Marine Drugs

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Open AccessArticle

Synthesis of Natural O-Linked Carba-Disaccharides, (+)- and (−)-Pericosine E, and Their Analogues as α-Glucosidase Inhibitors

by Yoshihide Usami, Koji Mizuki, Rikiya Kawahata, Makio Shibano, Atsuko Sekine, Hiroki Yoneyama and Shinya Harusawa

Mar. Drugs 2017, 15(1), 22; https://doi.org/10.3390/md15010022 - 23 Jan 2017

Cited by 8 | Viewed by 5571

Abstract

Pericosine E (6), a metabolite of Periconia byssoides OUPS-N133 was originally isolated from the sea hare Aplysia kurodai, which exists as an enantiomeric mixture in nature. The enantiospecific syntheses of both enantiomers of Periconia byssoides OUPS-N133 has been achieved, along [...] Read more.

Pericosine E (6), a metabolite of Periconia byssoides OUPS-N133 was originally isolated from the sea hare Aplysia kurodai, which exists as an enantiomeric mixture in nature. The enantiospecific syntheses of both enantiomers of Periconia byssoides OUPS-N133 has been achieved, along with six stereoisomers, using a common simple synthetic strategy. For these efficient syntheses, highly regio- and steroselective processes for the preparation of bromohydrin and anti-epoxide intermediates were applied. In order to access the unique O-linked carbadisaccharide structure, coupling of chlorohydrin as a donor and anti-epoxide as an acceptor was achieved using catalytic BF₃·Et₂O. Most of the synthesized compounds exhibited selectively significant inhibitory activity against α-glycosidase derived from yeast. The strongest analog showed almost 50 times the activity of the positive control, deoxynojirimycin. Full article

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Open AccessArticle

Klyflaccicembranols A–I, New Cembranoids from the Soft Coral Klyxum flaccidum

by Atallah F. Ahmed, Chia-Ruei Tsai, Chiung-Yao Huang, Sheng-Yang Wang and Jyh-Horng Sheu

Mar. Drugs 2017, 15(1), 23; https://doi.org/10.3390/md15010023 - 21 Jan 2017

Cited by 14 | Viewed by 5988

Abstract

New cembranoids klyflaccicembranols A–I (1–9), along with gibberosene D (10), have been isolated from the organic extract of a Formosan soft coral Klyxum flaccidum. Their structures were established by extensive spectroscopic analyses, including 2D NMR spectroscopy, [...] Read more.

New cembranoids klyflaccicembranols A–I (1–9), along with gibberosene D (10), have been isolated from the organic extract of a Formosan soft coral Klyxum flaccidum. Their structures were established by extensive spectroscopic analyses, including 2D NMR spectroscopy, and spectral data comparison with related structures. The cytotoxicity of the isolated metabolites, as well as their nitric oxide (NO) inhibitory activity, were evaluated and reported. Metabolites 2, 4, 6, 8 and 9 were found to exhibit variable activities against a limited panel of cancer cell lines in a range of IC₅₀ 16.5–49.4 μM. Among the tested cembranoids, compounds 4, 5, 6, and 9 significantly inhibited NO production in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages at a dose of 50 μg/mL. Full article

(This article belongs to the Collection Bioactive Compounds from Marine Invertebrates)

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Open AccessArticle

Molecular Characterization of Voltage-Gated Sodium Channels and Their Relations with Paralytic Shellfish Toxin Bioaccumulation in the Pacific Oyster Crassostrea gigas

by Floriane Boullot, Justine Castrec, Adeline Bidault, Natanael Dantas, Laura Payton, Mickael Perrigault, Damien Tran, Zouher Amzil, Pierre Boudry, Philippe Soudant, Hélène Hégaret and Caroline Fabioux

Mar. Drugs 2017, 15(1), 21; https://doi.org/10.3390/md15010021 - 19 Jan 2017

Cited by 14 | Viewed by 7490

Abstract

Paralytic shellfish toxins (PST) bind to voltage-gated sodium channels (Nav) and block conduction of action potential in excitable cells. This study aimed to (i) characterize Nav sequences in Crassostrea gigas and (ii) investigate a putative relation between Nav and PST-bioaccumulation in oysters. The [...] Read more.

Paralytic shellfish toxins (PST) bind to voltage-gated sodium channels (Nav) and block conduction of action potential in excitable cells. This study aimed to (i) characterize Nav sequences in Crassostrea gigas and (ii) investigate a putative relation between Nav and PST-bioaccumulation in oysters. The phylogenetic analysis highlighted two types of Nav in C. gigas: a Nav1 (CgNav1) and a Nav2 (CgNav2) with sequence properties of sodium-selective and sodium/calcium-selective channels, respectively. Three alternative splice transcripts of CgNav1 named A, B and C, were characterized. The expression of CgNav1, analyzed by in situ hybridization, is specific to nervous cells and to structures corresponding to neuromuscular junctions. Real-time PCR analyses showed a strong expression of CgNav1A in the striated muscle while CgNav1B is mainly expressed in visceral ganglia. CgNav1C expression is ubiquitous. The PST binding site (domain II) of CgNav1 variants possess an amino acid Q that could potentially confer a partial saxitoxin (STX)-resistance to the channel. The CgNav1 genotype or alternative splicing would not be the key point determining PST bioaccumulation level in oysters. Full article

(This article belongs to the Special Issue Marine Neurotoxins)

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Open AccessArticle

Quantitative Proteomic Profiling of Tachyplesin I Targets in U251 Gliomaspheres

by Xuan Li, Jianguo Dai, Yongjun Tang, Lulu Li and Gang Jin

Mar. Drugs 2017, 15(1), 20; https://doi.org/10.3390/md15010020 - 18 Jan 2017

Cited by 19 | Viewed by 6654

Abstract

Tachyplesin I is a cationic peptide isolated from hemocytes of the horseshoe crab and its anti-tumor activity has been demonstrated in several tumor cells. However, there is limited information providing the global effects and mechanisms of tachyplesin I on glioblastoma multiforme (GBM). Here, [...] Read more.

Tachyplesin I is a cationic peptide isolated from hemocytes of the horseshoe crab and its anti-tumor activity has been demonstrated in several tumor cells. However, there is limited information providing the global effects and mechanisms of tachyplesin I on glioblastoma multiforme (GBM). Here, by using two complementary proteomic strategies (2D-DIGE and dimethyl isotope labeling-based shotgun proteomics), we explored the effect of tachyplesin I on the proteome of gliomaspheres, a three-dimensional growth model formed by a GBM cell line U251. In total, the expression levels of 192 proteins were found to be significantly altered by tachyplesin I treatment. Gene ontology (GO) analysis revealed that many of them were cytoskeleton proteins and lysosomal acid hydrolases, and the mostly altered biological process was related to cellular metabolism, especially glycolysis. Moreover, we built protein–protein interaction network of these proteins and suggested the important role of DNA topoisomerase 2-alpha (TOP2A) in the signal-transduction cascade of tachyplesin I. In conclusion, we propose that tachyplesin I might down-regulate cathepsins in lysosomes and up-regulate TOP2A to inhibit migration and promote apoptosis in glioma, thus contribute to its anti-tumor function. Our results suggest tachyplesin I is a potential candidate for treatment of glioma. Full article

(This article belongs to the Special Issue Marine Compounds as Modulators of Autophagy and Lysosomal Activity)

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Open AccessArticle

New Enzyme-Inhibitory Triterpenoid from Marine Macro Brown Alga Padina boergesenii Allender & Kraft

by Liaqat Ali, Abdul Latif Khan, Muhammad Al-Broumi, Rashid Al-Harrasi, Lubna Al-Kharusi, Javid Hussain and Ahmed Al-Harrasi

Mar. Drugs 2017, 15(1), 19; https://doi.org/10.3390/md15010019 - 18 Jan 2017

Cited by 13 | Viewed by 5920

Abstract

In continuation to our study of the chemical and biological potential of the secondary metabolites isolated from Omani seaweeds, we investigated a marine brown alga, Padina boergesenii. The phytochemical investigation resulted in the isolation of a new secondary metabolite, padinolic acid ( [...] Read more.

In continuation to our study of the chemical and biological potential of the secondary metabolites isolated from Omani seaweeds, we investigated a marine brown alga, Padina boergesenii. The phytochemical investigation resulted in the isolation of a new secondary metabolite, padinolic acid (1), along with some other semi-pure fractions and sub-fractions. The planar structure was confirmed through MS and NMR (1D and 2D) spectral data. The NOESY experiments coupled with the biogenetic consideration were helpful in assigning the stereochemistry in the molecule. Compound 1 was subjected to enzyme inhibition studies using urease, lipid peroxidase, and alpha-glucosidase enzymes. Compound 1 showed low to moderate α-glucosidase and urease enzyme inhibition, respectively, and moderate anti-lipid peroxidation activities. The current study indicates the potential of this seaweed and provides the basis for further investigation. Full article

(This article belongs to the Special Issue Enzyme Inhibitors of Marine Origin)

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Open AccessCommunication

Asymmetric Total Synthesis of Ieodomycin B

by Shuangjie Lin, Jianting Zhang, Zhibin Zhang, Tianxiang Xu, Shuangping Huang and Xiaoji Wang

Mar. Drugs 2017, 15(1), 17; https://doi.org/10.3390/md15010017 - 18 Jan 2017

Cited by 11 | Viewed by 5666

Abstract

Ieodomycin B, which shows in vitro antimicrobial activity, was isolated from a marine Bacillus species. A novel asymmetric total synthetic approach to ieodomycin B using commercially available geraniol was achieved. The approach involves the generation of 1,3-trans-dihydroxyl at C-3 and C-5 [...] Read more.

Ieodomycin B, which shows in vitro antimicrobial activity, was isolated from a marine Bacillus species. A novel asymmetric total synthetic approach to ieodomycin B using commercially available geraniol was achieved. The approach involves the generation of 1,3-trans-dihydroxyl at C-3 and C-5 positions via a Crimmins-modified Evans aldol reaction and a chelation-controlled Mukaiyama aldol reaction of a p-methoxybenzyl-protected aldehyde, as well as the generation of a lactone ring in a deprotection–lactonization one-pot reaction. Full article

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

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Open AccessReview

Marine Antibody–Drug Conjugates: Design Strategies and Research Progress

by Yu-Jie Wang, Yu-Yan Li, Xiao-Yu Liu, Xiao-Ling Lu, Xin Cao and Bing-Hua Jiao

Mar. Drugs 2017, 15(1), 18; https://doi.org/10.3390/md15010018 - 13 Jan 2017

Cited by 52 | Viewed by 10209

Abstract

Antibody–drug conjugates (ADCs), constructed with monoclonal antibodies (mAbs), linkers, and natural cytotoxins, are innovative drugs developed for oncotherapy. Owing to the distinctive advantages of both chemotherapy drugs and antibody drugs, ADCs have obtained enormous success during the past several years. The development of [...] Read more.

Antibody–drug conjugates (ADCs), constructed with monoclonal antibodies (mAbs), linkers, and natural cytotoxins, are innovative drugs developed for oncotherapy. Owing to the distinctive advantages of both chemotherapy drugs and antibody drugs, ADCs have obtained enormous success during the past several years. The development of highly specific antibodies, novel marine toxins’ applications, and innovative linker technologies all accelerate the rapid R&D of ADCs. Meanwhile, some challenges remain to be solved for future ADCs. For instance, varieties of site-specific conjugation have been proposed for solving the inhomogeneity of DARs (Drug Antibody Ratios). In this review, the usages of various natural toxins, especially marine cytotoxins, and the development strategies for ADCs in the past decade are summarized. Representative ADCs with marine cytotoxins in the pipeline are introduced and characterized with their new features, while perspective comments for future ADCs are proposed. Full article

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Open AccessArticle

Preparation of Antioxidant Peptides from Salmon Byproducts with Bacterial Extracellular Proteases

by Ribang Wu, Leilei Chen, Dan Liu, Jiafeng Huang, Jiang Zhang, Xiao Xiao, Ming Lei, Yuelin Chen and Hailun He

Mar. Drugs 2017, 15(1), 4; https://doi.org/10.3390/md15010004 - 11 Jan 2017

Cited by 42 | Viewed by 7053

Abstract

Bacterial extracellular proteases from six strains of marine bacteria and seven strains of terrestrial bacteria were prepared through fermentation. Proteases were analyzed through substrate immersing zymography and used to hydrolyze the collagen and muscle proteins from a salmon skin byproduct, respectively. Collagen could [...] Read more.

Bacterial extracellular proteases from six strains of marine bacteria and seven strains of terrestrial bacteria were prepared through fermentation. Proteases were analyzed through substrate immersing zymography and used to hydrolyze the collagen and muscle proteins from a salmon skin byproduct, respectively. Collagen could be degraded much more easily than muscle protein, but it commonly showed weaker antioxidant capability. The hydrolysate of muscle proteins was prepared with crude enzymes from Pseudoalteromonas sp. SQN1 displayed the strongest activity of antioxidant in DPPH and hydroxyl radical scavenging assays (74.06% ± 1.14% and 69.71% ± 1.97%), but did not perform well in Fe²⁺ chelating assay. The antioxidant fractions were purified through ultrafiltration, cation exchange chromatography, and size exclusion chromatography gradually, and the final purified fraction U2-S2-I displayed strong activity of antioxidant in DPPH, hydroxyl radical scavenging assays (IC₅₀ = 0.263 ± 0.018 mg/mL and 0.512 ± 0.055 mg/mL), and oxygen radical absorption capability assay (1.960 ± 0.381 mmol·TE/g). The final purified fraction U2-S2-I possessed the capability to protect plasmid DNA against the damage of hydroxyl radical and its effect was similar to that of the original hydrolysis product. It indicated that U2-S2-I might be the major active fraction of the hydrolysate. This study proved that bacterial extracellular proteases could be utilized in hydrolysis of a salmon byproduct. Compared with collagen, muscle proteins was an ideal material used as an enzymatic substrate to prepare antioxidant peptides. Full article

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

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Open AccessFeature PaperArticle

Dragmacidin G, a Bioactive Bis-Indole Alkaloid from a Deep-Water Sponge of the Genus Spongosorites

by Amy E. Wright, K. Brian Killday, Debopam Chakrabarti, Esther A. Guzmán, Dedra Harmody, Peter J. McCarthy, Tara Pitts, Shirley A. Pomponi, John K. Reed, Bracken F. Roberts, Carolina Rodrigues Felix and Kyle H. Rohde

Mar. Drugs 2017, 15(1), 16; https://doi.org/10.3390/md15010016 - 11 Jan 2017

Cited by 30 | Viewed by 10082

Abstract

A deep-water sponge of the genus Spongosorites has yielded a bis-indole alkaloid which we have named dragmacidin G. Dragmacidin G was first reported by us in the patent literature and has recently been reported by Hitora et al. from a sponge of the [...] Read more.

A deep-water sponge of the genus Spongosorites has yielded a bis-indole alkaloid which we have named dragmacidin G. Dragmacidin G was first reported by us in the patent literature and has recently been reported by Hitora et al. from a sponge of the genus Lipastrotheya. Dragmacidin G is the first in this series of compounds to have a pyrazine ring linking the two indole rings. It also has a rare N-(2-mercaptoethyl)-guanidine side chain. Dragmacidin G shows a broad spectrum of biological activity including inhibition of methicillin-resistant Staphylococcus aureus, Mycobacterium tuberculosis, Plasmodium falciparum, and a panel of pancreatic cancer cell lines. Full article

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Open AccessEditorial

Acknowledgement to Reviewers of Marine Drugs in 2016

by Marine Drugs Editorial Office

Mar. Drugs 2017, 15(1), 15; https://doi.org/10.3390/md15010015 - 11 Jan 2017

Cited by 1 | Viewed by 4250

Abstract

The editors of Marine Drugs would like to express their sincere gratitude to the following reviewers for assessing manuscripts in 2016. [...]
Full article

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Open AccessArticle

Time Course Exo-Metabolomic Profiling in the Green Marine Macroalga Ulva (Chlorophyta) for Identification of Growth Phase-Dependent Biomarkers

by Taghreed Alsufyani, Anne Weiss and Thomas Wichard

Mar. Drugs 2017, 15(1), 14; https://doi.org/10.3390/md15010014 - 10 Jan 2017

Cited by 41 | Viewed by 7948

Abstract

The marine green macroalga Ulva (Chlorophyta) lives in a mutualistic symbiosis with bacteria that influence growth, development, and morphogenesis. We surveyed changes in Ulva’s chemosphere, which was defined as a space where organisms interact with each other via compounds, such as infochemicals, [...] Read more.

The marine green macroalga Ulva (Chlorophyta) lives in a mutualistic symbiosis with bacteria that influence growth, development, and morphogenesis. We surveyed changes in Ulva’s chemosphere, which was defined as a space where organisms interact with each other via compounds, such as infochemicals, nutrients, morphogens, and defense compounds. Thereby, Ulva mutabilis cooperates with bacteria, in particular, Roseovarius sp. strain MS2 and Maribacter sp. strain MS6 (formerly identified as Roseobacter sp. strain MS2 and Cytophaga sp. strain MS6). Without this accompanying microbial flora, U. mutabilis forms only callus-like colonies. However, upon addition of the two bacteria species, in effect forming a tripartite community, morphogenesis can be completely restored. Under this strictly standardized condition, bioactive and eco-physiologically-relevant marine natural products can be discovered. Solid phase extracted waterborne metabolites were analyzed using a metabolomics platform, facilitating gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) analysis, combined with the necessary acquisition of biological metadata. Multivariate statistics of the GC-MS and LC-MS data revealed strong differences between Ulva’s growth phases, as well as between the axenic Ulva cultures and the tripartite community. Waterborne biomarkers, including glycerol, were identified as potential indicators for algal carbon source and bacterial-algal interactions. Furthermore, it was demonstrated that U. mutabilis releases glycerol that can be utilized for growth by Roseovarius sp. MS2. Full article

(This article belongs to the Special Issue Marine Natural Product Discovery: Innovative Strategies and Future Trends)

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Open AccessArticle

Biochemical and Structural Insights into a Novel Thermostable β-1,3-Galactosidase from Marinomonas sp. BSi20414

by Haitao Ding, Qian Zeng, Lili Zhou, Yong Yu and Bo Chen

Mar. Drugs 2017, 15(1), 13; https://doi.org/10.3390/md15010013 - 8 Jan 2017

Cited by 21 | Viewed by 5705

Abstract

A novel β-1,3-galactosidase, designated as MaBGA (β-galactosidase from Marinomonas sp. BSi20414), was successfully purified to homogeneity from Marinomonas sp. BSi20414 isolated from Arctic sea ice by ammonium sulfate precipitation and anion exchange chromatography, resulting in an 8.12-fold increase in specific activity and 9.9% [...] Read more.

A novel β-1,3-galactosidase, designated as MaBGA (β-galactosidase from Marinomonas sp. BSi20414), was successfully purified to homogeneity from Marinomonas sp. BSi20414 isolated from Arctic sea ice by ammonium sulfate precipitation and anion exchange chromatography, resulting in an 8.12-fold increase in specific activity and 9.9% recovery in total activity. MaBGA displayed its maximum activity at pH 6.0 and 60 °C, and maintained at least 90% of its initial activity over the pH range of 5.0–8.0 after incubating for 1 h. It also exhibited considerable thermal stability, which retained 76% of its initial activity after incubating at 50 °C for 6 h. In contrast to other β-galactosidases, MaBGA displayed strict substrate specificity, not only for the glycosyl group, but also for the linkage type. To better understand the structure–function relationship, the encoding gene of MaBGA was obtained and subject to bioinformatics analysis. Multiple alignments and phylogenetic analysis revealed that MaBGA belonged to the glycoside hydrolase family 42 and had closer genetic relationships with thermophilic β-galactosidases of extremophiles. With the aid of homology modeling and molecular docking, we proposed a reasonable explanation for the linkage selectivity of MaBGA from a structural perspective. On account of the robust stability and 1,3-linkage selectivity, MaBGA would be a promising candidate in the biosynthesis of galacto-oligosaccharide with β1–3 linkage. Full article

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

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Open AccessArticle

Excavatolide B Attenuates Rheumatoid Arthritis through the Inhibition of Osteoclastogenesis

by Yen-You Lin, Yen-Hsuan Jean, Hsin-Pai Lee, Sung-Chun Lin, Chieh-Yu Pan, Wu-Fu Chen, Shu-Fen Wu, Jui-Hsin Su, Kuan-Hao Tsui, Jyh-Horng Sheu, Ping-Jyun Sung and Zhi-Hong Wen

Mar. Drugs 2017, 15(1), 9; https://doi.org/10.3390/md15010009 - 6 Jan 2017

Cited by 25 | Viewed by 7560

Abstract

Osteoclasts are multinucleated giant cells of macrophage/monocyte lineage, and cell differentiation with the upregulation of osteoclast-related proteins is believed to play a major role in the destruction of the joints in the course of rheumatoid arthritis (RA). Pro-inflammatory cytokines, such as interleukin-17A (IL-17A) [...] Read more.

Osteoclasts are multinucleated giant cells of macrophage/monocyte lineage, and cell differentiation with the upregulation of osteoclast-related proteins is believed to play a major role in the destruction of the joints in the course of rheumatoid arthritis (RA). Pro-inflammatory cytokines, such as interleukin-17A (IL-17A) and macrophage colony-stimulating factor (M-CSF), can be overexpressed in RA and lead to osteoclastogenesis. In a previous study, we found that cultured-type soft coral-derived excavatolide B (Exc-B) exhibited anti-inflammatory properties. In the present study, we thus aimed to evaluate the anti-arthritic activity of Exc-B in in vitro and in vivo models. The results demonstrated that Exc-B inhibits LPS-induced multinucleated cell and actin ring formation, as well as TRAP, MMP-9, and cathepsin K expression. Additionally, Exc-B significantly attenuated the characteristics of RA in adjuvant (AIA) and type II collagen-induced arthritis (CIA) in rats. Moreover, Exc-B improved histopathological features, and reduced the number of TRAP-positive multinucleated cells in the in vivo AIA and CIA models. Immunohistochemical analysis showed that Exc-B attenuated the protein expression of cathepsin K, MMP-2, MMP-9, CD11b, and NFATc1 in ankle tissues of AIA and CIA rats. Level of interleukin-17A and macrophage colony-stimulating factor were also decreased by Exc-B. These findings strongly suggest that Exc-B could be of potential use as a therapeutic agent by inhibiting osteoclast differentiation in arthritis. Moreover, this study also illustrates the use of the anti-inflammatory marine compound, Exc-B, as a potential therapeutic strategy for RA. Full article

(This article belongs to the Collection Bioactive Compounds from Marine Invertebrates)

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Open AccessReview

Secondary Metabolites from the Marine Sponge Genus Phyllospongia

by Huawei Zhang, Menglian Dong, Hong Wang and Phillip Crews

Mar. Drugs 2017, 15(1), 12; https://doi.org/10.3390/md15010012 - 6 Jan 2017

Cited by 22 | Viewed by 6565

Abstract

Phyllospongia, one of the most common marine sponges in tropical and subtropical oceans, has been shown to be a prolific producer of natural products with a broad spectrum of biological activities. This review for the first time provides a comprehensive overview of [...] Read more.

Phyllospongia, one of the most common marine sponges in tropical and subtropical oceans, has been shown to be a prolific producer of natural products with a broad spectrum of biological activities. This review for the first time provides a comprehensive overview of secondary metabolites produced by Phyllospongia spp. over the 37 years from 1980 to 2016. Full article

(This article belongs to the Collection Bioactive Compounds from Marine Invertebrates)

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Open AccessArticle

Pinnisterols D–J, New 11-Acetoxy-9,11-secosterols with a 1,4-Quinone Moiety from Formosan Gorgonian Coral Pinnigorgia sp. (Gorgoniidae)

by Yu-Chia Chang, Tsong-Long Hwang, Liang-Mou Kuo and Ping-Jyun Sung

Mar. Drugs 2017, 15(1), 11; https://doi.org/10.3390/md15010011 - 6 Jan 2017

Cited by 16 | Viewed by 4883

Abstract

Seven new marine 11-acetoxy-9,11-secosterols, pinnisterols D–J (1–7), with a 1,4-quinone moiety, were discovered from the gorgonian coral Pinnigorgia sp. In this study, the structures of secosterols 1–7 were revealed by spectroscopic analysis. Bioactivity study showed that secosterol [...] Read more.

Seven new marine 11-acetoxy-9,11-secosterols, pinnisterols D–J (1–7), with a 1,4-quinone moiety, were discovered from the gorgonian coral Pinnigorgia sp. In this study, the structures of secosterols 1–7 were revealed by spectroscopic analysis. Bioactivity study showed that secosterol 1 treatment inhibited cell viability in a hepatic stellate cell line, HSC-T6, with an IC₅₀ value of 3.93 μM; and secosterols 2, 5, and 7 reduced elastase enzyme release, and 3, 5, and 7 decreased the production of superoxide anions from human neutrophils. Full article

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Open AccessArticle

Trichophycin A, a Cytotoxic Linear Polyketide Isolated from a Trichodesmium thiebautii Bloom

by Matthew J. Bertin, Paul G. Wahome, Paul V. Zimba, Haiyin He and Peter D. R. Moeller

Mar. Drugs 2017, 15(1), 10; https://doi.org/10.3390/md15010010 - 6 Jan 2017

Cited by 25 | Viewed by 6656

Abstract

In an effort to isolate and characterize bioactive secondary metabolites from Trichodesmium thiebautii blooms, collected cyanobacteria biomass was subjected to bioassay-guided extraction and fractionation using the human colon cancer cell line HCT-116, resulting in the isolation and subsequent structure characterization of a linear [...] Read more.

In an effort to isolate and characterize bioactive secondary metabolites from Trichodesmium thiebautii blooms, collected cyanobacteria biomass was subjected to bioassay-guided extraction and fractionation using the human colon cancer cell line HCT-116, resulting in the isolation and subsequent structure characterization of a linear polyketide trichophycin A (1). The planar structure of 1 was completed using 1D and 2D NMR spectroscopy and high-resolution electrospray ionization mass spectrometry (HRESIMS). Trichophycin A was moderately toxic against the murine neuroblastoma cell line Neuro-2A (EC₅₀: 6.5 μM) and HCT-116 cells (EC₅₀: 11.7 μM). Trichophycin A was significantly more cytotoxic than the previously isolated polyketides trichotoxin A and trichotoxin B. These cytotoxicity observations suggest that toxicity may be related to the polyol character of these polyketide compounds. Full article

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Open AccessArticle

The In Vitro and In Vivo Anti-Inflammatory Effects of a Phthalimide PPAR-γ Agonist

by Mingzhi Su, Jiafu Cao, Jin Huang, Sen Liu, Dong Soon Im, Jin-Wook Yoo and Jee H. Jung

Mar. Drugs 2017, 15(1), 7; https://doi.org/10.3390/md15010007 - 4 Jan 2017

Cited by 39 | Viewed by 8829

Abstract

Previously, the authors found that 4-hydroxy-2-(4-hydroxyphenethyl) isoindoline-1,3-dione (PD1) (a phthalimide analogue) bound to and activated peroxisome proliferator-activated receptor-γ (PPAR-γ). Since PPAR-γ suppresses inflammatory responses, the present study was undertaken to investigate the anti-inflammatory effects of PD1. In lipopolysaccharide (LPS)-stimulated murine [...] Read more.

Previously, the authors found that 4-hydroxy-2-(4-hydroxyphenethyl) isoindoline-1,3-dione (PD1) (a phthalimide analogue) bound to and activated peroxisome proliferator-activated receptor-γ (PPAR-γ). Since PPAR-γ suppresses inflammatory responses, the present study was undertaken to investigate the anti-inflammatory effects of PD1. In lipopolysaccharide (LPS)-stimulated murine RAW264.7 macrophages, PD1 suppressed the inductions of pro-inflammatory factors, including inducible nitric oxide synthase (iNOS), nitric oxide (NO), cyclooxygenase 2 (COX-2), tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Concomitantly, PD1 enhanced the expressions of anti-inflammatory factors, such as arginase-1 and interleukin-10 (IL-10), and suppressed LPS-evoked nuclear factor kappa B (NF-κB) p65 subunit phosphorylation in macrophages. In addition, PPAR-γ activated by PD1 was intensively translocated to the nucleus. These observations suggest that the anti-inflammatory mechanism of PD1 involves inhibition of the NF-κB pathway. In a subsequent in vivo animal experiment conducted using a carrageenan-induced acute inflammatory rat paw edema model, intraperitoneal injection of PD1 significantly reduced paw swelling. Histological analysis of rat paw tissue sections revealed less infiltration of immune cells in PD1-pretreated animals. These findings suggest that PD1 be viewed as a lead compound for the development of novel anti-inflammatory therapeutics. Full article

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Open AccessArticle

In vitro Anti-Thrombotic Activity of Extracts from Blacklip Abalone (Haliotis rubra) Processing Waste

by Hafiz Ansar Rasul Suleria, Barney M. Hines, Rama Addepalli, Wei Chen, Paul Masci, Glenda Gobe and Simone A. Osborne

Mar. Drugs 2017, 15(1), 8; https://doi.org/10.3390/md15010008 - 31 Dec 2016

Cited by 10 | Viewed by 7091

Abstract

Waste generated from the processing of marine organisms for food represents an underutilized resource that has the potential to provide bioactive molecules with pharmaceutical applications. Some of these molecules have known anti-thrombotic and anti-coagulant activities and are being investigated as alternatives to common [...] Read more.

Waste generated from the processing of marine organisms for food represents an underutilized resource that has the potential to provide bioactive molecules with pharmaceutical applications. Some of these molecules have known anti-thrombotic and anti-coagulant activities and are being investigated as alternatives to common anti-thrombotic drugs, like heparin and warfarin that have serious side effects. In the current study, extracts prepared from blacklip abalone (Haliotis rubra) processing waste, using food grade enzymes papain and bromelain, were found to contain sulphated polysaccharide with anti-thrombotic activity. Extracts were found to be enriched with sulphated polysaccharides and assessed for anti-thrombotic activity in vitro through heparin cofactor-II (HCII)-mediated inhibition of thrombin. More than 60% thrombin inhibition was observed in response to 100 μg/mL sulphated polysaccharides. Anti-thrombotic potential was further assessed as anti-coagulant activity in plasma and blood, using prothrombin time (PT), activated partial thromboplastin time (aPTT), and thromboelastography (TEG). All abalone extracts had significant activity compared with saline control. Anion exchange chromatography was used to separate extracts into fractions with enhanced anti-thrombotic activity, improving HCII-mediated thrombin inhibition, PT and aPTT almost 2-fold. Overall this study identifies an alternative source of anti-thrombotic molecules that can be easily processed offering alternatives to current anti-thrombotic agents like heparin. Full article

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

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Open AccessArticle

Merosesquiterpene Congeners from the Australian Sponge Hyrtios digitatus as Potential Drug Leads for Atherosclerosis Disease

by Huda A. Wahab, Ngoc B. Pham, Tengku S. Tengku Muhammad, John N. A. Hooper and Ronald J. Quinn

Mar. Drugs 2017, 15(1), 6; https://doi.org/10.3390/md15010006 - 27 Dec 2016

Cited by 11 | Viewed by 5591

Abstract

A study of the chemical constituents from the Australian Sponge Hyrtios digitatus has provided a perspective on the connection between the chemistry and biology of the puupehenones, a unique and unusual class of merosesquiterpenes. In this study, a new tetracyclic merosesquiterpene, 19-methoxy-9,15-ene-puupehenol ( [...] Read more.

A study of the chemical constituents from the Australian Sponge Hyrtios digitatus has provided a perspective on the connection between the chemistry and biology of the puupehenones, a unique and unusual class of merosesquiterpenes. In this study, a new tetracyclic merosesquiterpene, 19-methoxy-9,15-ene-puupehenol (1) was isolated from the marine sponge Hyrtios digitatus along with the known 20-methoxy-9,15-ene-puupehenol (2). Their structures were elucidated on the basis of spectroscopic data (¹H and ¹³C NMR) in combination with experimental electronic circular dichroism (ECD) data. Compounds 1 and 2 are active at 1.78 μM and 3.05 μM, respectively, on Scavenger Receptor-Class B Type 1 HepG2 (SR-B1 HepG2) stable cell lines, targeting atherosclerosis disease. Full article

(This article belongs to the Collection Bioactive Compounds from Marine Invertebrates)

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1877 KiB

Open AccessArticle

Structure-Based Design and Synthesis of a New Phenylboronic-Modified Affinity Medium for Metalloprotease Purification

by Shangyong Li, Linna Wang, Ximing Xu, Shengxiang Lin, Yuejun Wang, Jianhua Hao and Mi Sun

Mar. Drugs 2017, 15(1), 5; https://doi.org/10.3390/md15010005 - 27 Dec 2016

Cited by 3 | Viewed by 6062

Abstract

Metalloproteases are emerging as useful agents in the treatment of many diseases including arthritis, cancer, cardiovascular diseases, and fibrosis. Studies that could shed light on the metalloprotease pharmaceutical applications require the pure enzyme. Here, we reported the structure-based design and synthesis of the [...] Read more.

Metalloproteases are emerging as useful agents in the treatment of many diseases including arthritis, cancer, cardiovascular diseases, and fibrosis. Studies that could shed light on the metalloprotease pharmaceutical applications require the pure enzyme. Here, we reported the structure-based design and synthesis of the affinity medium for the efficient purification of metalloprotease using the 4-aminophenylboronic acid (4-APBA) as affinity ligand, which was coupled with Sepharose 6B via cyanuric chloride as spacer. The molecular docking analysis showed that the boron atom was interacting with the hydroxyl group of Ser176 residue, whereas the hydroxyl group of the boronic moiety is oriented toward Leu175 and His177 residues. In addition to the covalent bond between the boron atom and hydroxyl group of Ser176, the spacer between boronic acid derivatives and medium beads contributes to the formation of an enzyme-medium complex. With this synthesized medium, we developed and optimized a one-step purification procedure and applied it for the affinity purification of metalloproteases from three commercial enzyme products. The native metalloproteases were purified to high homogeneity with more than 95% purity. The novel purification method developed in this work provides new opportunities for scientific, industrial and pharmaceutical projects. Full article

(This article belongs to the Special Issue Marine Enzymes: Sources, Biochemistry and Bioprocesses for Marine Biotechnology)

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Open AccessArticle

Novel Peptide with Specific Calcium-Binding Capacity from Schizochytrium sp. Protein Hydrolysates and Calcium Bioavailability in Caco-2 Cells

by Xixi Cai, Jiaping Lin and Shaoyun Wang

Mar. Drugs 2017, 15(1), 3; https://doi.org/10.3390/md15010003 - 27 Dec 2016

Cited by 59 | Viewed by 7808

Abstract

Peptide-calcium can probably be a suitable supplement to improve calcium absorption in the human body. In this study, a specific peptide Phe-Tyr (FY) with calcium-binding capacity was purified from Schizochytrium sp. protein hydrolysates through gel filtration chromatography and reversed phase HPLC. The calcium-binding [...] Read more.

Peptide-calcium can probably be a suitable supplement to improve calcium absorption in the human body. In this study, a specific peptide Phe-Tyr (FY) with calcium-binding capacity was purified from Schizochytrium sp. protein hydrolysates through gel filtration chromatography and reversed phase HPLC. The calcium-binding capacity of FY reached 128.77 ± 2.57 μg/mg. Results of ultraviolet spectroscopy, fluorescence spectroscopy, and infrared spectroscopy showed that carboxyl groups, amino groups, and amido groups were the major chelating sites. FY-Ca exhibited excellent thermal stability and solubility, which were beneficial to be absorbed and transported in the basic intestinal tract of the human body. Moreover, the calcium bioavailability in Caco-2 cells showed that FY-Ca could enhance calcium uptake efficiency by more than three times when compared with CaCl₂, and protect calcium ions against dietary inhibitors, such as tannic acid, oxalate, phytate, and Zn²⁺. Our findings further the progress of algae-based peptide-calcium, suggesting that FY-Ca has the potential to be developed as functionally nutraceutical additives. Full article

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

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Open AccessArticle

Pyran Rings Containing Polyketides from Penicillium raistrickii

by Li-Ying Ma, De-Sheng Liu, De-Guo Li, Yu-Ling Huang, Hui-Hui Kang, Chun-Hua Wang and Wei-Zhong Liu

Mar. Drugs 2017, 15(1), 2; https://doi.org/10.3390/md15010002 - 23 Dec 2016

Cited by 17 | Viewed by 7189

Abstract

Five new pyran rings containing polyketides, penicipyrans A–E (1–5), together with the known pestapyrone A (6), were isolated from the saline soil-derived Penicillium raistrickii. Their structures were determined by interpretation of NMR and HRESIMS data. The [...] Read more.

Five new pyran rings containing polyketides, penicipyrans A–E (1–5), together with the known pestapyrone A (6), were isolated from the saline soil-derived Penicillium raistrickii. Their structures were determined by interpretation of NMR and HRESIMS data. The absolute configurations of compounds 4 and 5 were established by the modified Mosher’s method and single-crystal X-ray diffraction analysis, respectively. These compounds possessed high structural diversity including two α-pyrones (1, 2), three isocoumarins (3, 4, 6), and one dihydropyran derivative (5). Among them, Compound 5 exhibited cytotoxicity against HL-60 and K562 cell lines with IC₅₀ values of 4.4 and 8.5 μM, respectively. Full article

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

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Open AccessArticle

Purification and Characterization of a New Alginate Lyase from Marine Bacterium Vibrio sp. SY08

by Shangyong Li, Linna Wang, Jianhua Hao, Mengxin Xing, Jingjing Sun and Mi Sun

Mar. Drugs 2017, 15(1), 1; https://doi.org/10.3390/md15010001 - 23 Dec 2016

Cited by 59 | Viewed by 6995

Abstract

Unsaturated alginate disaccharides (UADs), enzymatically derived from the degradation of alginate polymers, are considered powerful antioxidants. In this study, a new high UAD-producing alginate lyase, AlySY08, has been purified from the marine bacterium Vibrio sp. SY08. AlySY08, with a molecular weight of about [...] Read more.

Unsaturated alginate disaccharides (UADs), enzymatically derived from the degradation of alginate polymers, are considered powerful antioxidants. In this study, a new high UAD-producing alginate lyase, AlySY08, has been purified from the marine bacterium Vibrio sp. SY08. AlySY08, with a molecular weight of about 33 kDa and a specific activity of 1070.2 U/mg, showed the highest activity at 40 °C in phosphate buffer at pH 7.6. The enzyme was stable over a broad pH range (6.0–9.0) and retained about 75% activity after incubation at 40 °C for 2 h. Moreover, the enzyme was active in the absence of salt ions and its activity was enhanced by the addition of NaCl and KCl. AlySY08 resulted in an endo-type alginate lyase that degrades both polyM and polyG blocks, yielding UADs as the main product (81.4% of total products). All these features made AlySY08 a promising candidate for industrial applications in the production of antioxidants from alginate polysaccharides. Full article

(This article belongs to the Collection Marine Polysaccharides)

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Mar. Drugs, Volume 15, Issue 1 (January 2017) – 23 articles

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