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Mar. Drugs, Volume 14, Issue 1 (January 2016) – 24 articles

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239 KiB  
Editorial
Acknowledgement to Reviewers of Marine Drugs in 2015
by Marine Drugs Editorial Office
Mar. Drugs 2016, 14(1), 25; https://doi.org/10.3390/md14010025 - 21 Jan 2016
Viewed by 4383
Abstract
The editors of Marine Drugs would like to express their sincere gratitude to the following reviewers for assessing manuscripts in 2015. [...] Full article
1229 KiB  
Article
Liquid Chromatography-Mass Spectrometry-Based Rapid Secondary-Metabolite Profiling of Marine Pseudoalteromonas sp. M2
by Woo Jung Kim, Young Ok Kim, Jin Hee Kim, Bo-Hye Nam, Dong-Gyun Kim, Cheul Min An, Jun Sik Lee, Pan Soo Kim, Hye Min Lee, Joa-Sup Oh and Jong Suk Lee
Mar. Drugs 2016, 14(1), 24; https://doi.org/10.3390/md14010024 - 20 Jan 2016
Cited by 29 | Viewed by 6339
Abstract
The ocean is a rich resource of flora, fauna, and food. A wild-type bacterial strain showing confluent growth on marine agar with antibacterial activity was isolated from marine water, identified using 16S rDNA sequence analysis as Pseudoalteromonas sp., and designated as strain M2. [...] Read more.
The ocean is a rich resource of flora, fauna, and food. A wild-type bacterial strain showing confluent growth on marine agar with antibacterial activity was isolated from marine water, identified using 16S rDNA sequence analysis as Pseudoalteromonas sp., and designated as strain M2. This strain was found to produce various secondary metabolites including quinolone alkaloids. Using high-resolution mass spectrometry (MS) and nuclear magnetic resonance (NMR) analysis, we identified nine secondary metabolites of 4-hydroxy-2-alkylquinoline (pseudane-III, IV, V, VI, VII, VIII, IX, X, and XI). Additionally, this strain produced two novel, closely related compounds, 2-isopentylqunoline-4-one and 2-(2,3-dimetylbutyl)qunoline-4-(1H)-one, which have not been previously reported from marine bacteria. From the metabolites produced by Pseudoalteromonas sp. M2, 2-(2,3-dimethylbutyl)quinolin-4-one, pseudane-VI, and pseudane-VII inhibited melanin synthesis in Melan-A cells by 23.0%, 28.2%, and 42.7%, respectively, wherein pseudane-VII showed the highest inhibition at 8 µg/mL. The results of this study suggest that liquid chromatography (LC)-MS/MS-based metabolite screening effectively improves the efficiency of novel metabolite discovery. Additionally, these compounds are promising candidates for further bioactivity development. Full article
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4493 KiB  
Review
Biologically Active Oxylipins from Enzymatic and Nonenzymatic Routes in Macroalgae
by Mariana Barbosa, Patrícia Valentão and Paula B. Andrade
Mar. Drugs 2016, 14(1), 23; https://doi.org/10.3390/md14010023 - 20 Jan 2016
Cited by 56 | Viewed by 7648
Abstract
Marine algae are rich and heterogeneous sources of great chemical diversity, among which oxylipins are a well-recognized class of natural products. Algal oxylipins comprise an assortment of oxygenated, halogenated, and unsaturated functional groups and also several carbocycles, varying in ring size and position [...] Read more.
Marine algae are rich and heterogeneous sources of great chemical diversity, among which oxylipins are a well-recognized class of natural products. Algal oxylipins comprise an assortment of oxygenated, halogenated, and unsaturated functional groups and also several carbocycles, varying in ring size and position in lipid chain. Besides the discovery of structurally diverse oxylipins in macroalgae, research has recently deciphered the role of some of these metabolites in the defense and innate immunity of photosynthetic marine organisms. This review is an attempt to comprehensively cover the available literature on the chemistry, biosynthesis, ecology, and potential bioactivity of oxylipins from marine macroalgae. For a better understanding, enzymatic and nonenzymatic routes were separated; however, both processes often occur concomitantly and may influence each other, even producing structurally related molecules. Full article
(This article belongs to the Special Issue Marine Fatty Acids-2016)
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Article
Stomach Chitinase from Japanese Sardine Sardinops melanostictus: Purification, Characterization, and Molecular Cloning of Chitinase Isozymes with a Long Linker
by Satoshi Kawashima, Hiroki Ikehata, Chihiro Tada, Tomohiro Ogino, Hiromi Kakizaki, Mana Ikeda, Hideto Fukushima and Masahiro Matsumiya
Mar. Drugs 2016, 14(1), 22; https://doi.org/10.3390/md14010022 - 20 Jan 2016
Cited by 14 | Viewed by 6771
Abstract
Fish express two different chitinases, acidic fish chitinase-1 (AFCase-1) and acidic fish chitinase-2 (AFCase-2), in the stomach. AFCase-1 and AFCase-2 have different degradation patterns, as fish efficiently degrade chitin ingested as food. For a comparison with the enzymatic properties and the primary structures [...] Read more.
Fish express two different chitinases, acidic fish chitinase-1 (AFCase-1) and acidic fish chitinase-2 (AFCase-2), in the stomach. AFCase-1 and AFCase-2 have different degradation patterns, as fish efficiently degrade chitin ingested as food. For a comparison with the enzymatic properties and the primary structures of chitinase isozymes obtained previously from the stomach of demersal fish, in this study, we purified chitinase isozymes from the stomach of Japanese sardine Sardinops melanostictus, a surface fish that feeds on plankton, characterized the properties of these isozymes, and cloned the cDNAs encoding chitinases. We also predicted 3D structure models using the primary structures of S. melanostictus stomach chitinases. Two chitinase isozymes, SmeChiA (45 kDa) and SmeChiB (56 kDa), were purified from the stomach of S. melanostictus. Moreover, two cDNAs, SmeChi-1 encoding SmeChiA, and SmeChi-2 encoding SmeChiB were cloned. The linker regions of the deduced amino acid sequences of SmeChi-1 and SmeChi-2 (SmeChi-1 and SmeChi-2) are the longest among the fish stomach chitinases. In the cleavage pattern groups toward short substrates and the phylogenetic tree analysis, SmeChi-1 and SmeChi-2 were classified into AFCase-1 and AFCase-2, respectively. SmeChi-1 and SmeChi-2 had catalytic domains that consisted of a TIM-barrel (β/α)8–fold structure and a deep substrate-binding cleft. This is the first study showing the 3D structure models of fish stomach chitinases. Full article
(This article belongs to the Special Issue Green Chemistry Approach to Marine Products)
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Article
Effects of Halide Ions on the Carbamidocyclophane Biosynthesis in Nostoc sp. CAVN2
by Michael Preisitsch, Stefan E. Heiden, Monika Beerbaum, Timo H. J. Niedermeyer, Marie Schneefeld, Jennifer Herrmann, Jana Kumpfmüller, Andrea Thürmer, Inga Neidhardt, Christoph Wiesner, Rolf Daniel, Rolf Müller, Franz-Christoph Bange, Peter Schmieder, Thomas Schweder and Sabine Mundt
Mar. Drugs 2016, 14(1), 21; https://doi.org/10.3390/md14010021 - 20 Jan 2016
Cited by 33 | Viewed by 10840
Abstract
In this study, the influence of halide ions on [7.7]paracyclophane biosynthesis in the cyanobacterium Nostoc sp. CAVN2 was investigated. In contrast to KI and KF, supplementation of the culture medium with KCl or KBr resulted not only in an increase of growth but [...] Read more.
In this study, the influence of halide ions on [7.7]paracyclophane biosynthesis in the cyanobacterium Nostoc sp. CAVN2 was investigated. In contrast to KI and KF, supplementation of the culture medium with KCl or KBr resulted not only in an increase of growth but also in an up-regulation of carbamidocyclophane production. LC-MS analysis indicated the presence of chlorinated, brominated, but also non-halogenated derivatives. In addition to 22 known cylindrocyclophanes and carbamidocyclophanes, 27 putative congeners have been detected. Nine compounds, carbamidocyclophanes M−U, were isolated, and their structural elucidation by 1D and 2D NMR experiments in combination with HRMS and ECD analysis revealed that they are brominated analogues of chlorinated carbamidocyclophanes. Quantification of the carbamidocyclophanes showed that chloride is the preferably utilized halide, but incorporation is reduced in the presence of bromide. Evaluation of the antibacterial activity of 30 [7.7]paracyclophanes and related derivatives against selected pathogenic Gram-positive and Gram-negative bacteria exhibited remarkable effects especially against methicillin- and vancomycin-resistant staphylococci and Mycobacterium tuberculosis. For deeper insights into the mechanisms of biosynthesis, the carbamidocyclophane biosynthetic gene cluster in Nostoc sp. CAVN2 was studied. The gene putatively coding for the carbamoyltransferase has been identified. Based on bioinformatic analyses, a possible biosynthetic assembly is discussed. Full article
(This article belongs to the Special Issue Compounds from Cyanobacteria)
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1895 KiB  
Review
Natural Products from Marine Fungi—Still an Underrepresented Resource
by Johannes F. Imhoff
Mar. Drugs 2016, 14(1), 19; https://doi.org/10.3390/md14010019 - 16 Jan 2016
Cited by 183 | Viewed by 13770
Abstract
Marine fungi represent a huge potential for new natural products and an increased number of new metabolites have become known over the past years, while much of the hidden potential still needs to be uncovered. Representative examples of biodiversity studies of marine fungi [...] Read more.
Marine fungi represent a huge potential for new natural products and an increased number of new metabolites have become known over the past years, while much of the hidden potential still needs to be uncovered. Representative examples of biodiversity studies of marine fungi and of natural products from a diverse selection of marine fungi from the author’s lab are highlighting important aspects of this research. If one considers the huge phylogenetic diversity of marine fungi and their almost ubiquitous distribution, and realizes that most of the published work on secondary metabolites of marine fungi has focused on just a few genera, strictly speaking Penicillium, Aspergillus and maybe also Fusarium and Cladosporium, the diversity of marine fungi is not adequately represented in investigations on their secondary metabolites and the less studied species deserve special attention. In addition to results on recently discovered new secondary metabolites of Penicillium species, the diversity of fungi in selected marine habitats is highlighted and examples of groups of secondary metabolites produced by representatives of a variety of different genera and their bioactivities are presented. Special focus is given to the production of groups of derivatives of metabolites by the fungi and to significant differences in biological activities due to small structural changes. Full article
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Review
Marine Isonitriles and Their Related Compounds
by Jens Emsermann, Ulrich Kauhl and Till Opatz
Mar. Drugs 2016, 14(1), 16; https://doi.org/10.3390/md14010016 - 14 Jan 2016
Cited by 59 | Viewed by 9403
Abstract
Marine isonitriles represent the largest group of natural products carrying the remarkable isocyanide moiety. Together with marine isothiocyanates and formamides, which originate from the same biosynthetic pathways, they offer diverse biological activities and in spite of their exotic nature they may constitute potential [...] Read more.
Marine isonitriles represent the largest group of natural products carrying the remarkable isocyanide moiety. Together with marine isothiocyanates and formamides, which originate from the same biosynthetic pathways, they offer diverse biological activities and in spite of their exotic nature they may constitute potential lead structures for pharmaceutical development. Among other biological activities, several marine isonitriles show antimalarial, antitubercular, antifouling and antiplasmodial effects. In contrast to terrestrial isonitriles, which are mostly derived from α-amino acids, the vast majority of marine representatives are of terpenoid origin. An overview of all known marine isonitriles and their congeners will be given and their biological and chemical aspects will be discussed. Full article
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Article
Five New Cytotoxic Metabolites from the Marine Fungus Neosartorya pseudofischeri
by Wen-Jian Lan, Sheng-Jiao Fu, Meng-Yang Xu, Wan-Ling Liang, Chi-Keung Lam, Guo-Hua Zhong, Jun Xu, De-Po Yang and Hou-Jin Li
Mar. Drugs 2016, 14(1), 18; https://doi.org/10.3390/md14010018 - 13 Jan 2016
Cited by 34 | Viewed by 5961
Abstract
The marine fungus Neosartorya pseudofischeri was isolated from Acanthaster planci from the South China Sea. In a preliminary bioactivity screening, the crude methanol extract of the fungal mycelia showed significant inhibitory activity against the Sf9 cell line from the fall armyworm Spodoptera frugiperda [...] Read more.
The marine fungus Neosartorya pseudofischeri was isolated from Acanthaster planci from the South China Sea. In a preliminary bioactivity screening, the crude methanol extract of the fungal mycelia showed significant inhibitory activity against the Sf9 cell line from the fall armyworm Spodoptera frugiperda. Five novel compounds, including 5-olefin phenylpyropene A (1), 13-dehydroxylpyripyropene A (4), deacetylsesquiterpene (7), 5-formyl-6-hydroxy-8-isopropyl-2- naphthoic acid (9) and 6,8-dihydroxy-3-((1E,3E)-penta-1,3-dien-1-yl)isochroman-1-one (10), together with eleven known compounds, phenylpyropene A (2) and C (3), pyripyropene A (5), 7-deacetylpyripyropene A (6), (1S,2R,4aR,5R,8R,8aR)-1,8a-dihydroxy-2-acetoxy-3,8-dimethyl-5- (prop-1-en-2-yl)-1,2,4a, 5,6,7,8,8a-octahydronaphthalene (8), isochaetominine C (11), trichodermamide A (12), indolyl-3-acetic acid methyl ester (13), 1-acetyl-β-carboline (14), 1,2,3,4-tetrahydro-6-hydroxyl-2-methyl-l,3,4-trioxopyrazino[l,2-a]-indole (15) and fumiquinazoline F (16), were obtained. The structures of these compounds were determined mainly by MS and NMR data. The absolute configuration of 9 was assigned by the single-crystal X-ray diffraction studies. Compounds 111 and 15 showed significant cytotoxicity against the Sf9 cells from S. frugiperda. Full article
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16806 KiB  
Review
Cyanobacterial Metabolite Calothrixins: Recent Advances in Synthesis and Biological Evaluation
by Su Xu, Bhavitavya Nijampatnam, Shilpa Dutta and Sadanandan E. Velu
Mar. Drugs 2016, 14(1), 17; https://doi.org/10.3390/md14010017 - 12 Jan 2016
Cited by 41 | Viewed by 8876
Abstract
The marine environment is host to unparalleled biological and chemical diversity, making it an attractive resource for the discovery of new therapeutics for a plethora of diseases. Compounds that are extracted from cyanobacteria are of special interest due to their unique structural scaffolds [...] Read more.
The marine environment is host to unparalleled biological and chemical diversity, making it an attractive resource for the discovery of new therapeutics for a plethora of diseases. Compounds that are extracted from cyanobacteria are of special interest due to their unique structural scaffolds and capacity to produce potent pharmaceutical and biotechnological traits. Calothrixins A and B are two cyanobacterial metabolites with a structural assembly of quinoline, quinone, and indole pharmacophores. This review surveys recent advances in the synthesis and evaluation of the biological activities of calothrixins. Due to the low isolation yields from the marine source and the promise this scaffold holds for anticancer and antimicrobial drugs, organic and medicinal chemists around the world have embarked on developing efficient synthetic routes to produce calothrixins. Since the first review appeared in 2009, 11 novel syntheses of calothrixins have been published in the efforts to develop methods that contain fewer steps and higher-yielding reactions. Calothrixins have shown their potential as topoisomerase I poisons for their cytotoxicity in cancer. They have also been observed to target various aspects of RNA synthesis in bacteria. Further investigation into the exact mechanism for their bioactivity is still required for many of its analogs. Full article
(This article belongs to the Special Issue Compounds from Cyanobacteria)
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3096 KiB  
Article
The Oligo Fucoidan Inhibits Platelet-Derived Growth Factor-Stimulated Proliferation of Airway Smooth Muscle Cells
by Chao-Huei Yang, Chiung-Fang Tsao, Wang-Sheng Ko and Ya-Ling Chiou
Mar. Drugs 2016, 14(1), 15; https://doi.org/10.3390/md14010015 - 09 Jan 2016
Cited by 13 | Viewed by 5976
Abstract
In the pathogenesis of asthma, the proliferation of airway smooth muscle cells (ASMCs) is a key factor in airway remodeling and causes airway narrowing. In addition, ASMCs are also the effector cells of airway inflammation. Fucoidan extracted from marine brown algae polysaccharides has [...] Read more.
In the pathogenesis of asthma, the proliferation of airway smooth muscle cells (ASMCs) is a key factor in airway remodeling and causes airway narrowing. In addition, ASMCs are also the effector cells of airway inflammation. Fucoidan extracted from marine brown algae polysaccharides has antiviral, antioxidant, antimicrobial, anticlotting, and anticancer properties; however, its effectiveness for asthma has not been elucidated thus far. Platelet-derived growth factor (PDGF)-treated primary ASMCs were cultured with or without oligo-fucoidan (100, 500, or 1000 µg/mL) to evaluate its effects on cell proliferation, cell cycle, apoptosis, and Akt, ERK1/2 signaling pathway. We found that PDGF (40 ng/mL) increased the proliferation of ASMCs by 2.5-fold after 48 h (p < 0.05). Oligo-fucoidan reduced the proliferation of PDGF-stimulated ASMCs by 75%–99% after 48 h (p < 0.05) and induced G1/G0 cell cycle arrest, but did not induce apoptosis. Further, oligo-fucoidan supplementation reduced PDGF-stimulated extracellular signal-regulated kinase (ERK1/2), Akt, and nuclear factor (NF)-κB phosphorylation. Taken together, oligo-fucoidan supplementation might reduce proliferation of PDGF-treated ASMCs through the suppression of ERK1/2 and Akt phosphorylation and NF-κB activation. The results provide basis for future animal experiments and human trials. Full article
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Article
Anti-Inflammatory Activity of Tanzawaic Acid Derivatives from a Marine-Derived Fungus Penicillium steckii 108YD142
by Hee Jae Shin, Gam Bang Pil, Soo-Jin Heo, Hyi-Seung Lee, Jong Seok Lee, Yeon-Ju Lee, Jihoon Lee and Ho Shik Won
Mar. Drugs 2016, 14(1), 14; https://doi.org/10.3390/md14010014 - 08 Jan 2016
Cited by 34 | Viewed by 6616
Abstract
Chemical investigation of a marine-derived fungus, Penicillium steckii 108YD142, resulted in the discovery of a new tanzawaic acid derivative, tanzawaic acid Q (1), together with four known analogues, tanzawaic acids A (2), C (3), D (4 [...] Read more.
Chemical investigation of a marine-derived fungus, Penicillium steckii 108YD142, resulted in the discovery of a new tanzawaic acid derivative, tanzawaic acid Q (1), together with four known analogues, tanzawaic acids A (2), C (3), D (4), and K (5). The structures of tanzawaic acid derivatives 15 were determined by the detailed analysis of 1D, 2D NMR and LC-MS data, along with chemical methods and literature data analysis. These compounds significantly inhibited nitric oxide (NO) production and the new tanzawaic acid Q (1) inhibited the lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins and mRNA expressions in RAW 264.7 macrophages. Additionally, compound 1 reduced the mRNA levels of inflammatory cytokines. Taken together, the results of this study demonstrated that the new tanzawaic acid derivative inhibits LPS-induced inflammation. This is the first report on the anti-inflammatory activity of tanzawaic acid Q (1). Full article
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Article
Inhibition of Ultraviolet B-Induced Expression of the Proinflammatory Cytokines TNF-α and VEGF in the Cornea by Fucoxanthin Treatment in a Rat Model
by Shiu-Jau Chen, Ching-Ju Lee, Tzer-Bin Lin, Hsiang-Jui Liu, Shuan-Yu Huang, Jia-Zeng Chen and Kuang-Wen Tseng
Mar. Drugs 2016, 14(1), 13; https://doi.org/10.3390/md14010013 - 07 Jan 2016
Cited by 29 | Viewed by 5088
Abstract
Ultraviolet B (UVB) irradiation is the most common cause of radiation damage to the eyeball and is a risk factor for human corneal damage. We determined the protective effect of fucoxanthin, which is a carotenoid found in common edible seaweed, on ocular tissues [...] Read more.
Ultraviolet B (UVB) irradiation is the most common cause of radiation damage to the eyeball and is a risk factor for human corneal damage. We determined the protective effect of fucoxanthin, which is a carotenoid found in common edible seaweed, on ocular tissues against oxidative UVB-induced corneal injury. The experimental rats were intravenously injected with fucoxanthin at doses of 0.5, 5 mg/kg body weight/day or with a vehicle before UVB irradiation. Lissamine green for corneal surface staining showed that UVB irradiation caused serious damage on the corneal surface, including severe epithelial exfoliation and deteriorated epithelial smoothness. Histopathological lesion examination revealed that levels of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α) and vascular endothelial growth factor (VEGF), significantly increased. However, pretreatment with fucoxanthin inhibited UVB radiation-induced corneal disorders including evident preservation of corneal surface smoothness, downregulation of proinflammatory cytokine expression, and decrease of infiltrated polymorphonuclear leukocytes from UVB-induced damage. Moreover, significant preservation of the epithelial integrity and inhibition of stromal swelling were also observed after UVB irradiation in fucoxanthin-treated groups. Pretreatment with fucoxanthin may protect against UVB radiation-induced corneal disorders by inhibiting expression of proinflammatory factors, TNF-α, and VEGF and by blocking polymorphonuclear leukocyte infiltration. Full article
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Article
Pinnisterols A–C, New 9,11-Secosterols from a Gorgonian Pinnigorgia sp.
by Yu-Chia Chang, Liang-Mou Kuo, Tsong-Long Hwang, Jessica Yeh, Zhi-Hong Wen, Lee-Shing Fang, Yang-Chang Wu, Chan-Shing Lin, Jyh-Horng Sheu and Ping-Jyun Sung
Mar. Drugs 2016, 14(1), 12; https://doi.org/10.3390/md14010012 - 07 Jan 2016
Cited by 17 | Viewed by 4931
Abstract
Three new 9,11-secosterols, pinnisterols A–C (13), were isolated from a gorgonian coral Pinnigorgia sp., collected off the waters of Taiwan. The structures of these compounds were elucidated on the basis of spectroscopic methods. The new sterols 1 and 3 [...] Read more.
Three new 9,11-secosterols, pinnisterols A–C (13), were isolated from a gorgonian coral Pinnigorgia sp., collected off the waters of Taiwan. The structures of these compounds were elucidated on the basis of spectroscopic methods. The new sterols 1 and 3 displayed significant inhibitory effects on the generation of superoxide anions and the release of elastase by human neutrophils, and sterol 1 was found to show moderate cytotoxicity in hepatic stellate cells (HSCs). Full article
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Article
Bioactive Polycyclic Quinones from Marine Streptomyces sp. 182SMLY
by Ying Liang, Xin Xie, Lu Chen, Shilun Yan, Xuewei Ye, Komal Anjum, Haocai Huang, Xiaoyuan Lian and Zhizhen Zhang
Mar. Drugs 2016, 14(1), 10; https://doi.org/10.3390/md14010010 - 06 Jan 2016
Cited by 56 | Viewed by 6095
Abstract
Chemical investigation of the cultures of marine Streptomyces sp. 182SMLY led to the discovery of two new polycyclic anthraquinones, which were elucidated as N-acetyl-N-demethylmayamycin (1) and streptoanthraquinone A (2) based on the extensive spectroscopic analysis including [...] Read more.
Chemical investigation of the cultures of marine Streptomyces sp. 182SMLY led to the discovery of two new polycyclic anthraquinones, which were elucidated as N-acetyl-N-demethylmayamycin (1) and streptoanthraquinone A (2) based on the extensive spectroscopic analysis including 2D NMR, HRESIMS, and an electronic circular dichroism (ECD) calculation. Both anthraquinones remarkably suppressed the proliferation of four different glioma cell lines with IC50 values in a range from 0.5 to 7.3 μM and induced apoptosis in the glioma cells. The ratios of IC50 for normal human astrocytes to IC50 for glioma cells were 6.4–53 for 1 and >14–31 for 2. N-acetyl-N-demethylmayamycin (1) also inhibited the growth of methicillin-resistant Staphylococcus aureus with MIC 20.0 μM. Full article
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Article
Recombinant Expression and Characterization of α-Conotoxin LvIA in Escherichia coli
by Xiaopeng Zhu, Jianpeng Bi, Jinpeng Yu, Xiaodan Li, Yaning Zhang, Dongting Zhangsun and Sulan Luo
Mar. Drugs 2016, 14(1), 11; https://doi.org/10.3390/md14010011 - 05 Jan 2016
Cited by 18 | Viewed by 6236
Abstract
α-Conotoxin LvIA is derived from Conus lividus, native to Hainan, and is the most selective inhibitor of α3β2 nicotinic acetylcholine receptors (nAChRs) known to date. In this study, an efficient approach for the production of recombinant α-Conotoxin LvIA is described. Tandem repeats [...] Read more.
α-Conotoxin LvIA is derived from Conus lividus, native to Hainan, and is the most selective inhibitor of α3β2 nicotinic acetylcholine receptors (nAChRs) known to date. In this study, an efficient approach for the production of recombinant α-Conotoxin LvIA is described. Tandem repeats of a LvIA gene fragment were constructed and fused with a KSI gene and a His6 tag in a Escherichia coli (E. coli) expression vector pET-31b(+). The recombinant plasmids were transformed into E. coli and were found to express well. The KSI-(LvIA)n-His6 fusion protein was purified by metal affinity chromatography and then cleaved with CNBr to release recombinant LvIA (rLvIA). High yields of fusion protein ranging from 100 to 500 mg/L culture were obtained. The pharmacological profile of rLvIA was determined by two-electrode voltage-clamp electrophysiology in Xenopus laevis oocytes expressing rat nAChR subtypes. The rLvIA antagonized the α3β2 nAChR subtype selectively with a nano-molar IC50. The rLvIA was analgesic in a mouse hot-plate test model of pain. Overall, this study provides an effective method to synthesize α-conotoxin LvIA in an E. coli recombinant expression system, and this approach could be useful to obtain active conopeptides in large quantity and at low cost. Full article
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Article
Specific Metabolites in a Phaeodactylum tricornutum Strain Isolated from Western Norwegian Fjord Water
by Siv Kristin Prestegard, Svein Rune Erga, Pia Steinrücken, Svein Are Mjøs, Gjert Knutsen and Jens Rohloff
Mar. Drugs 2016, 14(1), 9; https://doi.org/10.3390/md14010009 - 30 Dec 2015
Cited by 20 | Viewed by 6336
Abstract
We have searched for special characteristics in growth, protein expression, fatty acids and volatile organic compounds (VOCs) in a local Phaeodactylum tricornutum Bohlin strain (Bergen Marine Biobank), by comparing it with a common accession strain (CCAP). Differences in growth and expressed proteins were [...] Read more.
We have searched for special characteristics in growth, protein expression, fatty acids and volatile organic compounds (VOCs) in a local Phaeodactylum tricornutum Bohlin strain (Bergen Marine Biobank), by comparing it with a common accession strain (CCAP). Differences in growth and expressed proteins were detected between the BMB strain and the CCAP strain, and the BMB strain reached the highest cell densities under the given growth conditions. Fatty acid (FA) analyses showed highest relative eicosapentaenoic acid (EPA) levels in the exponential phase (25.73% and 28.31%), and highest levels of palmitoleic acid (16:1 n-7) in the stationary phase (46.36% and 43.66%) in the BMB and CCAP strain, respectively. The most striking finding of the VOCs analyses was the relatively high levels of ectocarpene, 6-((1E)-butenyl)-1,4-cycloheptadiene, hormosirene, and desmarestene and structurally related compounds, which were exclusively detected in the BMB strain. Many of the VOCs detected in the CCAP and, in particular, in the BMB strain have been reported as antimicrobial agents. We suggest that the array of pheromones and antimicrobial substances could be part of an allelopathic strategy of the BMB strain, dominated by oval cells, thus reflecting the benthic life stage of this morphological form. These findings show the potential for bioactive metabolites in the BMB strain. Full article
(This article belongs to the Special Issue Metabolites in Diatoms)
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Article
Structures and Activity of New Anabaenopeptins Produced by Baltic Sea Cyanobacteria
by Lisa Spoof, Agata Błaszczyk, Jussi Meriluoto, Marta Cegłowska and Hanna Mazur-Marzec
Mar. Drugs 2016, 14(1), 8; https://doi.org/10.3390/md14010008 - 30 Dec 2015
Cited by 70 | Viewed by 7504
Abstract
Anabaenopeptins, bioactive cyclic hexapeptides, were isolated by preparative reversed-phase high performance liquid chromatography from an extract of Baltic Sea cyanobacterial bloom material composed of Nodularia spumigena (50%), Aphanizomenon flos-aquae (40%) and Dolichospermum spp. (10%). Five new anabaenopeptins and nine previously known anabaenopeptins were [...] Read more.
Anabaenopeptins, bioactive cyclic hexapeptides, were isolated by preparative reversed-phase high performance liquid chromatography from an extract of Baltic Sea cyanobacterial bloom material composed of Nodularia spumigena (50%), Aphanizomenon flos-aquae (40%) and Dolichospermum spp. (10%). Five new anabaenopeptins and nine previously known anabaenopeptins were isolated, and their putative structures were determined by tandem mass spectrometry. The activity of the peptides against carboxypeptidase A and protein phosphatase 1 as well as chymotrypsin, trypsin and thrombin was tested. All anabaenopeptins inhibited carboxypeptidase A (apart from one anabaenopeptin variant) and protein phosphatase 1 with varying potency, but no inhibition against chymotrypsin, trypsin and thrombin was observed. Full article
(This article belongs to the Special Issue Compounds from Cyanobacteria)
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Article
Determination of FVIIa-sTF Inhibitors in Toxic Microcystis Cyanobacteria by LC-MS Technique
by Andrea Roxanne J. Anas, Anna Nakajima, Chiaki Naruse, Mineka Tone, Hirohiko Asukabe and Ken-ichi Harada
Mar. Drugs 2016, 14(1), 7; https://doi.org/10.3390/md14010007 - 30 Dec 2015
Cited by 9 | Viewed by 5957
Abstract
The blood coagulation cascade involves the human coagulation factors thrombin and an activated factor VII (fVIIa). Thrombin and fVIIa are vitamin-K-dependent clotting factors associated with bleeding, bleeding complications and disorders. Thrombin and fVIIa cause excessive bleeding when treated with vitamin-K antagonists. In this [...] Read more.
The blood coagulation cascade involves the human coagulation factors thrombin and an activated factor VII (fVIIa). Thrombin and fVIIa are vitamin-K-dependent clotting factors associated with bleeding, bleeding complications and disorders. Thrombin and fVIIa cause excessive bleeding when treated with vitamin-K antagonists. In this research, we explored different strains of toxic Microcystis aeruginosa and cyanobacteria blooms for the probable fVIIa-soluble Tissue Factor (fVIIa-sTF) inhibitors. The algal cells were subjected to acidification, and reverse phase (ODS) chromatography-solid phase extraction eluted by water to 100% MeOH with 20%-MeOH increments except for M. aeruginosa NIES-89, from the National Institute for Environmental Studies (NIES), which was eluted with 5%-MeOH increments as an isolation procedure to separate aeruginosins 89A and B from co-eluting microcystins. The 40%–80% MeOH fractions of the cyanobacterial extract are active against fVIIa-sTF. The fVIIa-sTF active fractions from cultured cyanobacteria and cyanobacteria blooms were subjected to liquid chromatography-mass spectrometry (LC-MS). The 60% MeOH fraction of M. aeruginosa K139 exhibited an m/z 603 [M + H]+ attributed to aeruginosin K139, and the 40% MeOH fraction of M. aeruginosa NIES-89 displayed ions with m/z 617 [M − SO3 + H]+ and m/z [M + H]+ 717, which attributed to aeruginosin 89. Aeruginosins 102A/B and 298A/B were also observed from other toxic strains of M. aeruginosa with positive fVIIa-sTF inhibitory activity. The active fractions contained cyanobacterial peptides of the aeruginosin class as fVIIa-sTF inhibitors detected by LC-MS. Full article
(This article belongs to the Special Issue Marine Anticoagulants and Antithrombotics)
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1534 KiB  
Article
Structural and Immunological Activity Characterization of a Polysaccharide Isolated from Meretrix meretrix Linnaeus
by Li Li, Heng Li, Jianying Qian, Yongfeng He, Jialin Zheng, Zhenming Lu, Zhenghong Xu and Jinsong Shi
Mar. Drugs 2016, 14(1), 6; https://doi.org/10.3390/md14010006 - 29 Dec 2015
Cited by 13 | Viewed by 5463
Abstract
Polysaccharides from marine clams perform various biological activities, whereas information on structure is scarce. Here, a water-soluble polysaccharide MMPX-B2 was isolated from Meretrix meretrix Linnaeus. The proposed structure was deduced through characterization and its immunological activity was investigated. MMPX-B2 consisted of d-glucose [...] Read more.
Polysaccharides from marine clams perform various biological activities, whereas information on structure is scarce. Here, a water-soluble polysaccharide MMPX-B2 was isolated from Meretrix meretrix Linnaeus. The proposed structure was deduced through characterization and its immunological activity was investigated. MMPX-B2 consisted of d-glucose and d-galctose residues at a molar ratio of 3.51:1.00. The average molecular weight of MMPX-B2 was 510 kDa. This polysaccharide possessed a main chain of (1→4)-linked-α-d-glucopyranosyl residues, partially substituted at the C-6 position by a few terminal β-d-galactose residues or branched chains consisting of (1→3)-linked β-d-galactose residues. Preliminary immunological tests in vitro showed that MMPX-B2 could stimulate the murine macrophages to release various cytokines, and the structure-activity relationship was then established. The present study demonstrated the potential immunological activity of MMPX-B2, and provided references for studying the active ingredients in M. meretrix. Full article
(This article belongs to the Collection Marine Polysaccharides)
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2961 KiB  
Article
Characterization and Comparison of the Structural Features, Immune-Modulatory and Anti-Avian Influenza Virus Activities Conferred by Three Algal Sulfated Polysaccharides
by Lin Song, Xiaolin Chen, Xiaodong Liu, Fubo Zhang, Linfeng Hu, Yang Yue, Kecheng Li and Pengcheng Li
Mar. Drugs 2016, 14(1), 4; https://doi.org/10.3390/md14010004 - 29 Dec 2015
Cited by 61 | Viewed by 7179
Abstract
Three marine macroalgae, i.e., Grateloupia filicina, Ulva pertusa and Sargassum qingdaoense, were selected as the deputies of Rhodophyta, Chlorophyta and Ochrophyta for comparative analysis of the molecular structures and biological activities of sulfated polysaccharides (SP). The ratio of water-soluble polysaccharides, [...] Read more.
Three marine macroalgae, i.e., Grateloupia filicina, Ulva pertusa and Sargassum qingdaoense, were selected as the deputies of Rhodophyta, Chlorophyta and Ochrophyta for comparative analysis of the molecular structures and biological activities of sulfated polysaccharides (SP). The ratio of water-soluble polysaccharides, the monosaccharide composition and the sulfated contents of three extracted SPs were determined, and their structures were characterized by Fourier transformation infrared spectroscopy. In addition, biological activity analysis showed that all three SPs had immune-modulatory activity both in vitro and in vivo, and SPs from S. qingdaoense had the best effect. Further bioassays showed that three SPs could not only enhance the immunity level stimulated by inactivated avian influenza virus (AIV) in vivo but also significantly inhibited the activity of activated AIV (H9N2 subtype) in vitro. G. filicina SP exhibited the strongest anti-AIV activity. These results revealed the variations in structural features and bioactivities among three SPs and indicated the potential adjuvants for immune-enhancement and anti-AIV. Full article
(This article belongs to the Collection Marine Polysaccharides)
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903 KiB  
Review
New Drugs from Marine Organisms in Alzheimer’s Disease
by Patrizia Russo, Aliaksei Kisialiou, Palma Lamonaca, Rossana Moroni, Giulia Prinzi and Massimo Fini
Mar. Drugs 2016, 14(1), 5; https://doi.org/10.3390/md14010005 - 25 Dec 2015
Cited by 55 | Viewed by 9219
Abstract
Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder. Current approved drugs may only ameliorate symptoms in a restricted number of patients and for a restricted period of time. Currently, there is a translational research challenge into identifying the new effective drugs and their [...] Read more.
Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder. Current approved drugs may only ameliorate symptoms in a restricted number of patients and for a restricted period of time. Currently, there is a translational research challenge into identifying the new effective drugs and their respective new therapeutic targets in AD and other neurodegenerative disorders. In this review, selected examples of marine-derived compounds in neurodegeneration, specifically in AD field are reported. The emphasis has been done on compounds and their possible relevant biological activities. The proposed drug development paradigm and current hypotheses should be accurately investigated in the future of AD therapy directions although taking into account successful examples of such approach represented by Cytarabine, Trabectedin, Eribulin and Ziconotide. We review a complexity of the translational research for such a development of new therapies for AD. Bryostatin is a prominent candidate for the therapy of AD and other types of dementia in humans. Full article
(This article belongs to the Special Issue Marine Compounds and Their Application in Neurological Disorders)
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2386 KiB  
Article
The Structure-Activity Relationship between Marine Algae Polysaccharides and Anti-Complement Activity
by Weihua Jin, Wenjing Zhang, Hongze Liang and Quanbin Zhang
Mar. Drugs 2016, 14(1), 3; https://doi.org/10.3390/md14010003 - 25 Dec 2015
Cited by 45 | Viewed by 6598
Abstract
In this study, 33 different polysaccharides were prepared to investigate the structure-activity relationships between the polysaccharides, mainly from marine algae, and anti-complement activity in the classical pathway. Factors considered included extraction methods, fractionations, molecular weight, molar ratio of galactose to fucose, sulfate, uronic [...] Read more.
In this study, 33 different polysaccharides were prepared to investigate the structure-activity relationships between the polysaccharides, mainly from marine algae, and anti-complement activity in the classical pathway. Factors considered included extraction methods, fractionations, molecular weight, molar ratio of galactose to fucose, sulfate, uronic acid (UA) content, linkage, branching, and the type of monosaccharide. It was shown that the larger the molecular weights, the better the activities. The molar ratio of galactose (Gal) to fucose (Fuc) was a positive factor at a concentration lower than 10 µg/mL, while it had no effect at a concentration more than 10 µg/mL. In addition, sulfate was necessary; however, the sulfate content, the sulfate pattern, linkage and branching had no effect at a concentration of more than 10 µg/mL. Moreover, the type of monosaccharide had no effect. Laminaran and UA fractions had no activity; however, they could reduce the activity by decreasing the effective concentration of the active composition when they were mixed with the active compositions. The effect of the extraction methods could not be determined. Finally, it was observed that sulfated galactofucan showed good anti-complement activity after separation. Full article
(This article belongs to the Special Issue Marine Glycoconjugates)
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4422 KiB  
Article
In Vitro and in Vivo Anticancer Activity of Pardaxin against Proliferation and Growth of Oral Squamous Cell Carcinoma
by Yifan Han, Zhibin Cui, Yen-Hsing Li, Wei-Hsuan Hsu and Bao-Hong Lee
Mar. Drugs 2016, 14(1), 2; https://doi.org/10.3390/md14010002 - 23 Dec 2015
Cited by 44 | Viewed by 5736
Abstract
Pardaxin (H-GFFALIPKIISSPLFKTLLSAVGSALSSSGGQE-OH), a 33-amino-acid polypeptide, is an antimicrobial peptide (AMP) isolated from the marine fish species Pardachirus marmoratus. Pardaxin shows antibacterial and antitumor activities. However, pardaxin-induced inhibition of oral cancer and the mechanism of tumor reduction in buccal pouch carcinogenesis after pardaxin [...] Read more.
Pardaxin (H-GFFALIPKIISSPLFKTLLSAVGSALSSSGGQE-OH), a 33-amino-acid polypeptide, is an antimicrobial peptide (AMP) isolated from the marine fish species Pardachirus marmoratus. Pardaxin shows antibacterial and antitumor activities. However, pardaxin-induced inhibition of oral cancer and the mechanism of tumor reduction in buccal pouch carcinogenesis after pardaxin painting remain undetermined. Additionally, the toxic effects of pardaxin on normal tissue remain unclear. The present study investigated the anticancer activity of pardaxin in oral squamous cell carcinoma (OSCC) cells in the hamster buccal pouch model with or without 7,12-dimethylbenz[a]anthracene (DMBA) pretreatment. This is the first study to confirm the effects of pardaxin on normal tissue and its nontoxic effects in vivo. Cell viability assays and colony formation tests in OSCC cell lines (SCC-4) demonstrated that pardaxin reduced cell viability in a dose-dependent manner. Immunofluorescence staining of cleaved caspase-3 in SCC-4 cells revealed that expression of activated caspase-3 in SCC-4 cells significantly increased after 24-h treatment with pardaxin. Additionally, a cell cycle analysis indicated that pardaxin treatment resulted in the cell cycle arrest of SCC-4 cells in the G2/M phase, thereby limiting cell proliferation. Furthermore, pardaxin treatment substantially alleviated carcinogenesis in the DMBA-induced hamster buccal pouch model by lowering prostaglandin E2 levels. These results suggest that pardaxin is a potential marine drug for adjuvant chemotherapy for human OSCC and oral cancer. Full article
(This article belongs to the Special Issue Synthesis of Antitumor Marine Alkaloids and Related Analogues)
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1124 KiB  
Review
Aeroplysinin-1, a Sponge-Derived Multi-Targeted Bioactive Marine Drug
by Javier A. García-Vilas, Beatriz Martínez-Poveda, Ana R. Quesada and Miguel Ángel Medina
Mar. Drugs 2016, 14(1), 1; https://doi.org/10.3390/md14010001 - 22 Dec 2015
Cited by 43 | Viewed by 7352
Abstract
Organisms lacking external defense mechanisms have developed chemical defense strategies, particularly through the production of secondary metabolites with antibiotic or repellent effects. Secondary metabolites from marine organisms have proven to be an exceptionally rich source of small molecules with pharmacological activities potentially beneficial [...] Read more.
Organisms lacking external defense mechanisms have developed chemical defense strategies, particularly through the production of secondary metabolites with antibiotic or repellent effects. Secondary metabolites from marine organisms have proven to be an exceptionally rich source of small molecules with pharmacological activities potentially beneficial to human health. (+)-Aeroplysinin-1 is a secondary metabolite isolated from marine sponges with a wide spectrum of bio-activities. (+)-Aeroplysinin-1 has potent antibiotic effects on Gram-positive bacteria and several dinoflagellate microalgae causing toxic blooms. In preclinical studies, (+)-aeroplysinin-1 has been shown to have promising anti-inflammatory, anti-angiogenic and anti-tumor effects. Due to its versatility, (+)-aeroplysinin-1 might have a pharmaceutical interest for the treatment of different pathologies. Full article
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