebrate Toxins)

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10 pages, 1921 KiB

Open AccessArticle

Tachypleus tridentatus Lectin Enhances Oncolytic Vaccinia Virus Replication to Suppress In Vivo Hepatocellular Carcinoma Growth

by Gongchu Li, Jianhong Cheng, Shengsheng Mei, Tao Wu and Ting Ye

Mar. Drugs 2018, 16(6), 200; https://doi.org/10.3390/md16060200 - 7 Jun 2018

Cited by 16 | Viewed by 3996

Abstract

Lectins play diverse roles in physiological processes as biological recognition molecules. In this report, a gene encoding Tachypleus tridentatus Lectin (TTL) was inserted into an oncolytic vaccinia virus (oncoVV) vector to form oncoVV-TTL, which showed significant antitumor activity in a hepatocellular carcinoma mouse [...] Read more.

Lectins play diverse roles in physiological processes as biological recognition molecules. In this report, a gene encoding Tachypleus tridentatus Lectin (TTL) was inserted into an oncolytic vaccinia virus (oncoVV) vector to form oncoVV-TTL, which showed significant antitumor activity in a hepatocellular carcinoma mouse model. Furthermore, TTL enhanced oncoVV replication through suppressing antiviral factors expression such as interferon-inducible protein 16 (IFI16), mitochondrial antiviral signaling protein (MAVS) and interferon-beta (IFN-β). Further investigations revealed that oncoVV-TTL replication was highly dependent on ERK activity. This study might provide insights into a novel way of the utilization of TTL in oncolytic viral therapies. Full article

(This article belongs to the Special Issue Marine Glycobiology, Glycomics and Lectins)

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9 pages, 955 KiB

Open AccessArticle

Albisporachelin, a New Hydroxamate Type Siderophore from the Deep Ocean Sediment-Derived Actinomycete Amycolatopsis albispora WP1^T

by Qihao Wu, Robert W. Deering, Gaiyun Zhang, Bixia Wang, Xin Li, Jiadong Sun, Jianwei Chen, Huawei Zhang, David C. Rowley and Hong Wang

Mar. Drugs 2018, 16(6), 199; https://doi.org/10.3390/md16060199 - 7 Jun 2018

Cited by 15 | Viewed by 6422

Abstract

Marine actinobacteria continue to be a rich source for the discovery of structurally diverse secondary metabolites. Here we present a new hydroxymate siderophore produced by Amycolatopsis albispora, a recently described species of this less explored actinomycete genus. Strain WP1^T was isolated [...] Read more.

Marine actinobacteria continue to be a rich source for the discovery of structurally diverse secondary metabolites. Here we present a new hydroxymate siderophore produced by Amycolatopsis albispora, a recently described species of this less explored actinomycete genus. Strain WP1^T was isolated from sediments collected at −2945 m in the Indian Ocean. The new siderophore, designated albisporachelin, was isolated from iron depleted culture broths and the structure was established by 1D and 2D NMR and MS/MS experiments, and application of a modified Marfey’s method. Albisporachelin is composed of one N-methylated-formylated/hydroxylated l-ornithine (N-Me-fh-l-Orn), one l-serine (l-Ser), one formylated/hydroxylated l-ornithine (fh-l-Orn) and a cyclo-N-methylated-hydroxylated l-ornithine (cyclo-N-Me-h-l-Orn). Full article

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

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Graphical abstract

16 pages, 8318 KiB

Open AccessFeature PaperArticle

Anti-Obesity Effect of Chitosan Oligosaccharide Capsules (COSCs) in Obese Rats by Ameliorating Leptin Resistance and Adipogenesis

by Haitao Pan, Chuhan Fu, Lanlan Huang, Yao Jiang, Xiaoyi Deng, Jiao Guo and Zhengquan Su

Mar. Drugs 2018, 16(6), 198; https://doi.org/10.3390/md16060198 - 5 Jun 2018

Cited by 62 | Viewed by 7165

Abstract

Obesity is a global disease that causes many metabolic disorders. However, effective agents for the prevention or treatment of obesity remain limited. This study investigated the anti-obesity effect and mechanism of chitosan oligosaccharide capsules (COSCs) on rats suffering from obesity induced by a [...] Read more.

Obesity is a global disease that causes many metabolic disorders. However, effective agents for the prevention or treatment of obesity remain limited. This study investigated the anti-obesity effect and mechanism of chitosan oligosaccharide capsules (COSCs) on rats suffering from obesity induced by a high-fat diet (HFD). After the eight-week administration of COSCs on obese rats, the body weight gain, fat/body ratio, and related biochemical indices were measured. The hepatic expressions of the leptin signal pathway (JAK2-STAT3) and gene expressions of adipogenesis-related targets were also determined. Our data showed that COSCs can regulate body weight gain, lipids, serum alanine aminotransferase, and aspartate aminotransferase, as well as upregulate the hepatic leptin receptor-b (LepRb) and the phosphorylation of JAK2 and STAT3. Meanwhile, marked increased expressions of liver sterol regulatory element-binding protein-1c, fatty acid synthase, acetyl-CoA carboxylase, 3-hydroxy-3-methylglutaryl-CoA reductase, adiponectin, adipose peroxisome proliferator-activated receptor γ, CCAAT-enhancer binding protein α, adipose differentiation-related protein, and SREBP-1c were observed. The results suggested that COSCs activate the JAK2-STAT3 signaling pathway to alleviate leptin resistance and suppress adipogenesis to reduce lipid accumulation. Thus, they can potentially be used for obesity treatment. Full article

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

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15 pages, 819 KiB

Open AccessArticle

Daily Intake of Protein from Cod Residual Material Lowers Serum Concentrations of Nonesterified Fatty Acids in Overweight Healthy Adults: A Randomized Double-Blind Pilot Study

by Iselin Vildmyren, Huy John Vu Cao, Lina Bowitz Haug, Ida Ulrikke Valand, Øyvin Eng, Åge Oterhals, Maren Hoff Austgulen, Alfred Halstensen, Gunnar Mellgren and Oddrun A. Gudbrandsen

Mar. Drugs 2018, 16(6), 197; https://doi.org/10.3390/md16060197 - 5 Jun 2018

Cited by 19 | Viewed by 4469

Abstract

Improved process technologies have allowed fishing vessels to utilize residuals from cod fillet production (head, backbone, skin, cuttings, and entrails) and convert this to high-quality protein powders for human consumption. In this double-blind pilot study, 42 healthy overweight or obese adults were randomized [...] Read more.

Improved process technologies have allowed fishing vessels to utilize residuals from cod fillet production (head, backbone, skin, cuttings, and entrails) and convert this to high-quality protein powders for human consumption. In this double-blind pilot study, 42 healthy overweight or obese adults were randomized to three experimental groups consuming tablets corresponding to 6 g/day of proteins from cod residuals as presscake meal (Cod-PC), presscake and stickwater meal (Cod-PCW), or placebo tablets (control) for eight weeks. The primary outcome of this study was changes in metabolites related to glucose regulation in overweight or obese healthy adults after intake of proteins from cod residuals. Cod-PC supplementation decreased postprandial serum nonesterified fatty acids (NEFA) concentration and increased gene expressions of diglyceride acyltransferase 1 and 2 in subcutaneous adipose tissue compared with controls. Fasting insulin increased while fasting NEFA and 120-min postprandial glucose decreased within the Cod-PC group, but these changes did not differ from the other groups. In conclusion, supplementation with Cod-PC beneficially affected postprandial serum NEFA concentration compared with the other groups in overweight or obese adults. Supplementation with Cod-PCW, which contains a higher fraction of water-soluble protein compared to Cod-PC, did not affect serum markers of glucose regulation. Full article

(This article belongs to the Collection Marine Drugs in the Management of Metabolic Diseases)

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12 pages, 1087 KiB

Open AccessCommunication

Isolation of Marine Bacillus sp. with Antagonistic and Organic-Substances-Degrading Activities and Its Potential Application as a Fish Probiotic

by Shuxin Zhou, Yu Xia, Chongmiao Zhu and Weihua Chu

Mar. Drugs 2018, 16(6), 196; https://doi.org/10.3390/md16060196 - 5 Jun 2018

Cited by 33 | Viewed by 6070

Abstract

We report on the isolation and characterization of an acid- and bile-tolerant bacterial strain, Bacillus sp. YB1701 with antibacterial and quorum-quenching activity. Strain YB1701 was isolated from coastal sediment samples and characterized by biochemical tests and 16S rRNA sequencing. In vitro study indicated [...] Read more.

We report on the isolation and characterization of an acid- and bile-tolerant bacterial strain, Bacillus sp. YB1701 with antibacterial and quorum-quenching activity. Strain YB1701 was isolated from coastal sediment samples and characterized by biochemical tests and 16S rRNA sequencing. In vitro study indicated that strain YB1701 can survive at pH 2.0 for up to 3 h and tolerate bile up to 2.0% concentration even after 12 h of exposure. Strain YB1701 showed antimicrobial activity against fish pathogens Aeromonas hydrophila and Vibrio parahemolyticus using an agar well diffusion assay. The trial test showed dietary supplementation of YB1701 significantly improved the resistance of Carassius auratus gibelio against A. hydrophila challenge. The safety assessment revealed that the isolate Bacillus sp. YB1701 was not cytotoxic to Carassius auratus gibelio or mice and did not exhibit hemolytic activity on rabbit blood agar plate. Disc-diffusion assays using a panel of antibiotics listed by the European Food Safety Authority (EFSA) showed that YB1701 was susceptible to selected antibiotics. Under laboratory conditions, the degradation rate of organic waste (predominately fish excrement) for 14 days by YB1701 was 79.69%. Results from the present study suggest that strain YB1701 is a potential probiotic strain and can be used in aquaculture for degrading organic waste and improving disease resistance of fish against bacterial infection. Further study is needed to assess the utility of strain YB1701 on a commercial scale. Full article

(This article belongs to the Special Issue Marine Probiotics and Prebiotics: Characterization and Prospects for the Development of New Drugs/Nutraceuticals)

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14 pages, 1722 KiB

Open AccessArticle

Effect of Tetrodotoxin Pellets in a Rat Model of Postherpetic Neuralgia

by Bihong Hong, Jipeng Sun, Hongzhi Zheng, Qingqing Le, Changsen Wang, Kaikai Bai, Jianlin He, Huanghuang He and Yanming Dong

Mar. Drugs 2018, 16(6), 195; https://doi.org/10.3390/md16060195 - 5 Jun 2018

Cited by 25 | Viewed by 5143

Abstract

Postherpetic neuralgia (PHN) is nerve pain caused by a reactivation of the varicella zoster virus. Medications are used to reduce PHN but their use is limited by serious side effects. Tetrodotoxin (TTX) is a latent neurotoxin that can block neuropathic pain, but its [...] Read more.

Postherpetic neuralgia (PHN) is nerve pain caused by a reactivation of the varicella zoster virus. Medications are used to reduce PHN but their use is limited by serious side effects. Tetrodotoxin (TTX) is a latent neurotoxin that can block neuropathic pain, but its therapeutic index is only 3–5 times with intravenous or intramuscular injection. Therefore, we prepared oral TTX pellets and examined their effect in a rat model of PHN induced by resiniferatoxin (RTX). Oral TTX pellets were significantly effective at preventing RTX-induced mechanical and thermal allodynia, and similar to pregabalin. Moreover, oral administration of TTX pellets dose-dependently inhibited RTX-induced PHN compared with intramuscular administration of TTX injection. We also studied the pharmacokinetic profile of TTX pellets. Our results showed that the blood concentration of TTX reached a maximum plasma concentration (C_max) at around 2 h, with an elimination half-life time (t_1/2) of 3.23 ± 1.74 h after intragastric administration. The median lethal dose (LD₅₀) of TTX pellets was 517.43 μg/kg via oral administration to rats, while the median effective dose (ED50) was approximately 5.85 μg/kg, and the therapeutic index was 88.45. Altogether, this has indicated that oral TTX pellets greatly enhance safety when compared with TTX injection. Full article

(This article belongs to the Special Issue Pre-Clinical Marine Drug Discovery)

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36 pages, 16637 KiB

Open AccessReview

Novel Natural Products from Extremophilic Fungi

by Xuan Zhang, Shou-Jie Li, Jin-Jie Li, Zi-Zhen Liang and Chang-Qi Zhao

Mar. Drugs 2018, 16(6), 194; https://doi.org/10.3390/md16060194 - 4 Jun 2018

Cited by 56 | Viewed by 7762

Abstract

Extremophilic fungi have been found to develop unique defences to survive extremes of pressure, temperature, salinity, desiccation, and pH, leading to the biosynthesis of novel natural products with diverse biological activities. The present review focuses on new extremophilic fungal natural products published from [...] Read more.

Extremophilic fungi have been found to develop unique defences to survive extremes of pressure, temperature, salinity, desiccation, and pH, leading to the biosynthesis of novel natural products with diverse biological activities. The present review focuses on new extremophilic fungal natural products published from 2005 to 2017, highlighting the chemical structures and their biological potential. Full article

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

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14 pages, 2151 KiB

Open AccessFeature PaperArticle

Commercial Fucoidans from Fucus vesiculosus Can Be Grouped into Antiadipogenic and Adipogenic Agents

by Ruth Medeiros Oliveira, Rafael Barros Gomes Câmara, Jessyka Fernanda Santiago Monte, Rony Lucas Silva Viana, Karoline Rachel Teodosio Melo, Moacir Fernandes Queiroz, Luciana Guimarães Alves Filgueira, Lila Missae Oyama and Hugo Alexandre Oliveira Rocha

Mar. Drugs 2018, 16(6), 193; https://doi.org/10.3390/md16060193 - 4 Jun 2018

Cited by 21 | Viewed by 4798

Abstract

Fucus vesiculosus is a brown seaweed used in the treatment of obesity. This seaweed synthesizes various bioactive molecules, one of them being a sulfated polysaccharide known as fucoidan (FF). This polymer can easily be found commercially, and has antiadipogenic and lipolytic activity. Using [...] Read more.

Fucus vesiculosus is a brown seaweed used in the treatment of obesity. This seaweed synthesizes various bioactive molecules, one of them being a sulfated polysaccharide known as fucoidan (FF). This polymer can easily be found commercially, and has antiadipogenic and lipolytic activity. Using differential precipitation with acetone, we obtained four fucoidan-rich fractions (F0.5/F0.9/F1.1/F2.0) from FF. These fractions contain different proportions of fucose:glucuronic acid:galactose:xylose:sulfate, and also showed different electrophoretic mobility and antioxidant activity. Using 3T3-L1 adipocytes, we found that all samples had lipolytic action, especially F2.0, which tripled the amount of glycerol in the cellular medium. Moreover, we observed that FF, F1.0, and F2.0 have antiadipogenic activity, as they inhibited the oil red staining by cells at 40%, 40%, and 50%, respectively. In addition, they decreased the expression of key proteins of adipogenic differentiation (C/EBPα, C/EBPβ, and PPARγ). However, F0.5 and F0.9 stimulated the oil red staining at 80% and increased the expression of these proteins. Therefore, these fucoidan fractions have an adipogenic effect. Overall, the data show that F2.0 has great potential to be used as an agent against obesity as it displays better antioxidant, lipolytic and antiadipogenic activities than the other fucoidan fractions that we tested. Full article

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

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14 pages, 3454 KiB

Open AccessCommunication

A Novel Atypical PKC-Iota Inhibitor, Echinochrome A, Enhances Cardiomyocyte Differentiation from Mouse Embryonic Stem Cells

by Hyoung Kyu Kim, Sung Woo Cho, Hye Jin Heo, Seung Hun Jeong, Min Kim, Kyung Soo Ko, Byoung Doo Rhee, Natalia P. Mishchenko, Elena A. Vasileva, Sergey A. Fedoreyev, Valentin A. Stonik and Jin Han

Mar. Drugs 2018, 16(6), 192; https://doi.org/10.3390/md16060192 - 2 Jun 2018

Cited by 17 | Viewed by 5733

Abstract

Echinochrome A (EchA) is a marine bioproduct extracted from sea urchins having antioxidant, antimicrobial, anti-inflammatory, and chelating effects, and is the active component of the clinical drug histochrome. We investigated the potential use of Ech A for inducing cardiomyocyte differentiation from mouse embryonic [...] Read more.

Echinochrome A (EchA) is a marine bioproduct extracted from sea urchins having antioxidant, antimicrobial, anti-inflammatory, and chelating effects, and is the active component of the clinical drug histochrome. We investigated the potential use of Ech A for inducing cardiomyocyte differentiation from mouse embryonic stem cells (mESCs). We also assessed the effects of Ech A on mitochondrial mass, inner membrane potential (Δψm), reactive oxygen species generation, and levels of Ca²⁺. To identify the direct target of Ech A, we performed in vitro kinase activity and surface plasmon resonance binding assays. Ech A dose-dependently enhanced cardiomyocyte differentiation with higher beating rates. Ech A (50 μM) increased the mitochondrial mass and membrane potential but did not alter the mitochondrial superoxide and Ca²⁺ levels. The in vitro kinase activity of the atypical protein kinase C-iota (PKCι) was significantly decreased by 50 μM of Ech A with an IC₅₀ for PKCι activity of 107 μM. Computational protein-ligand docking simulation results suggested the direct binding of Ech A to PKCι, and surface plasmon resonance confirmed the direct binding with a low K_D of 6.3 nM. Therefore, Ech A is a potential drug for enhancing cardiomyocyte differentiation from mESCs through direct binding to PKCι and inhibition of its activity. Full article

(This article belongs to the Special Issue Marine Drugs Interact with Functional Proteins)

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8 pages, 1625 KiB

Open AccessArticle

Heterologous Expression of a VioA Variant Activates Cryptic Compounds in a Marine-Derived Brevibacterium Strain

by Xiao Han, Lukuan Hou, Jing Hou, Yongyu Zhang, Huayue Li and Wenli Li

Mar. Drugs 2018, 16(6), 191; https://doi.org/10.3390/md16060191 - 2 Jun 2018

Cited by 3 | Viewed by 4227

Abstract

A new 14-membered homodimeric macrodiolide, brevidiolide (3), along with four known aromatic compounds (1, 2, 4 and 5) were obtained by heterologous expression of the recombinant plasmid pWLI823 expressing the G231L variant of VioA in the marine-derived [...] Read more.

A new 14-membered homodimeric macrodiolide, brevidiolide (3), along with four known aromatic compounds (1, 2, 4 and 5) were obtained by heterologous expression of the recombinant plasmid pWLI823 expressing the G231L variant of VioA in the marine-derived Brevibacterium sp. 7002-073. The structures of 1–5 were elucidated on the basis of LC-MS and 2D NMR spectroscopic analyses. In the evaluation for the antibacterial activities of the compounds against multi-drug resistant (MDR) strains, 5 showed notable growth inhibition against Staphylococcus aureus CCARM 3090 and Klebsiella pneumoniae ATCC 13883, with a minimum inhibitory concentration (MIC) value of 3.12 µg/mL. Full article

(This article belongs to the Special Issue Microbial Gene Clusters of Marine Origin)

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13 pages, 1477 KiB

Open AccessArticle

Optimum Production Conditions, Purification, Identification, and Antioxidant Activity of Violaxanthin from Microalga Eustigmatos cf. polyphem (Eustigmatophyceae)

by Feifei Wang, Luodong Huang, Baoyan Gao and Chengwu Zhang

Mar. Drugs 2018, 16(6), 190; https://doi.org/10.3390/md16060190 - 1 Jun 2018

Cited by 42 | Viewed by 5731

Abstract

Violaxanthin is a major xanthophyll pigment in the microalga Eustigmatos cf. polyphem, but the amount produced after propagation can vary depending upon culture conditions. In this study, the effects of cultivation time, nitrogen concentration, light intensity, and culture mode on violaxanthin production [...] Read more.

Violaxanthin is a major xanthophyll pigment in the microalga Eustigmatos cf. polyphem, but the amount produced after propagation can vary depending upon culture conditions. In this study, the effects of cultivation time, nitrogen concentration, light intensity, and culture mode on violaxanthin production were investigated. The results showed that this microalga vigorously grew and maintained a high level of violaxanthin in the fed-batch culture, and the highest violaxanthin productivity of 1.10 ± 0.03 mg L⁻¹ d⁻¹ was obtained under low light illumination with 18 mM of initial nitrogen supply for ten days. Additionally, violaxanthin was purified from E. cf. polyphem by silica gel chromatography and preparative high-performance liquid chromatography (PHPLC), and identified with high-resolution mass spectrometry (HRMS). The antioxidant activity of the purified violaxanthin was evaluated by three tests in vitro: reducing power assay, 2,2-diphenyl-1-picrylhydrazyl (DPPH), and 2,2-azobis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) radical assays. The strongest inhibition of purified violaxanthin occurred during the scavenging of ABTS⁺ radicals, with EC₅₀ of 15.25 μg mL⁻¹. In conclusion, this is the first report to investigate the effects of different culture conditions on violaxanthin accumulation in E. cf. polyphem and provide a novel source for the production of violaxanthin that can be used for food and pharmaceutical applications. Full article

(This article belongs to the Special Issue Advances in Marine Natural Product Characterisation and Separation Methodologies)

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11 pages, 1677 KiB

Open AccessArticle

HSQC-TOCSY Fingerprinting-Directed Discovery of Antiplasmodial Polyketides from the Marine Ascidian-Derived Streptomyces sp. (USC-16018)

by Larissa Buedenbender, Luke P. Robertson, Leonardo Lucantoni, Vicky M. Avery, D. İpek Kurtböke and Anthony R. Carroll

Mar. Drugs 2018, 16(6), 189; https://doi.org/10.3390/md16060189 - 30 May 2018

Cited by 18 | Viewed by 5190

Abstract

Chemical investigations on the fermentation extract obtained from an ascidian-derived Streptomyces sp. (USC-16018) yielded a new ansamycin polyketide, herbimycin G (1), as well as a known macrocyclic polyketide, elaiophylin (2), and four known diketopiperazines (3–6). [...] Read more.

Chemical investigations on the fermentation extract obtained from an ascidian-derived Streptomyces sp. (USC-16018) yielded a new ansamycin polyketide, herbimycin G (1), as well as a known macrocyclic polyketide, elaiophylin (2), and four known diketopiperazines (3–6). The structures of the compounds were elucidated based on 1D/2D NMR and MS data. The absolute configuration of 1 was established by comparison of experimental and predicted electronic circular dichroism (ECD) data. Antiplasmodial activities were tested for the natural products against chloroquine sensitive (3D7) and chloroquine resistant (Dd2) Plasmodium falciparum strains; the two polyketides (1–2) demonstrated an inhibition of >75% against both parasite strains and while 2 was highly cytotoxic, herbimycin G (1) showed no cytotoxicity and good predicted water solubility. Full article

(This article belongs to the Special Issue Marine Natural Products from Symbiotic Ecosystems)

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26 pages, 362 KiB

Open AccessReview

Phycotoxins in Marine Shellfish: Origin, Occurrence and Effects on Humans

by Federica Farabegoli, Lucía Blanco, Laura P. Rodríguez, Juan Manuel Vieites and Ana García Cabado

Mar. Drugs 2018, 16(6), 188; https://doi.org/10.3390/md16060188 - 29 May 2018

Cited by 128 | Viewed by 10776

Abstract

Massive phytoplankton proliferation, and the consequent release of toxic metabolites, can be responsible for seafood poisoning outbreaks: filter-feeding mollusks, such as shellfish, mussels, oysters or clams, can accumulate these toxins throughout the food chain and present a threat for consumers’ health. Particular environmental [...] Read more.

Massive phytoplankton proliferation, and the consequent release of toxic metabolites, can be responsible for seafood poisoning outbreaks: filter-feeding mollusks, such as shellfish, mussels, oysters or clams, can accumulate these toxins throughout the food chain and present a threat for consumers’ health. Particular environmental and climatic conditions favor this natural phenomenon, called harmful algal blooms (HABs); the phytoplankton species mostly involved in these toxic events are dinoflagellates or diatoms belonging to the genera Alexandrium, Gymnodinium, Dinophysis, and Pseudo-nitzschia. Substantial economic losses ensue after HABs occurrence: the sectors mainly affected include commercial fisheries, tourism, recreational activities, and public health monitoring and management. A wide range of symptoms, from digestive to nervous, are associated to human intoxication by biotoxins, characterizing different and specific syndromes, called paralytic shellfish poisoning, amnesic shellfish poisoning, diarrhetic shellfish poisoning, and neurotoxic shellfish poisoning. This review provides a complete and updated survey of phycotoxins usually found in marine invertebrate organisms and their relevant properties, gathering information about the origin, the species where they were found, as well as their mechanism of action and main effects on humans. Full article

(This article belongs to the Special Issue Marine Invertebrate Toxins)

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Mar. Drugs, Volume 16, Issue 6 (June 2018) – 42 articles

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