Marine Drugs

25 pages, 1032 KiB

Open AccessArticle

Marine and Semi-Synthetic Hydroxysteroids as New Scaffolds for Pregnane X Receptor Modulation

by Valentina Sepe¹, Francesco Saverio Di Leva¹, Claudio D'Amore², Carmen Festa¹, Simona De Marino¹, Barbara Renga², Maria Valeria D'Auria¹, Ettore Novellino¹, Vittorio Limongelli¹, Lisette D'Souza³, Mahesh Majik³, Angela Zampella^1,* and Stefano Fiorucci²

¹ Department of Pharmacy, University of Naples "Federico II", Via D. Montesano, 49, I-80131 Napoli, Italy

² Department Experimental and Clinical Medicine, University of Perugia, Via Gambuli 1, S. Andrea delle Fratte, Perugia 06132, Italy

³ CSIR-National Institute of Oceanography, Dona Paula, Goa 403004, India

Mar. Drugs 2014, 12(6), 3091-3115; https://doi.org/10.3390/md12063091 - 27 May 2014

Cited by 14 | Viewed by 8039

Abstract

In recent years many sterols with unusual structures and promising biological profiles have been identified from marine sources. Here we report the isolation of a series of 24-alkylated-hydroxysteroids from the soft coral Sinularia kavarattiensis, acting as pregnane X receptor (PXR) modulators. Starting [...] Read more.

In recent years many sterols with unusual structures and promising biological profiles have been identified from marine sources. Here we report the isolation of a series of 24-alkylated-hydroxysteroids from the soft coral Sinularia kavarattiensis, acting as pregnane X receptor (PXR) modulators. Starting from this scaffold a number of derivatives were prepared and evaluated for their ability to activate the PXR by assessing transactivation and quantifying gene expression. Our study reveals that ergost-5-en-3β-ol (4) induces PXR transactivation in HepG2 cells and stimulates the expression of the PXR target gene CYP3A4. To shed light on the molecular basis of the interaction between these ligands and PXR, we investigated, through docking simulations, the binding mechanism of the most potent compound of the series, 4, to the PXR. Our findings provide useful functional and structural information to guide further investigations and drug design. Full article

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22 pages, 1547 KiB

Open AccessArticle

Nine New and Five Known Polyketides Derived from a Deep Sea-Sourced Aspergillus sp. 16-02-1

by Xiu-Wen Chen^1,2,3,†, Chang-Wei Li^1,†, Cheng-Bin Cui^1,*, Wei Hua¹, Tian-Jiao Zhu⁴

and Qian-Qun Gu⁴

¹ Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China

² College of Pharmacy, Guangxi Medical University, Nanning 530021, China

³ Department of Biology and Chemistry, Hunan University of Science and Engineering, Yongzhou 425100, China

⁴ Key Laboratory of Marine Drugs, Chinese Ministry of Education, Institute of Marine Drugs and Food, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China

^† These authors contributed equally to this work.

Mar. Drugs 2014, 12(6), 3116-3137; https://doi.org/10.3390/md12063116 - 27 May 2014

Cited by 71 | Viewed by 8459

Abstract

Nine new C₉ polyketides, named aspiketolactonol (1), aspilactonols A–F (2–7), aspyronol (9) and epiaspinonediol (11), were isolated together with five known polyketides, (S)-2-(2′-hydroxyethyl)-4-methyl-γ-butyrolactone (8), dihydroaspyrone (10), [...] Read more.

Nine new C₉ polyketides, named aspiketolactonol (1), aspilactonols A–F (2–7), aspyronol (9) and epiaspinonediol (11), were isolated together with five known polyketides, (S)-2-(2′-hydroxyethyl)-4-methyl-γ-butyrolactone (8), dihydroaspyrone (10), aspinotriol A (12), aspinotriol B (13) and chaetoquadrin F (14), from the secondary metabolites of an Aspergillus sp. 16-02-1 that was isolated from a deep-sea sediment sample. Structures of the new compounds, including their absolute configurations, were determined by spectroscopic methods, especially the 2D NMR, circular dichroism (CD), Mo₂-induced CD and Mosher’s ¹H NMR analyses. Compound 8 was isolated from natural sources for the first time, and the possible biosynthetic pathways for 1–14 were also proposed and discussed. Compounds 1–14 inhibited human cancer cell lines, K562, HL-60, HeLa and BGC-823, to varying extents. Full article

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23 pages, 795 KiB

Open AccessArticle

Investigation of Indolglyoxamide and Indolacetamide Analogues of Polyamines as Antimalarial and Antitrypanosomal Agents

by Jiayi Wang¹, Marcel Kaiser^2,3 and Brent R. Copp^1,*

¹ School of Chemical Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand

² Swiss Tropical and Public Health Institute, Socinstrasse 57, PO Box, Basel CH-4002, Switzerland

³ University of Basel, Basel CH-4003, Switzerland

Mar. Drugs 2014, 12(6), 3138-3160; https://doi.org/10.3390/md12063138 - 28 May 2014

Cited by 19 | Viewed by 6547

Abstract

Pure compound screening has previously identified the indolglyoxy lamidospermidine ascidian metabolites didemnidine A and B (2 and 3) to be weak growth inhibitors of Trypanosoma brucei rhodesiense (IC₅₀ 59 and 44 μM, respectively) and Plasmodium falciparum (K1 dual drug resistant [...] Read more.

Pure compound screening has previously identified the indolglyoxy lamidospermidine ascidian metabolites didemnidine A and B (2 and 3) to be weak growth inhibitors of Trypanosoma brucei rhodesiense (IC₅₀ 59 and 44 μM, respectively) and Plasmodium falciparum (K1 dual drug resistant strain) (IC₅₀ 41 and 15 μM, respectively), but lacking in selectivity (L6 rat myoblast, IC₅₀ 24 μM and 25 μM, respectively). To expand the structure–activity relationship of this compound class towards both parasites, we have prepared and biologically tested a library of analogues that includes indoleglyoxyl and indoleacetic “capping acids”, and polyamines including spermine (PA3-4-3) and extended analogues PA3-8-3 and PA3-12-3. 7-Methoxy substituted indoleglyoxylamides were typically found to exhibit the most potent antimalarial activity (IC₅₀ 10–92 nM) but with varying degrees of selectivity versus the L6 rat myoblast cell line. A 6-methoxyindolglyoxylamide analogue was the most potent growth inhibitor of T. brucei (IC₅₀ 0.18 μM) identified in the study: it, however, also exhibited poor selectivity (L6 IC₅₀ 6.0 μM). There was no apparent correlation between antimalarial and anti-T. brucei activity in the series. In vivo evaluation of one analogue against Plasmodium berghei was undertaken, demonstrating a modest 20.9% reduction in parasitaemia. Full article

(This article belongs to the Special Issue Bioactivity-Focused Syntheses of Marine Natural Products and Congeners)

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29 pages, 3074 KiB

Open AccessReview

Marennine, Promising Blue Pigments from a Widespread Haslea Diatom Species Complex

by Romain Gastineau¹, François Turcotte², Jean-Bernard Pouvreau³

, Michèle Morançais⁴, Joël Fleurence⁴, Eko Windarto¹, Fiddy Semba Prasetiya¹, Sulastri Arsad¹, Pascal Jaouen⁵, Mathieu Babin², Laurence Coiffard⁴

, Céline Couteau⁴, Jean-François Bardeau⁶, Boris Jacquette¹, Vincent Leignel¹, Yann Hardivillier¹, Isabelle Marcotte⁷, Nathalie Bourgougnon⁸, Réjean Tremblay²

, Jean-Sébastien Deschênes², Hope Badawy⁶, Pamela Pasetto⁶, Nikolai Davidovich⁹

, Gert Hansen¹⁰, Jens Dittmer⁶ and Jean-Luc Mouget^1,* Show full author list Hide full author list

¹ FR CNRS 3473 IUML, Mer-Molécules-Santé (MMS), Université du Maine, Ave O. Messiaen, 72085 Le Mans cedex 9, France

² Institut des Sciences de la mer de Rimouski, Université du Québec à Rimouski, 310 des Ursulines, Rimouski, QC G5L 3A1, Canada

³ EA 1157, Laboratoire de Biologie et Pathologie Végétales (LBPV), Université de Nantes, SFR 4207 QUASAV, 44322 Nantes, France

⁴ FR CNRS 3473 IUML, Mer-Molécules-Santé (MMS), Université de Nantes, 44322 Nantes, France

⁵ FR CNRS 3473 IUML, UMR-CNRS 6144 (GEPEA), Université de Nantes, CRTT 37 Bd de l'Université, F-44602 Saint-Nazaire, France

⁶ UMR CNRS 6283, Institut des Molécules et Matériaux du Mans (IMMM), Université du Maine, Ave O. Messiaen, 72085 Le Mans cedex 9, France

⁷ Department of Chemistry, Université du Québec à Montréal, P.O. Box 8888, Downtown Station, Montréal, QC H3C 3P8, Canada

⁸ Université de Bretagne-Sud, Laboratoire de Biotechnologie et Chimie Marines, Campus de Tohannic, F-56017 Vannes, France

⁹ Karadag Nature Reserve of the National Academy of Sciences, p/o Kurortnoe, Feodosiya 98188, Crimea, Ukraine

¹⁰ Department of Biology, Marine Biological Section, University of Copenhagen, Øster Farimagsgade 2D, 1353 Copenhagen, Denmark

Mar. Drugs 2014, 12(6), 3161-3189; https://doi.org/10.3390/md12063161 - 28 May 2014

Cited by 90 | Viewed by 19886

Abstract

In diatoms, the main photosynthetic pigments are chlorophylls a and c, fucoxanthin, diadinoxanthin and diatoxanthin. The marine pennate diatom Haslea ostrearia has long been known for producing, in addition to these generic pigments, a water-soluble blue pigment, marennine. This pigment, responsible for [...] Read more.

In diatoms, the main photosynthetic pigments are chlorophylls a and c, fucoxanthin, diadinoxanthin and diatoxanthin. The marine pennate diatom Haslea ostrearia has long been known for producing, in addition to these generic pigments, a water-soluble blue pigment, marennine. This pigment, responsible for the greening of oysters in western France, presents different biological activities: allelopathic, antioxidant, antibacterial, antiviral, and growth-inhibiting. A method to extract and purify marennine has been developed, but its chemical structure could hitherto not be resolved. For decades, H. ostrearia was the only organism known to produce marennine, and can be found worldwide. Our knowledge about H. ostrearia-like diatom biodiversity has recently been extended with the discovery of several new species of blue diatoms, the recently described H. karadagensis, H. silbo sp. inedit. and H. provincialis sp. inedit. These blue diatoms produce different marennine-like pigments, which belong to the same chemical family and present similar biological activities. Aside from being a potential source of natural blue pigments, H. ostrearia-like diatoms thus present a commercial potential for aquaculture, cosmetics, food and health industries. Full article

(This article belongs to the Special Issue Metabolites in Diatoms)

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13 pages, 1153 KiB

Open AccessArticle

New Prenylxanthones from the Deep-Sea Derived Fungus Emericella sp. SCSIO 05240

by Mangaladoss Fredimoses^†, Xuefeng Zhou^†

, Xiuping Lin, Xinpeng Tian, Wen Ai, Junfeng Wang, Shengrong Liao, Juan Liu, Bin Yang, Xianwen Yang and Yonghong Liu^*

¹ Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China

^† These authors contributed equally to this work.

Mar. Drugs 2014, 12(6), 3190-3202; https://doi.org/10.3390/md12063190 - 28 May 2014

Cited by 47 | Viewed by 7952

Abstract

Four new prenylxanthones, emerixanthones A–D (1–4), together with six known analogues (5–10), were isolated from the culture of the deep-sea sediment derived fungus Emericella sp. SCSIO 05240, which was identified on the basis of morphology [...] Read more.

Four new prenylxanthones, emerixanthones A–D (1–4), together with six known analogues (5–10), were isolated from the culture of the deep-sea sediment derived fungus Emericella sp. SCSIO 05240, which was identified on the basis of morphology and ITS sequence analysis. The newstructures were determined by NMR (¹H, ¹³C NMR, HSQC, HMBC, and ¹H-¹H COSY), MS, CD, and optical rotation analysis. The absolute configuration of prenylxanthone skeleton was also confirmed by the X-ray crystallographic analysis. Compounds 1and 3 showed weak antibacterial activities, and 4 displayed mild antifungal activities against agricultural pathogens. Full article

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15 pages, 1309 KiB

Open AccessArticle

Zn-Driven Discovery of a Hydrothermal Vent Fungal Metabolite Clavatustide C, and an Experimental Study of the Anti-Cancer Mechanism of Clavatustide B

by Panpan Ye¹, Ling Shen¹, Wei Jiang², Ying Ye², Chen-Tung Arthur Chen^2,3, Xiaodan Wu², Kuiwu Wang⁴ and Bin Wu^2,*

¹ Eye Center, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China

² Ocean College, Zhejiang University, Hangzhou 310058, China

³ Institute of Marine Geology and Chemistry, National Sun Yat-sen University, Kaohsiung 80424, Taiwan

⁴ Department of Applied Chemistry, Zhejiang Gongshang University, Hangzhou 310058, China

Mar. Drugs 2014, 12(6), 3203-3217; https://doi.org/10.3390/md12063203 - 28 May 2014

Cited by 37 | Viewed by 7770

Abstract

A naturally new cyclopeptide, clavatustide C, was produced as a stress metabolite in response to abiotic stress elicitation by one of the hydrothermal vent fluid components Zn in the cultured mycelia of Aspergillus clavatus C2WU, which were isolated from Xenograpsus testudinatus. X. [...] Read more.

A naturally new cyclopeptide, clavatustide C, was produced as a stress metabolite in response to abiotic stress elicitation by one of the hydrothermal vent fluid components Zn in the cultured mycelia of Aspergillus clavatus C2WU, which were isolated from Xenograpsus testudinatus. X. testudinatus lives at extreme, toxic habitat around the sulphur-rich hydrothermal vents in Taiwan Kueishantao. The known compound clavatustide B was also isolated and purified. This is the first example of a new hydrothermal vent microbial secondary metabolite produced in response to abiotic Zn treatment. The structures were established by spectroscopic means. The regulation of G1-S transition in hepatocellular carcinoma cell lines by clavatustide B was observed in our previous study. The purpose of the present study was to verify these results in other types of cancer cell lines and elucidate the possible molecular mechanism for the anti-cancer activities of clavatustide B. In different human cancer cell lines, including pancreatic cancer (Panc-1), gastric cancer (MGC-803), colorectal cancer (SW-480), retinoblastoma (WERI-Rb-1) and prostate cancer (PC3), clavatustide B efficiently suppressed cell proliferations in a dose-dependent manner. Although different cancer cell lines presented variety in Max effect dose and IC₅₀ dose, all cancer cell lines showed a lower Max effect dose and IC₅₀ dose compared with human fibroblasts (hFB) (p < 0.05). Moreover, significant accumulations in G1 phases and a reduction in S phases (p < 0.05) were observed under clavatustide B treatment. The expression levels of 2622 genes including 39 cell cycle-associated genes in HepG2 cells were significantly altered by the treatment with 15 μg/mL clavatustide B after 48 h. CCNE2 (cyclin E2) was proved to be the key regulator of clavatustide B-induced G1-S transition blocking in several cancer cell lines by using real-time PCR. Full article

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

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13 pages, 497 KiB

Open AccessArticle

Profiling of Polar Lipids in Marine Oleaginous Diatom Fistulifera solaris JPCC DA0580: Prediction of the Potential Mechanism for Eicosapentaenoic Acid-Incorporation into Triacylglycerol

by Yue Liang¹, Yoshiaki Maeda¹, Tomoko Yoshino¹, Mitsufumi Matsumoto^2,3 and Tsuyoshi Tanaka^1,3,*

¹ Division of Biotechnology and Life Science, Institute of Engineering, Tokyo University of Agriculture and Technology, 2-24-16, Naka-cho, Koganei, Tokyo 184-8588, Japan

² Biotechnology Laboratory, Electric Power Development Co., Ltd., 1, Yanagisaki-machi, Wakamatsu-ku, Kitakyusyu 808-0111, Japan

³ Japan Science and Technology Agency (JST), Core Research for Evolutionary Science and Technology (CREST), 5, Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan

Mar. Drugs 2014, 12(6), 3218-3230; https://doi.org/10.3390/md12063218 - 28 May 2014

Cited by 29 | Viewed by 9015

Abstract

The marine oleaginous diatom Fistulifera solaris JPCC DA0580 is a candidate for biodiesel production because of its high lipid productivity. However, the substantial eicosapentaenoic acid (EPA) content in this strain would affect the biodiesel quality. On the other hand, EPA is also known [...] Read more.

The marine oleaginous diatom Fistulifera solaris JPCC DA0580 is a candidate for biodiesel production because of its high lipid productivity. However, the substantial eicosapentaenoic acid (EPA) content in this strain would affect the biodiesel quality. On the other hand, EPA is also known as the essential health supplement for humans. EPAs are mainly incorporated into glycerolipids in the microalgal cell instead of the presence as free fatty acids. Therefore, the understanding of the EPA biosynthesis including the incorporation of the EPA into glycerolipids especially triacylglycerol (TAG) is fundamental for regulating EPA content for different purposes. In this study, in order to identify the biosynthesis pathway for the EPA-containing TAG species, a lipidomic characterization of the EPA-enriched polar lipids was performed by using direct infusion electrospray ionization (ESI)-Q-TRAP-MS and MS/MS analyses. The determination of the fatty acid positional distribution showed that the sn-2 position of all the chloroplast lipids and part of phosphatidylcholine (PC) species was occupied by C16 fatty acids. This result suggested the critical role of the chloroplast on the lipid synthesis in F. solaris. Furthermore, the exclusive presence of C18 fatty acids in PC highly indicated the biosynthesis of EPA on PC. Finally, the PC-based acyl-editing and head group exchange processes were proposed to be essential for the incorporation of EPA into TAG and chloroplast lipids. Full article

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

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14 pages, 764 KiB

Open AccessArticle

Ilimaquinone and Ethylsmenoquinone, Marine Sponge Metabolites, Suppress the Proliferation of Multiple Myeloma Cells by Down-Regulating the Level of β-Catenin

by Seoyoung Park^1,†, Eunju Yun^2,†, In Hyun Hwang^3,†, Soojin Yoon⁴, Dong-Eun Kim⁴, Ji Seon Kim¹, MinKyun Na^2,*, Gyu-Yong Song^2,* and Sangtaek Oh^1,*

¹ Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul 136-702, Korea

² College of Pharmacy, Chungnam National University, Daejeon 305-764, Korea

³ Department of Chemistry, University of Iowa, Iowa City, IA 52242, USA

⁴ Department of Bioscience and Biotechnology, Konkuk University, Seoul 143-701, Korea

^† These authors contributed equally to this work.

Mar. Drugs 2014, 12(6), 3231-3244; https://doi.org/10.3390/md12063231 - 28 May 2014

Cited by 38 | Viewed by 7068

Abstract

Deregulation of Wnt/β-catenin signaling promotes the development of a broad range of human cancers, including multiple myeloma, and is thus a potential target for the development of therapeutics for this disease. Here, we used a cell-based reporter system to demonstrate that ilimaquinone and [...] Read more.

Deregulation of Wnt/β-catenin signaling promotes the development of a broad range of human cancers, including multiple myeloma, and is thus a potential target for the development of therapeutics for this disease. Here, we used a cell-based reporter system to demonstrate that ilimaquinone and ethylsmenoquinone (formerly smenorthoquinone), sesquiterpene-quinones from a marine sponge, inhibited β-catenin response transcription induced with Wnt3a-conditioned medium, by down-regulating the level of intracellular β-catenin. Pharmacological inhibition of glycogen synthase kinase-3β did not abolish the ilimaquinone and ethylsmenoquinone-mediated β-catenin down-regulation. Degradation of β-catenin was consistently found in RPMI-8226 multiple myeloma cells after ilimaquinone and ethylsmenoquinone treatment. Ilimaquinone and ethylsmenoquinone repressed the expression of cyclin D1, c-myc, and axin-2, which are β-catenin/T-cell factor-dependent genes, and inhibited the proliferation of multiple myeloma cells. In addition, ilimaquinone and ethylsmenoquinone significantly induced G₀/G₁ cell cycle arrest and apoptosis in RPMI-8266 cells. These findings suggest that ilimaquinone and ethylsmenoquinone exert their anti-cancer activity by blocking the Wnt/β-catenin pathway and have significant potential as therapies for multiple myeloma. Full article

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38 pages, 1790 KiB

Open AccessReview

Quorum Quenching Agents: Resources for Antivirulence Therapy

by Kaihao Tang and Xiao-Hua Zhang^*

College of Marine Life Sciences, Ocean University of China, Qingdao 266003, China

Mar. Drugs 2014, 12(6), 3245-3282; https://doi.org/10.3390/md12063245 - 30 May 2014

Cited by 137 | Viewed by 19896

Abstract

The continuing emergence of antibiotic-resistant pathogens is a concern to human health and highlights the urgent need for the development of alternative therapeutic strategies. Quorum sensing (QS) regulates virulence in many bacterial pathogens, and thus, is a promising target for antivirulence therapy which [...] Read more.

The continuing emergence of antibiotic-resistant pathogens is a concern to human health and highlights the urgent need for the development of alternative therapeutic strategies. Quorum sensing (QS) regulates virulence in many bacterial pathogens, and thus, is a promising target for antivirulence therapy which may inhibit virulence instead of cell growth and division. This means that there is little selective pressure for the evolution of resistance. Many natural quorum quenching (QQ) agents have been identified. Moreover, it has been shown that many microorganisms are capable of producing small molecular QS inhibitors and/or macromolecular QQ enzymes, which could be regarded as a strategy for bacteria to gain benefits in competitive environments. More than 30 species of marine QQ bacteria have been identified thus far, but only a few of them have been intensively studied. Recent studies indicate that an enormous number of QQ microorganisms are undiscovered in the highly diverse marine environments, and these marine microorganism-derived QQ agents may be valuable resources for antivirulence therapy. Full article

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

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9 pages, 614 KiB

Open AccessArticle

Violapyrones H and I, New Cytotoxic Compounds Isolated from Streptomyces sp. Associated with the Marine Starfish Acanthaster planci

by Hee Jae Shin^1,2,*, Hwa-Sun Lee¹, Jong Seok Lee¹, Junho Shin¹, Min Ah Lee¹, Hyi-Seung Lee¹, Yeon-Ju Lee¹

, Jieun Yun³ and Jong Soon Kang³

¹ Marine Natural Products Chemistry Laboratory, Korea Institute of Ocean Science and Technology, 787 Haeanro, Ansan 426-744, Korea

² Department of Marine Biotechnology, University of Science and Technology, 217 Gajungro, Daejeon 305-350, Korea

³ Bio-Evaluation Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanjiro, Cheongwon 323-883, Korea

Mar. Drugs 2014, 12(6), 3283-3291; https://doi.org/10.3390/md12063283 - 30 May 2014

Cited by 34 | Viewed by 8143

Abstract

Two new α-pyrone derivatives, violapyrones H (1) and I (2), along with known violapyrones B (3) and C (4) were isolated from the fermentation broth of a marine actinomycete Streptomyces sp. The strain was derived [...] Read more.

Two new α-pyrone derivatives, violapyrones H (1) and I (2), along with known violapyrones B (3) and C (4) were isolated from the fermentation broth of a marine actinomycete Streptomyces sp. The strain was derived from a crown-of-thorns starfish, Acanthaster planci, collected from Chuuk, Federated States of Micronesia. The structures of violapyrones were elucidated by the analysis of 1D and 2D NMR and HR-ESIMS data. Violapyrones (1–4) exhibited cytotoxicity against 10 human cancer cell lines with GI₅₀ values of 1.10–26.12 μg/mL when tested using sulforhodamine B (SRB) assay. This is the first report on the cytotoxicity of violapyrones against cancer cell lines and the absolute configuration of violapyrone C. Full article

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

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15 pages, 1555 KiB

Open AccessArticle

The Protective Effect of Fucoidan in Rats with Streptozotocin-Induced Diabetic Nephropathy

by Jing Wang^1,3,4, Huaide Liu², Ning Li^1,*, Quanbin Zhang^1,3,4 and Hong Zhang¹

¹ Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China

² School of Life Sciences, Nantong University, Seyuan Road 9, Nantong 226019, China

³ Nantong Branch, Institute of Oceanology, Chinese Academy of Sciences, Nantong, Jiangsu 226006, China

⁴ Collaborative Innovation Center for Marine Biomass Fibers, Materials and Textiles of Shandong Province, Qingdao 266071, China

Mar. Drugs 2014, 12(6), 3292-3306; https://doi.org/10.3390/md12063292 - 30 May 2014

Cited by 76 | Viewed by 9270

Abstract

Diabetic nephropathy (DN) has long been recognized as the leading cause of end-stage renal disease, but the efficacy of available strategies for the prevention of DN remains poor. The aim of this study was to investigate the possible beneficial effects of fucoidan (FPS) [...] Read more.

Diabetic nephropathy (DN) has long been recognized as the leading cause of end-stage renal disease, but the efficacy of available strategies for the prevention of DN remains poor. The aim of this study was to investigate the possible beneficial effects of fucoidan (FPS) in streptozotocin (STZ)-induced diabetes in rats. Wistar rats were made diabetic by injection of STZ after removal of the right kidney. FPS was administered to these diabetic rats for 10 weeks. Body weight, physical activity, renal function, and renal morphometry were measured after 10 weeks of treatment. In the FPS-treated group, the levels of blood glucose, BUN, Ccr and Ucr decreased significantly, and microalbumin, serum insulin and the β2-MG content increased significantly. Moreover, the FPS-treated group showed improvements in renal morphometry. In summary, FPS can ameliorate the metabolic abnormalities of diabetic rats and delay the progression of diabetic renal complications. Full article

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

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16 pages, 1485 KiB

Open AccessArticle

Identification of Marine Neuroactive Molecules in Behaviour-Based Screens in the Larval Zebrafish

by Si-Mei Long^1,†, Feng-Yin Liang^1,†, Qi Wu¹, Xi-Lin Lu¹, Xiao-Li Yao¹, Shi-Chang Li², Jing Li², Huanxing Su³, Ji-Yan Pang^2,* and Zhong Pei^1,*

¹ Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China

² School of Chemistry & Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, China

³ State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China

^† These authors contributed equally to this work.

Mar. Drugs 2014, 12(6), 3307-3322; https://doi.org/10.3390/md12063307 - 30 May 2014

Cited by 18 | Viewed by 9871

Abstract

High-throughput behavior-based screen in zebrafish is a powerful approach for the discovery of novel neuroactive small molecules for treatment of nervous system diseases such as epilepsy. To identify neuroactive small molecules, we first screened 36 compounds (1–36) derived from [...] Read more.

High-throughput behavior-based screen in zebrafish is a powerful approach for the discovery of novel neuroactive small molecules for treatment of nervous system diseases such as epilepsy. To identify neuroactive small molecules, we first screened 36 compounds (1–36) derived from marine natural products xyloketals and marine isoprenyl phenyl ether obtained from the mangrove fungus. Compound 1 demonstrated the most potent inhibition on the locomotor activity in larval zebrafish. Compounds 37–42 were further synthesized and their potential anti-epilepsy action was then examined in a PTZ-induced epilepsy model in zebrafish. Compound 1 and compounds 39, 40 and 41 could significantly attenuate PTZ-induced locomotor hyperactivity and elevation of c-fos mRNA in larval zebrafish. Compound 40 showed the most potent inhibitory action against PTZ-induced hyperactivity. The structure-activity analysis showed that the OH group at 12-position played a critical role and the substituents at the 13-position were well tolerated in the inhibitory activity of xyloketal derivatives. Thus, these derivatives may provide some novel drug candidates for the treatment of epilepsy. Full article

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

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29 pages, 831 KiB

Open AccessArticle

Metabolomic Profiling and Genomic Study of a Marine Sponge-Associated Streptomyces sp.

by Christina Viegelmann^1,†, Lekha Menon Margassery^2,†

, Jonathan Kennedy^2,*, Tong Zhang¹, Ciarán O'Brien², Fergal O'Gara^2,3,4,5

, John P. Morrissey^2,3, Alan D. W. Dobson^2,3

and RuAngelie Edrada-Ebel^1,*

¹ Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, The John Arbuthnott Building, 161 Cathedral Street, Glasgow, Scotland G4 0RE, UK

² Marine Biotechnology Centre, Environmental Research Institute, University College Cork, Lee Road, Cork, Ireland

³ School of Microbiology, University College Cork, Cork, Ireland

⁴ Biomerit Research Centre, University College Cork, Cork, Ireland

⁵ School of Biomedical Sciences, Curtin University, Perth 6102, WA, Australia

^† These authors contributed equally to this work.

Mar. Drugs 2014, 12(6), 3323-3351; https://doi.org/10.3390/md12063323 - 2 Jun 2014

Cited by 49 | Viewed by 12287

Abstract

Metabolomics and genomics are two complementary platforms for analyzing an organism as they provide information on the phenotype and genotype, respectively. These two techniques were applied in the dereplication and identification of bioactive compounds from a Streptomyces sp. (SM8) isolated from the sponge [...] Read more.

Metabolomics and genomics are two complementary platforms for analyzing an organism as they provide information on the phenotype and genotype, respectively. These two techniques were applied in the dereplication and identification of bioactive compounds from a Streptomyces sp. (SM8) isolated from the sponge Haliclona simulans from Irish waters. Streptomyces strain SM8 extracts showed antibacterial and antifungal activity. NMR analysis of the active fractions proved that hydroxylated saturated fatty acids were the major components present in the antibacterial fractions. Antimycin compounds were initially putatively identified in the antifungal fractions using LC-Orbitrap. Their presence was later confirmed by comparison to a standard. Genomic analysis of Streptomyces sp. SM8 revealed the presence of multiple secondary metabolism gene clusters, including a gene cluster for the biosynthesis of the antifungal antimycin family of compounds. The antimycin gene cluster of Streptomyces sp. SM8 was inactivated by disruption of the antimycin biosynthesis gene antC. Extracts from this mutant strain showed loss of antimycin production and significantly less antifungal activity than the wild-type strain. Three butenolides, 4,10-dihydroxy-10-methyl-dodec-2-en-1,4-olide (1), 4,11-dihydroxy-10-methyl-dodec-2-en-1,4-olide (2), and 4-hydroxy-10-methyl-11-oxo-dodec-2-en-1,4-olide (3) that had previously been reported from marine Streptomyces species were also isolated from SM8. Comparison of the extracts of Streptomyces strain SM8 and its host sponge, H. simulans, using LC-Orbitrap revealed the presence of metabolites common to both extracts, providing direct evidence linking sponge metabolites to a specific microbial symbiont. Full article

(This article belongs to the Special Issue Metabolomics - Applications in Marine Natural Products Chemistry)

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19 pages, 791 KiB

Open AccessArticle

First Total Syntheses and Antimicrobial Evaluation of Penicimonoterpene, a Marine-Derived Monoterpenoid, and Its Various Derivatives

by Jian-Chun Zhao^1,2

, Xiao-Ming Li¹, James B. Gloer³ and Bin-Gui Wang^1,*

¹ Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Nanhai Road 7, Qingdao 266071, China

² University of Chinese Academy of Sciences, Yuquan Road 19A, Beijing 100049, China

³ Department of Chemistry, University of Iowa, Iowa City, IA 52242, USA

Mar. Drugs 2014, 12(6), 3352-3370; https://doi.org/10.3390/md12063352 - 3 Jun 2014

Cited by 11 | Viewed by 6802

Abstract

The first total synthesis of marine-derived penicimonoterpene (±)-1 has been achieved in four steps from 6-methylhept-5-en-2-one using a Reformatsky reaction as the key step to construct the basic carbon skeleton. A total of 24 new derivatives of 1 have also been designed [...] Read more.

The first total synthesis of marine-derived penicimonoterpene (±)-1 has been achieved in four steps from 6-methylhept-5-en-2-one using a Reformatsky reaction as the key step to construct the basic carbon skeleton. A total of 24 new derivatives of 1 have also been designed and synthesized. Their structures were characterized by analysis of their ¹H NMR, ¹³C NMR and HRESIMS data. Some of them showed significant antibacterial activity against Aeromonas hydrophila, Escherichia coli, Micrococcus luteus, Staphylococcus aureus, Vibrio anguillarum, V. harveyi and/or V. parahaemolyticus, and some showed activity against plant-pathogenic fungi (Alternaria brassicae, Colletotrichum gloeosporioides and/or Fusarium graminearum). Some of the derivatives exhibited antimicrobial MIC values ranging from 0.25 to 4 μg/mL, which were stronger than those of the positive control. Notably, Compounds 3b and 10 showed extremely high selectively against plant-pathogenic fungus F. graminearum (MIC 0.25 μg/mL) and pathogenic bacteria E. coli (MIC 1 μg/mL), implying their potential as antimicrobial agents. SAR analysis of 1 and its derivatives indicated that modification of the carbon-carbon double bond at C-6/7, of groups on the allylic methylene unit and of the carbonyl group at C-1, effectively enhanced the antimicrobial activity. Full article

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10 pages, 798 KiB

Open AccessArticle

Numerosol A–D, New Cembranoid Diterpenes from the Soft Coral Sinularia numerosa

by Yen-Ju Tseng¹, Yuan-Chien Yang¹, Shang-Kwei Wang^2,3,* and Chang-Yih Duh^1,3,4,*

¹ Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 804, Taiwan

² Department of Microbiology, Kaohsiung Medical University, Kaohsiung 807, Taiwan

³ Asia-Pacific Ocean Research Center, National Sun Yat-sen University, Kaohsiung 804, Taiwan

⁴ Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807, Taiwan

Mar. Drugs 2014, 12(6), 3371-3380; https://doi.org/10.3390/md12063371 - 3 Jun 2014

Cited by 14 | Viewed by 5744

Abstract

Four new cembrane-type diterpenes; numerosol A–D (1–4); along with a known steroid; gibberoketosterol (5); were isolated from the Taiwanese soft coral Sinularia numerosa. The structures of these metabolites were determined by extensive analysis of spectroscopic data. [...] Read more.

Four new cembrane-type diterpenes; numerosol A–D (1–4); along with a known steroid; gibberoketosterol (5); were isolated from the Taiwanese soft coral Sinularia numerosa. The structures of these metabolites were determined by extensive analysis of spectroscopic data. Gibberoketosterol (5) exhibited cytotoxicity against P-388 (mouse lymphocytic leukemia) cell line with an ED₅₀ of 6.9 μM. Full article

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18 pages, 1247 KiB

Open AccessArticle

Effects of Long Chain Fatty Acid Synthesis and Associated Gene Expression in Microalga Tetraselmis sp.

by T. Catalina Adarme-Vega, Skye R. Thomas-Hall, David K. Y. Lim and Peer M. Schenk^*

Algae Biotechnology Laboratory, School of Agriculture and Food Sciences, The University of Queensland, Brisbane, Queensland 4072, Australia

Mar. Drugs 2014, 12(6), 3381-3398; https://doi.org/10.3390/md12063381 - 4 Jun 2014

Cited by 59 | Viewed by 9381

Abstract

With the depletion of global fish stocks, caused by high demand and effective fishing techniques, alternative sources for long chain omega-3 fatty acids are required for human nutrition and aquaculture feeds. Recent research has focused on land-based cultivation of microalgae, the primary producers [...] Read more.

With the depletion of global fish stocks, caused by high demand and effective fishing techniques, alternative sources for long chain omega-3 fatty acids are required for human nutrition and aquaculture feeds. Recent research has focused on land-based cultivation of microalgae, the primary producers of omega-3 fatty acids in the marine food web. The effect of salinity on fatty acids and related gene expression was studied in the model marine microalga, Tetraselmis sp. M8. Correlations were found for specific fatty acid biosynthesis and gene expression according to salinity and the growth phase. Low salinity was found to increase the conversion of C18:4 stearidonic acid (SDA) to C20:4 eicosatetraenoic acid (ETA), correlating with increased transcript abundance of the Δ-6-elongase-encoding gene in salinities of 5 and 10 ppt compared to higher salinity levels. The expression of the gene encoding β-ketoacyl-coenzyme was also found to increase at lower salinities during the nutrient deprivation phase (Day 4), but decreased with further nutrient stress. Nutrient deprivation also triggered fatty acids synthesis at all salinities, and C20:5 eicosapentaenoic acid (EPA) increased relative to total fatty acids, with nutrient starvation achieving a maximum of 7% EPA at Day 6 at a salinity of 40 ppt. Full article

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17 pages, 893 KiB

Open AccessArticle

Potent Cytotoxic Peptides from the Australian Marine Sponge Pipestela candelabra

by Trong D. Tran, Ngoc B. Pham, Gregory A. Fechner, John N. A. Hooper

and Ronald J. Quinn^*

Eskitis Institute for Drug Discovery, Griffith University, Brisbane, Queensland 4111, Australia

Mar. Drugs 2014, 12(6), 3399-3415; https://doi.org/10.3390/md12063399 - 4 Jun 2014

Cited by 22 | Viewed by 7744

Abstract

Two consecutive prefractionated fractions of the Australian marine sponge extract, Pipestela candelabra, were identified to be selectively active on the human prostate cancer cells (PC3) compared to the human neonatal foreskin fibroblast non-cancer cells (NFF). Twelve secondary metabolites were isolated in which [...] Read more.

Two consecutive prefractionated fractions of the Australian marine sponge extract, Pipestela candelabra, were identified to be selectively active on the human prostate cancer cells (PC3) compared to the human neonatal foreskin fibroblast non-cancer cells (NFF). Twelve secondary metabolites were isolated in which four compounds are new small peptides. Their structures were characterized by spectroscopic and chemical analysis. These compounds inhibited selectively the growth of prostate cancer cells with IC₅₀ values in the picomolar to sub-micromolar range. Structure-activity relationship of these compounds is discussed. Full article

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33 pages, 1484 KiB

Open AccessArticle

Metabolomic Tools for Secondary Metabolite Discovery from Marine Microbial Symbionts

by Lynsey Macintyre^1,*, Tong Zhang¹, Christina Viegelmann¹, Ignacio Juarez Martinez¹, Cheng Cheng^1,2, Catherine Dowdells¹, Usama Ramadan Abdelmohsen²

, Christine Gernert², Ute Hentschel² and RuAngelie Edrada-Ebel^1,*

¹ Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK

² Department of Botany II, Julius-von-Sachs Institute for Biological Sciences, University of Würzburg, Julius-von-Sachs-Platz 3, D-97082 Würzburg, Germany

Mar. Drugs 2014, 12(6), 3416-3448; https://doi.org/10.3390/md12063416 - 5 Jun 2014

Cited by 122 | Viewed by 16486

Abstract

Marine invertebrate-associated symbiotic bacteria produce a plethora of novel secondary metabolites which may be structurally unique with interesting pharmacological properties. Selection of strains usually relies on literature searching, genetic screening and bioactivity results, often without considering the chemical novelty and abundance of secondary [...] Read more.

Marine invertebrate-associated symbiotic bacteria produce a plethora of novel secondary metabolites which may be structurally unique with interesting pharmacological properties. Selection of strains usually relies on literature searching, genetic screening and bioactivity results, often without considering the chemical novelty and abundance of secondary metabolites being produced by the microorganism until the time-consuming bioassay-guided isolation stages. To fast track the selection process, metabolomic tools were used to aid strain selection by investigating differences in the chemical profiles of 77 bacterial extracts isolated from cold water marine invertebrates from Orkney, Scotland using liquid chromatography-high resolution mass spectrometry (LC-HRMS) and nuclear magnetic resonance (NMR) spectroscopy. Following mass spectrometric analysis and dereplication using an Excel macro developed in-house, principal component analysis (PCA) was employed to differentiate the bacterial strains based on their chemical profiles. NMR ¹H and correlation spectroscopy (COSY) were also employed to obtain a chemical fingerprint of each bacterial strain and to confirm the presence of functional groups and spin systems. These results were then combined with taxonomic identification and bioassay screening data to identify three bacterial strains, namely Bacillus sp. 4117, Rhodococcus sp. ZS402 and Vibrio splendidus strain LGP32, to prioritize for scale-up based on their chemically interesting secondary metabolomes, established through dereplication and interesting bioactivities, determined from bioassay screening. Full article

(This article belongs to the Special Issue Metabolomics - Applications in Marine Natural Products Chemistry)

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17 pages, 2064 KiB

Open AccessArticle

Characterization of a Novel Conus bandanus Conopeptide Belonging to the M-Superfamily Containing Bromotryptophan

by Bao Nguyen^1,2, Jean-Pierre Le Caer³, Gilles Mourier⁴, Robert Thai⁴, Hung Lamthanh^1,2, Denis Servent⁴

, Evelyne Benoit¹ and Jordi Molgó^1,*

¹ Neurobiology and Development Laboratory, Research Unit # 3294, Institute of Neurobiology Alfred Fessard # 2118, National Center for Scientific Research, Gif sur Yvette Cedex 91198, France

² Institute of Biotechnology and Environment, University of Nha Trang, Nha Trang, Khanh Hoa 57000, Vietnam

³ Research Unit # 2301, Natural Product Chemistry Institute, National Center for Scientific Research, Gif sur Yvette Cedex 91198, France

⁴ Molecular Engineering of Proteins, Institute of Biology and Technology Saclay, Atomic Energy Commission, Gif sur Yvette Cedex 91191, France

Mar. Drugs 2014, 12(6), 3449-3465; https://doi.org/10.3390/md12063449 - 5 Jun 2014

Cited by 13 | Viewed by 7498

Abstract

A novel conotoxin (conopeptide) was biochemically characterized from the crude venom of the molluscivorous marine snail, Conus bandanus (Hwass in Bruguière, 1792), collected in the south-central coast of Vietnam. The peptide was identified by screening bromotryptophan from chromatographic fractions of the crude venom. [...] Read more.

A novel conotoxin (conopeptide) was biochemically characterized from the crude venom of the molluscivorous marine snail, Conus bandanus (Hwass in Bruguière, 1792), collected in the south-central coast of Vietnam. The peptide was identified by screening bromotryptophan from chromatographic fractions of the crude venom. Tandem mass spectrometry techniques were used to detect and localize different post-translational modifications (PTMs) present in the BnIIID conopeptide. The sequence was confirmed by Edman’s degradation and mass spectrometry revealing that the purified BnIIID conopeptide had 15 amino acid residues, with six cysteines at positions 1, 2, 7, 11, 13, and 14, and three PTMs: bromotryptophan, γ-carboxy glutamate, and amidated aspartic acid, at positions “4”, “5”, and “15”, respectively. The BnIIID peptide was synthesized for comparison with the native peptide. Homology comparison with conopeptides having the III-cysteine framework (–CCx₁x₂x₃x₄Cx₁x₂x₃Cx₁CC–) revealed that BnIIID belongs to the M-1 family of conotoxins. This is the first report of a member of the M-superfamily containing bromotryptophan as PTM. Full article

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

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11 pages, 430 KiB

Open AccessArticle

Chromomycins A₂ and A₃ from Marine Actinomycetes with TRAIL Resistance-Overcoming and Wnt Signal Inhibitory Activities

by Kazufumi Toume, Kentaro Tsukahara, Hanako Ito, Midori A. Arai and Masami Ishibashi^*

Department of Natural Products Chemistry, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan

Mar. Drugs 2014, 12(6), 3466-3476; https://doi.org/10.3390/md12063466 - 5 Jun 2014

Cited by 25 | Viewed by 7248

Abstract

A biological screening study of an actinomycetes strain assembly was conducted using a cell-based cytotoxicity assay. The CKK1019 strain was isolated from a sea sand sample. Cytotoxicity-guided fractionation of the CKK1019 strain culture broth, which exhibited cytotoxicity, led to the isolation of chromomycins [...] Read more.

A biological screening study of an actinomycetes strain assembly was conducted using a cell-based cytotoxicity assay. The CKK1019 strain was isolated from a sea sand sample. Cytotoxicity-guided fractionation of the CKK1019 strain culture broth, which exhibited cytotoxicity, led to the isolation of chromomycins A₂ (1) and A₃ (2). 1 and 2 showed potent cytotoxicity against the human gastric adenocarcinoma (AGS) cell line (IC₅₀ 1; 1.7 and 2; 22.1 nM), as well as strong inhibitory effects against TCF/β-catenin transcription (IC₅₀ 1; 1.8 and 2; 15.9 nM). 2 showed the ability to overcome tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) resistance. To the best of our knowledge, the effects of chromomycins A₂ (1) and A₃ (2) on TRAIL resistance-overcoming activity, and on the Wnt signaling pathway, have not been reported previously. Thus, 1 and 2 warrant potential drug lead studies in relation to TRAIL-resistant and Wnt signal-related diseases and offer potentially useful chemical probes for investigating TRAIL resistance and the Wnt signaling pathway. Full article

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

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10 pages, 807 KiB

Open AccessCommunication

Cespitulones A and B, Cytotoxic Diterpenoids of a New Structure Class from the Soft Coral Cespitularia taeniata

by Yu-Chi Lin^1,2, Shih-Sheng Wang³, Chung-Hsiung Chen¹, Yao-Haur Kuo⁴ and Ya-Ching Shen^1,*

¹ School of Pharmacy, College of Medicine, National Taiwan University, Taipei 100, Taiwan

² Department of Life Sciences, National Cheng Kung University, No. 1 University Road, Tainan 701, Taiwan

³ Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung 804, Taiwan

⁴ Division of Herbal Drugs and Natural Products, National Research Institute of Chinese Medicine, Taipei 112, Taiwan

Mar. Drugs 2014, 12(6), 3477-3486; https://doi.org/10.3390/md12063477 - 5 Jun 2014

Cited by 6 | Viewed by 5751

Abstract

Two novel diterpenoids, cespitulones A (1) and B (2), were isolated from extracts of the soft coral Cespitularia taeniata. Both compounds possess an unprecedented bicyclo [10.3.1] ring system with C-C bond connections between C-10 and C-20, and between [...] Read more.

Two novel diterpenoids, cespitulones A (1) and B (2), were isolated from extracts of the soft coral Cespitularia taeniata. Both compounds possess an unprecedented bicyclo [10.3.1] ring system with C-C bond connections between C-10 and C-20, and between C-20 and C-11. Their structures were elucidated on the basis of extensive spectroscopic analyses. Compound 1 exhibited significant cytotoxicity against human medulloblastoma and colon adenocarcinoma cancer cells. Full article

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29 pages, 1030 KiB

Open AccessReview

Chlorella zofingiensis as an Alternative Microalgal Producer of Astaxanthin: Biology and Industrial Potential

by Jin Liu^1,2,*, Zheng Sun³

, Henri Gerken⁴, Zheng Liu⁵, Yue Jiang⁶ and Feng Chen^1,*

¹ Institute for Food & Bioresource Engineering, College of Engineering, Peking University, Beijing 100871, China

² Institute of Marine and Environmental Technology, University of Maryland Center for Environmental Science, Baltimore, MD 21202, USA

³ College of Fisheries and Life Science, Shanghai Ocean University, Shanghai 201306, China

⁴ Department of Applied Sciences and Mathematics, Arizona State University Polytechnic campus, Mesa, AZ 85212, USA

⁵ Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA

⁶ School of Food Science, Jiangnan University, Wuxi 214122, China

Mar. Drugs 2014, 12(6), 3487-3515; https://doi.org/10.3390/md12063487 - 10 Jun 2014

Cited by 275 | Viewed by 21588

Abstract

Astaxanthin (3,3′-dihydroxy-β,β-carotene-4,4′-dione), a high-value ketocarotenoid with a broad range of applications in food, feed, nutraceutical, and pharmaceutical industries, has been gaining great attention from science and the public in recent years. The green microalgae Haematococcus pluvialis and Chlorella zofingiensis represent the most promising [...] Read more.

Astaxanthin (3,3′-dihydroxy-β,β-carotene-4,4′-dione), a high-value ketocarotenoid with a broad range of applications in food, feed, nutraceutical, and pharmaceutical industries, has been gaining great attention from science and the public in recent years. The green microalgae Haematococcus pluvialis and Chlorella zofingiensis represent the most promising producers of natural astaxanthin. Although H. pluvialis possesses the highest intracellular astaxanthin content and is now believed to be a good producer of astaxanthin, it has intrinsic shortcomings such as slow growth rate, low biomass yield, and a high light requirement. In contrast, C. zofingiensis grows fast phototrophically, heterotrophically and mixtrophically, is easy to be cultured and scaled up both indoors and outdoors, and can achieve ultrahigh cell densities. These robust biotechnological traits provide C. zofingiensis with high potential to be a better organism than H. pluvialis for mass astaxanthin production. This review aims to provide an overview of the biology and industrial potential of C. zofingiensis as an alternative astaxanthin producer. The path forward for further expansion of the astaxanthin production from C. zofingiensis with respect to both challenges and opportunities is also discussed. Full article

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44 pages, 1657 KiB

Open AccessReview

Emerging Strategies and Integrated Systems Microbiology Technologies for Biodiscovery of Marine Bioactive Compounds

by Javier Rocha-Martin¹, Catriona Harrington¹, Alan D.W. Dobson^2,3

and Fergal O'Gara^1,2,3,4,*

¹ BIOMERIT Research Centre, School of Microbiology, University College Cork, National University of Ireland, Cork, Ireland

² School of Microbiology, University College Cork, National University of Ireland, Cork, Ireland

³ Marine Biotechnology Centre, Environmental Research Institute, University College Cork, National University of Ireland, Cork, Ireland

⁴ School of Biomedical Sciences, Curtin University, Perth, WA 6102, Australia

Mar. Drugs 2014, 12(6), 3516-3559; https://doi.org/10.3390/md12063516 - 10 Jun 2014

Cited by 66 | Viewed by 17060

Abstract

Marine microorganisms continue to be a source of structurally and biologically novel compounds with potential use in the biotechnology industry. The unique physiochemical properties of the marine environment (such as pH, pressure, temperature, osmolarity) and uncommon functional groups (such as isonitrile, dichloroimine, isocyanate, [...] Read more.

Marine microorganisms continue to be a source of structurally and biologically novel compounds with potential use in the biotechnology industry. The unique physiochemical properties of the marine environment (such as pH, pressure, temperature, osmolarity) and uncommon functional groups (such as isonitrile, dichloroimine, isocyanate, and halogenated functional groups) are frequently found in marine metabolites. These facts have resulted in the production of bioactive substances with different properties than those found in terrestrial habitats. In fact, the marine environment contains a relatively untapped reservoir of bioactivity. Recent advances in genomics, metagenomics, proteomics, combinatorial biosynthesis, synthetic biology, screening methods, expression systems, bioinformatics, and the ever increasing availability of sequenced genomes provides us with more opportunities than ever in the discovery of novel bioactive compounds and biocatalysts. The combination of these advanced techniques with traditional techniques, together with the use of dereplication strategies to eliminate known compounds, provides a powerful tool in the discovery of novel marine bioactive compounds. This review outlines and discusses the emerging strategies for the biodiscovery of these bioactive compounds. Full article

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

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14 pages, 561 KiB

Open AccessArticle

Acetylcholinesterase Inhibitory Activity of Pigment Echinochrome A from Sea Urchin Scaphechinus mirabilis

by Sung Ryul Lee^1,2, Julius Ryan D. Pronto^1,2, Bolor-Erdene Sarankhuu^1,2, Kyung Soo Ko^1,2, Byoung Doo Rhee^1,2, Nari Kim^1,2, Natalia P. Mishchenko³

, Sergey A. Fedoreyev³, Valentin A. Stonik³ and Jin Han^1,2,*

¹ National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan 614-735, Korea

² Department of Health Sciences and Technology, Graduate School of Inje University, Busan 613-735, Korea

³ Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, Prospect 100 let Vladivostoku, 159, Vladivostok 690022, Russia

Mar. Drugs 2014, 12(6), 3560-3573; https://doi.org/10.3390/md12063560 - 10 Jun 2014

Cited by 36 | Viewed by 8297

Abstract

Echinochrome A (EchA) is a dark-red pigment of the polyhydroxynaphthoquinone class isolated from sea urchin Scaphechinus mirabilis. Acetylcholinesterase (AChE) inhibitors are used in the treatment of various neuromuscular disorders, and are considered as strong therapeutic agents for the treatment of Alzheimer’s disease [...] Read more.

Echinochrome A (EchA) is a dark-red pigment of the polyhydroxynaphthoquinone class isolated from sea urchin Scaphechinus mirabilis. Acetylcholinesterase (AChE) inhibitors are used in the treatment of various neuromuscular disorders, and are considered as strong therapeutic agents for the treatment of Alzheimer’s disease (AD). Although EchA is clinically used to treat ophthalmic diseases and limit infarct formation during ischemia/ reperfusion injury, anti-AChE effect of EchA is still unknown. In this study, we investigated the anti-AChE effect of EchA in vitro. EchA and its exhausted form which lost anti-oxidant capacity did not show any significant cytotoxicy on the H9c2 and A7r5 cells. EchA inhibited AChE with an irreversible and uncompetitive mode. In addition, EchA showed reactive oxygen species scavenging activity, particularly with nitric oxide. These findings indicate new therapeutic potential for EchA in treating reduced acetylcholine-related diseases including AD and provide an insight into developing new AChE inhibitors. Full article

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13 pages, 856 KiB

Open AccessArticle

Diazaquinomycins E–G, Novel Diaza-Anthracene Analogs from a Marine-Derived Streptomyces sp.

by Michael W. Mullowney¹, Eoghainín Ó hAinmhire^1,2, Anam Shaikh¹, Xiaomei Wei^1,2, Urszula Tanouye^1,2, Bernard D. Santarsiero^1,2, Joanna E. Burdette^1,2 and Brian T. Murphy^1,2,*

¹ Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, IL 60612, USA

² Center for Pharmaceutical Biotechnology, University of Illinois at Chicago, Chicago, IL 60607, USA

Mar. Drugs 2014, 12(6), 3574-3586; https://doi.org/10.3390/md12063574 - 11 Jun 2014

Cited by 19 | Viewed by 8051

Abstract

As part of our program to identify novel secondary metabolites that target drug-resistant ovarian cancers, a screening of our aquatic-derived actinomycete fraction library against a cisplatin-resistant ovarian cancer cell line (OVCAR5) led to the isolation of novel diaza-anthracene antibiotic diazaquinomycin E (DAQE; 1 [...] Read more.

As part of our program to identify novel secondary metabolites that target drug-resistant ovarian cancers, a screening of our aquatic-derived actinomycete fraction library against a cisplatin-resistant ovarian cancer cell line (OVCAR5) led to the isolation of novel diaza-anthracene antibiotic diazaquinomycin E (DAQE; 1), the isomeric mixture of diazaquinomycin F (DAQF; 2) and diazaquinomycin G (DAQG; 3), and known analog diazaquinomycin A (DAQA; 4). The structures of DAQF and DAQG were solved through deconvolution of X-Ray diffraction data of their corresponding co-crystal. DAQE and DAQA exhibited moderate LC₅₀ values against OVCAR5 of 9.0 and 8.8 μM, respectively. At lethal concentrations of DAQA, evidence of DNA damage was observed via induction of apoptosis through cleaved-PARP. Herein, we will discuss the isolation, structure elucidation, and biological activity of these secondary metabolites. Full article

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21 pages, 660 KiB

Open AccessArticle

Link between Domoic Acid Production and Cell Physiology after Exchange of Bacterial Communities between Toxic Pseudo-nitzschia multiseries and Non-Toxic Pseudo-nitzschia delicatissima

by Aurélie Lelong, Hélène Hégaret^* and Philippe Soudant

Marine Environmental Sciences Laboratory (Laboratoire des sciences de l'environnement marin, LEMAR), UMR6539, European Institute for Marine Studies (Institut Universitaire Européen de la Mer, IUEM), Rue Dumont d'Urville, Plouzané 29280, France

Mar. Drugs 2014, 12(6), 3587-3607; https://doi.org/10.3390/md12063587 - 11 Jun 2014

Cited by 15 | Viewed by 7711

Abstract

Bacteria are known to influence domoic acid (DA) production by Pseudo-nitzschia spp., but the link between DA production and physiology of diatoms requires more investigation. We compared a toxic P. multiseries to a non-toxic P. delicatissima, investigating links between DA production, physiological [...] Read more.

Bacteria are known to influence domoic acid (DA) production by Pseudo-nitzschia spp., but the link between DA production and physiology of diatoms requires more investigation. We compared a toxic P. multiseries to a non-toxic P. delicatissima, investigating links between DA production, physiological parameters, and co-occurring bacteria. Bacterial communities in cultures of both species were reduced by antibiotic treatment, and each of the diatoms was inoculated with the bacterial community of the other species. The physiology of P. delicatissima was minimally affected by the absence of bacteria or the presence of alien bacteria, and no DA was detected. P. multiseries grew faster without bacteria, did not produce a significant amount of DA, and exhibited physiological characteristics of healthy cells. When grown with alien bacteria, P. multiseries did not grow and produced more DA; the physiology of these cells was affected, with decreases in chlorophyll content and photosynthetic efficiency, an increase in esterase activity, and almost 50% mortality of the cells. The alien bacterial community had morphological and cellular characteristics very different from the original bacteria, and the number of free-living bacteria per algal cell was much higher, suggesting the involvement of bacteria in DA production. Full article

(This article belongs to the Special Issue Metabolites in Diatoms)

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26 pages, 2024 KiB

Open AccessReview

Quinone and Hydroquinone Metabolites from the Ascidians of the Genus Aplidium

by Camila Spereta Bertanha, Ana Helena Januário, Tavane Aparecida Alvarenga, Letícia Pereira Pimenta, Márcio Luis Andrade e Silva, Wilson Roberto Cunha and Patrícia Mendonça Pauletti^*

Center for Research in Exact and Technological Sciences, University of Franca, Avenue Doutor Armando Salles Oliveira, 201, Franca, São Paulo 14404-600, Brazil

Mar. Drugs 2014, 12(6), 3608-3633; https://doi.org/10.3390/md12063608 - 12 Jun 2014

Cited by 24 | Viewed by 10239

Abstract

Ascidians of the genus Aplidium are recognized as an important source of chemical diversity and bioactive natural products. Among the compounds produced by this genus are non-nitrogenous metabolites, mainly prenylated quinones and hydroquinones. This review discusses the isolation, structural elucidation, and biological activities [...] Read more.

Ascidians of the genus Aplidium are recognized as an important source of chemical diversity and bioactive natural products. Among the compounds produced by this genus are non-nitrogenous metabolites, mainly prenylated quinones and hydroquinones. This review discusses the isolation, structural elucidation, and biological activities of quinones, hydroquinones, rossinones, longithorones, longithorols, floresolides, scabellones, conicaquinones, aplidinones, thiaplidiaquinones, and conithiaquinones. A compilation of the ¹³C-NMR spectral data of these compounds is also presented. Full article

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

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26 pages, 3632 KiB

Open AccessReview

Total Synthesis and Structure-Activity Relationship of Glycoglycerolipids from Marine Organisms

by Jun Zhang, Chunxia Li^*

, Guangli Yu

and Huashi Guan

Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China

Mar. Drugs 2014, 12(6), 3634-3659; https://doi.org/10.3390/md12063634 - 18 Jun 2014

Cited by 45 | Viewed by 10558

Abstract

Glycoglycerolipids occur widely in natural products, especially in the marine species. Glycoglycerolipids have been shown to possess a variety of bioactivities. This paper will review the different methodologies and strategies for the synthesis of biological glycoglycerolipids and their analogs for bioactivity assay. In [...] Read more.

Glycoglycerolipids occur widely in natural products, especially in the marine species. Glycoglycerolipids have been shown to possess a variety of bioactivities. This paper will review the different methodologies and strategies for the synthesis of biological glycoglycerolipids and their analogs for bioactivity assay. In addition, the bioactivities and structure-activity relationship of the glycoglycerolipids are also briefly outlined. Full article

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9 pages, 168 KiB

Open AccessReview

Siphonaxanthin, a Green Algal Carotenoid, as a Novel Functional Compound

by Tatsuya Sugawara^1,*, Ponesakki Ganesan^1,2, Zhuosi Li¹, Yuki Manabe¹ and Takashi Hirata^1,3

¹ Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kitashirakawaoiwakecho, Sakyo-ku, Kyoto 606-8502, Japan

² SRM Research Institute, SRM University, Kattankulathur, Tamilnadu 603 203, India

³ Department of Rehabilitation, Shijonawate Gakuen University, 5-11-10 Hojo, Daito, Osaka 574-0011, Japan

Mar. Drugs 2014, 12(6), 3660-3668; https://doi.org/10.3390/md12063660 - 19 Jun 2014

Cited by 79 | Viewed by 9922

Abstract

Siphonaxanthin is a specific keto-carotenoid in green algae whose bio-functional properties are yet to be identified. This review focuses on siphonaxanthin as a bioactive compound and outlines the evidence associated with functionality. Siphonaxanthin has been reported to potently inhibit the viability of human [...] Read more.

Siphonaxanthin is a specific keto-carotenoid in green algae whose bio-functional properties are yet to be identified. This review focuses on siphonaxanthin as a bioactive compound and outlines the evidence associated with functionality. Siphonaxanthin has been reported to potently inhibit the viability of human leukemia HL-60 cells via induction of apoptosis. In comparison with fucoxanthin, siphonaxanthin markedly reduced cell viability as early as 6 h after treatment. The cellular uptake of siphonaxanthin was 2-fold higher than fucoxanthin. It has been proposed that siphonaxanthin possesses significant anti-angiogenic activity in studies using human umbilical vein endothelial cells and rat aortic ring. The results of these studies suggested that the anti-angiogenic effect of siphonaxanthin is due to the down-regulation of signal transduction by fibroblast growth factor receptor-1 in vascular endothelial cells. Siphonaxanthin also exhibited inhibitory effects on antigen-induced degranulation of mast cells. These findings open up new avenues for future research on siphonaxanthin as a bioactive compound, and additional investigation, especially in vivo studies, are required to validate these findings. In addition, further studies are needed to determine its bioavailability and metabolic fate. Full article

(This article belongs to the Special Issue Marine Carotenoids (Special Issue))

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12 pages, 864 KiB

Open AccessArticle

Eurothiocin A and B, Sulfur-Containing Benzofurans from a Soft Coral-Derived Fungus Eurotium rubrum SH-823

by Zhaoming Liu, Guoping Xia, Senhua Chen, Yayue Liu, Hanxiang Li^* and Zhigang She^*

School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, China

Mar. Drugs 2014, 12(6), 3669-3680; https://doi.org/10.3390/md12063669 - 20 Jun 2014

Cited by 52 | Viewed by 8993

Abstract

Two new sulfur-containing benzofuran derivatives, eurothiocin A and B (1 and 2), along with five known compounds, zinniol (3), butyrolactone I (4), aspernolide D (5), vermistatin (6), and methoxyvermistatin (7), were [...] Read more.

Two new sulfur-containing benzofuran derivatives, eurothiocin A and B (1 and 2), along with five known compounds, zinniol (3), butyrolactone I (4), aspernolide D (5), vermistatin (6), and methoxyvermistatin (7), were isolated from the cultures of Eurotium rubrum SH-823, a fungus obtained from a Sarcophyton sp. soft coral collected from the South China Sea. The new compounds (1 and 2) share a methyl thiolester moiety, which is quite rare among natural secondary metabolites. The structures of these metabolites were assigned on the basis of detailed spectroscopic analysis. The absolute configurations of 1 and 2 were determined by comparison of the experimental and calculated electronic circular dichroism (ECD) data. Compounds 1 and 2 exhibited more potent inhibitory effects against α-glucosidase activity than the clinical α-glucosidase inhibitor acarbose. Further mechanistic analysis showed that both of them exhibited competitive inhibition characteristics. Full article

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

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25 pages, 693 KiB

Open AccessArticle

Accurate Dereplication of Bioactive Secondary Metabolites from Marine-Derived Fungi by UHPLC-DAD-QTOFMS and a MS/HRMS Library

by Sara Kildgaard, Maria Mansson, Ina Dosen, Andreas Klitgaard, Jens C. Frisvad

, Thomas O. Larsen and Kristian F. Nielsen^*

Department of Systems Biology, Technical University of Denmark, Soeltofts Plads 221, Kgs. Lyngby DK-2800, Denmark

Mar. Drugs 2014, 12(6), 3681-3705; https://doi.org/10.3390/md12063681 - 20 Jun 2014

Cited by 122 | Viewed by 14796

Abstract

In drug discovery, reliable and fast dereplication of known compounds is essential for identification of novel bioactive compounds. Here, we show an integrated approach using ultra-high performance liquid chromatography-diode array detection-quadrupole time of flight mass spectrometry (UHPLC-DAD-QTOFMS) providing both accurate mass full-scan mass [...] Read more.

In drug discovery, reliable and fast dereplication of known compounds is essential for identification of novel bioactive compounds. Here, we show an integrated approach using ultra-high performance liquid chromatography-diode array detection-quadrupole time of flight mass spectrometry (UHPLC-DAD-QTOFMS) providing both accurate mass full-scan mass spectrometry (MS) and tandem high resolution MS (MS/HRMS) data. The methodology was demonstrated on compounds from bioactive marine-derived strains of Aspergillus, Penicillium, and Emericellopsis, including small polyketides, non-ribosomal peptides, terpenes, and meroterpenoids. The MS/HRMS data were then searched against an in-house MS/HRMS library of ~1300 compounds for unambiguous identification. The full scan MS data was used for dereplication of compounds not in the MS/HRMS library, combined with ultraviolet/visual (UV/Vis) and MS/HRMS data for faster exclusion of database search results. This led to the identification of four novel isomers of the known anticancer compound, asperphenamate. Except for very low intensity peaks, no false negatives were found using the MS/HRMS approach, which proved to be robust against poor data quality caused by system overload or loss of lock-mass. Only for small polyketides, like patulin, were both retention time and UV/Vis spectra necessary for unambiguous identification. For the ophiobolin family with many structurally similar analogues partly co-eluting, the peaks could be assigned correctly by combining MS/HRMS data and m/z of the [M + Na]⁺ ions. Full article

(This article belongs to the Special Issue Metabolomics - Applications in Marine Natural Products Chemistry)

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27 pages, 1011 KiB

Open AccessArticle

Confirmation of Pinnatoxins and Spirolides in Shellfish and Passive Samplers from Catalonia (Spain) by Liquid Chromatography Coupled with Triple Quadrupole and High-Resolution Hybrid Tandem Mass Spectrometry

by María García-Altares¹, Alexis Casanova¹, Vaishali Bane², Jorge Diogène¹, Ambrose Furey² and Pablo De la Iglesia^1,*

¹ Institute of Agrifood Research and Technology (IRTA), Poble Nou Road, km. 5.5, Sant Carles de la Ràpita 43540, Spain

² Mass Spectrometry Research Centre (MSRC) and PROTEOBIO Research Group, Department of Chemistry, Cork Institute of Technology, Bishopstown, Cork, Ireland

Mar. Drugs 2014, 12(6), 3706-3732; https://doi.org/10.3390/md12063706 - 23 Jun 2014

Cited by 74 | Viewed by 7848

Abstract

Cyclic imines are lipophilic marine toxins that bioaccumulate in seafood. Their structure comprises a cyclic-imino moiety, responsible for acute neurotoxicity in mice. Cyclic imines have not been linked yet to human poisonings and are not regulated in Europe, although the European Food Safety [...] Read more.

Cyclic imines are lipophilic marine toxins that bioaccumulate in seafood. Their structure comprises a cyclic-imino moiety, responsible for acute neurotoxicity in mice. Cyclic imines have not been linked yet to human poisonings and are not regulated in Europe, although the European Food Safety Authority requires more data to perform a conclusive risk assessment for consumers. This work presents the first detection of pinnatoxin G (PnTX-G) in Spain and 13-desmethyl spirolide C (SPX-1) in shellfish from Catalonia (Spain, NW Mediterranean Sea). Cyclic imines were found at low concentrations (2 to 60 µg/kg) in 13 samples of mussels and oysters (22 samples analyzed). Pinnatoxin G has been also detected in 17 seawater samples (out of 34) using solid phase adsorption toxin tracking devices (0.3 to 0.9 µg/kg-resin). Pinnatoxin G and SPX-1 were confirmed with both low and high resolution (<2 ppm) mass spectrometry by comparison of the response with that from reference standards. For other analogs without reference standards, we applied a strategy combining low resolution MS with a triple quadrupole mass analyzer for a fast and reliable screening, and high resolution MS LTQ Orbitrap^® for unambiguous confirmation. The advantages and limitations of using high resolution MS without reference standards were discussed. Full article

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

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21 pages, 736 KiB

Open AccessArticle

Analysis of the Biomass Composition of the Demosponge Amphimedon queenslandica on Heron Island Reef, Australia

by Jabin R. Watson¹, Timothy C. R. Brennan², Bernard M. Degnan¹, Sandie M. Degnan¹ and Jens O. Krömer^3,*

¹ School of Biological Science, University of Queensland, Brisbane, Queensland 4072, Australia

² Systems and Synthetic Biology Group, Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Queensland 4072, Australia

³ Centre for Microbial Electrosynthesis (CEMES), Advanced Water Management Centre, University of Queensland, Brisbane, Queensland 4072, Australia

Mar. Drugs 2014, 12(6), 3733-3753; https://doi.org/10.3390/md12063733 - 23 Jun 2014

Cited by 6 | Viewed by 6584

Abstract

Marine sponges are a potential source of important pharmaceutical drugs, the commercialisation of which is restricted by the difficulties of obtaining a sufficient and regular supply of biomass. One way to optimize commercial cell lines for production is the in-depth characterization and target [...] Read more.

Marine sponges are a potential source of important pharmaceutical drugs, the commercialisation of which is restricted by the difficulties of obtaining a sufficient and regular supply of biomass. One way to optimize commercial cell lines for production is the in-depth characterization and target identification through genome scale metabolic modeling and flux analysis. By applying these tools to a sponge, we hope to gain insights into how biomass is formed. We chose Amphimedon queenslandica as it has an assembled and annotated genome, a prerequisite for genome scale modeling. The first stepping stone on the way to metabolic flux analysis in a sponge holobiont, is the characterization of its biomass composition. In this study we quantified the macromolecular composition and investigated the variation between and within sponges of a single population. We found lipids and protein to be the most abundant macromolecules, while carbohydrates were the most variable. We also analysed the composition and abundance of the fatty acids and amino acids, the important building blocks required to synthesise the abundant macromolecule types, lipids, and protein. These data complement the extensive genomic information available for A. queenslandica and lay the basis for genome scale modelling and flux analysis. Full article

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

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16 pages, 696 KiB

Open AccessArticle

Amino Alcohols from the Ascidian Pseudodistoma sp.

by Tae Hyung Won¹, Minjung You¹, So-Hyoung Lee², Boon Jo Rho³, Dong-Chan Oh^1,*, Ki-Bong Oh² and Jongheon Shin^1,*

¹ Natural Products Research Institute, College of Pharmacy, Seoul National University, San 56-1, Sillim, Gwanak, Seoul 151-742, Korea

² Department of Agricultural Biotechnology, College of Agriculture and Life Science, Seoul National University, San 56-1, Sillim, Gwanak, Seoul 151-921, Korea

³ Department of Biological Science, College of Life Science, Ewha Womans University, 52, Ewhayeodae-gil, Seodaemun, Seoul 120-750, Korea

Mar. Drugs 2014, 12(6), 3754-3769; https://doi.org/10.3390/md12063754 - 24 Jun 2014

Cited by 14 | Viewed by 6358

Abstract

Seven new amino alcohol compounds, pseudoaminols A–G (1–7), were isolated from the ascidian Pseudodistoma sp. collected off the coast of Chuja-do, Korea. Structures of these new compounds were determined by analysis of the spectroscopic data and from chemical conversion. [...] Read more.

Seven new amino alcohol compounds, pseudoaminols A–G (1–7), were isolated from the ascidian Pseudodistoma sp. collected off the coast of Chuja-do, Korea. Structures of these new compounds were determined by analysis of the spectroscopic data and from chemical conversion. The presence of an N-carboxymethyl group in two of the new compounds (6 and 7) is unprecedented among amino alcohols. Several of these compounds exhibited moderate antimicrobial activity and cytotoxicity, as well as weak inhibitory activity toward Na⁺/K⁺-ATPase. Full article

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Mar. Drugs, Volume 12, Issue 6 (June 2014) – 35 articles , Pages 3091-3791

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