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Mar. Drugs, Volume 8, Issue 10 (October 2010) – 12 articles , Pages 2546-2732

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Research

Jump to: Review

912 KiB  
Article
Metabolomic Investigations of American Oysters Using 1H-NMR Spectroscopy
by Andrey P. Tikunov, Christopher B. Johnson, Haakil Lee, Michael K. Stoskopf and Jeffrey M. Macdonald
Mar. Drugs 2010, 8(10), 2578-2596; https://doi.org/10.3390/md8102578 - 08 Oct 2010
Cited by 62 | Viewed by 10696
Abstract
The Eastern oyster (Crassostrea virginica) is a useful, robust model marine organism for tissue metabolism studies. Its relatively few organs are easily delineated and there is sufficient understanding of their functions based on classical assays to support interpretation of advanced spectroscopic [...] Read more.
The Eastern oyster (Crassostrea virginica) is a useful, robust model marine organism for tissue metabolism studies. Its relatively few organs are easily delineated and there is sufficient understanding of their functions based on classical assays to support interpretation of advanced spectroscopic approaches. Here we apply high-resolution proton nuclear magnetic resonance (1H NMR)-based metabolomic analysis to C. virginica to investigate the differences in the metabolic profile of different organ groups, and magnetic resonance imaging (MRI) to non-invasively identify the well separated organs. Metabolites were identified in perchloric acid extracts of three portions of the oyster containing: (1) adductor muscle, (2) stomach and digestive gland, and (3) mantle and gills. Osmolytes dominated the metabolome in all three organ blocks with decreasing concentration as follows: betaine > taurine > proline > glycine > ß-alanine > hypotaurine. Mitochondrial metabolism appeared most pronounced in the adductor muscle with elevated levels of carnitine facilitating ß-oxidation, and ATP, and phosphoarginine synthesis, while glycogen was elevated in the mantle/gills and stomach/digestive gland. A biochemical schematic is presented that relates metabolites to biochemical pathways correlated with physiological organ functions. This study identifies metabolites and corresponding 1H NMR peak assignments for future NMR-based metabolomic studies in oysters. Full article
(This article belongs to the Special Issue Metabolomic Approaches to Marine Organisms)
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327 KiB  
Article
Effect of Marine Polyunsaturated Fatty Acids on Biofilm Formation of Candida albicans and Candida dubliniensis
by Vuyisile S. Thibane, Johan L. F. Kock, Ruan Ells, Pieter W. J. van Wyk and Carolina H. Pohl
Mar. Drugs 2010, 8(10), 2597-2604; https://doi.org/10.3390/md8102597 - 08 Oct 2010
Cited by 49 | Viewed by 14220
Abstract
The effect of marine polyunsaturated fatty acids on biofilm formation by the human pathogens Candida albicans and Candida dubliniensis was investigated. It was found that stearidonic acid (18:4 n-3), eicosapentaenoic acid (20:5 n-3), docosapentaenoic acid (22:5 n-3) and docosahexaenoic acid (22:6 n-3) have [...] Read more.
The effect of marine polyunsaturated fatty acids on biofilm formation by the human pathogens Candida albicans and Candida dubliniensis was investigated. It was found that stearidonic acid (18:4 n-3), eicosapentaenoic acid (20:5 n-3), docosapentaenoic acid (22:5 n-3) and docosahexaenoic acid (22:6 n-3) have an inhibitory effect on mitochondrial metabolism of both C. albicans and C. dubliniensis and that the production of biofilm biomass by C. dubliniensis was more susceptible to these fatty acids than C. albicans. Ultrastructural differences, which may be due to increased oxidative stress, were observed between treated and untreated cells of C. albicans and C. dubliniensis with formation of rough cell walls by both species and fibrillar structures in C. dubliniensis. These results indicate that marine polyunsaturated fatty acids may be useful in the treatment and/or prevention of biofilms formed by these pathogenic yeasts. Full article
(This article belongs to the Special Issue Marine Lipids)
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281 KiB  
Article
Characterization and Online Detection of Surfactin Isomers Based on HPLC-MSn Analyses and Their Inhibitory Effects on the Overproduction of Nitric Oxide and the Release of TNF-α and IL-6 in LPS-Induced Macrophages
by Jin-Shan Tang, Feng Zhao, Hao Gao, Yi Dai, Zhi-Hong Yao, Kui Hong, Jia Li, Wen-Cai Ye and Xin-Sheng Yao
Mar. Drugs 2010, 8(10), 2605-2618; https://doi.org/10.3390/md8102605 - 11 Oct 2010
Cited by 56 | Viewed by 11452
Abstract
A rapid method for characterization and online detection of surfactin isomers was developed based on HPLC-MSn (n = 1, 2, 3) analyses, and many surfactin isomers were detected and characterized from the bioactive fraction of the mangrove bacterium Bacillus sp. Inhibitory activities [...] Read more.
A rapid method for characterization and online detection of surfactin isomers was developed based on HPLC-MSn (n = 1, 2, 3) analyses, and many surfactin isomers were detected and characterized from the bioactive fraction of the mangrove bacterium Bacillus sp. Inhibitory activities of surfactin isomers on the overproduction of nitric oxide and the release of TNF-a and IL-6 in LPS-induced macrophages were systematically investigated. It was revealed that the surfactin isomers showed strong inhibitory properties on the overproduction of nitric oxide and the release of IL-6 on LPS-induced murine macrophage cell RAW264.7 with IC50 values ranging from 1.0 to 7.0 mM. Structure-activity relationship (SAR) studies revealed that the existence of the free carboxyl group in the structure of surfactin isomers was crucial. These findings will be very helpful for the development of this novel kind of natural product as new anti-inflammatory agents. Full article
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174 KiB  
Article
Excavatoids O and P, New 12-Hydroxybriaranes from the Octocoral Briareum excavatum
by Ping-Jyun Sung, Gung-Ying Li, Yin-Di Su, Mei-Ru Lin, Yu-Chia Chang, Ting-Hsuan Kung, Chan-Shing Lin, Yung-Husan Chen, Jui-Hsin Su, Mei-Chin Lu, Jimmy Kuo, Ching-Feng Weng and Tsong-Long Hwang
Mar. Drugs 2010, 8(10), 2639-2646; https://doi.org/10.3390/md8102639 - 12 Oct 2010
Cited by 16 | Viewed by 9558
Abstract
Two new 12-hydroxybriarane diterpenoids, designated as excavatoids O (1) and P (2), were isolated from the octocoral Briareum excavatum. The structures of briaranes 1 and 2 were established on the basis of extensive spectral data analysis. Excavatoid P [...] Read more.
Two new 12-hydroxybriarane diterpenoids, designated as excavatoids O (1) and P (2), were isolated from the octocoral Briareum excavatum. The structures of briaranes 1 and 2 were established on the basis of extensive spectral data analysis. Excavatoid P (2) is the first metabolite which possesses a 6b-chlorine atom in briarane analogues. Full article
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118 KiB  
Article
Trabectedin for Metastatic Soft Tissue Sarcoma: A Retrospective Single Center Analysis
by Thomas Schmitt, Eva Keller, Sascha Dietrich, Patrick Wuchter, Anthony D. Ho and Gerlinde Egerer
Mar. Drugs 2010, 8(10), 2647-2658; https://doi.org/10.3390/md8102647 - 13 Oct 2010
Cited by 11 | Viewed by 10522
Abstract
Soft tissue sarcoma (STS) comprises a large variety of rare malignant tumors. Development of distant metastasis is frequent, even in patients undergoing initial curative surgery. Trabectedin, a tetrahydroisoquinoline alkaloid isolated from the Caribbean marine tunicate Ecteinascidia turbinata, was approved in 2007 for [...] Read more.
Soft tissue sarcoma (STS) comprises a large variety of rare malignant tumors. Development of distant metastasis is frequent, even in patients undergoing initial curative surgery. Trabectedin, a tetrahydroisoquinoline alkaloid isolated from the Caribbean marine tunicate Ecteinascidia turbinata, was approved in 2007 for patients with advanced STS after failure of anthracyclines and ifosfamide, or for patients unsuited to receive these agents. In this study, we retrospectively analyzed 25 patients who had been treated with trabectedin at our institution between 2007 and 2010. The majority (72%) had been heavily pre-treated with ³2 previous lines of chemotherapy. Response assessed by conventional RECIST criteria was low, with only one patient achieving a partial remission (PR) and 10 stable disease (SD) after three cycles of treatment. However, median progression-free survival (PFS) and overall survival (OS) were significantly prolonged in this population compared to non-responders, with 7.7 months versus 2.1 months (p < 0.0001; HR 15.37, 95% CI 4.3 to 54.5) and 12.13 months versus 5.54 months (p = 0.0137; HR 3.7, 95% CI 1.3 to 10.5), respectively. PFS for all patients was 58% at three months and 37% at six months. Side effects, including neutropenia, elevation of liver transaminases/liver function tests, and nausea/vomiting, were usually mild and manageable. However, dose reductions due to side effects were necessary in five patients. We conclude that trabectedin is an effective and generally well tolerated treatment for STS even in a heavily pre-treated patient population. Full article
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307 KiB  
Article
Marine Benthic Cyanobacteria Contain Apoptosis-Inducing Activity Synergizing with Daunorubicin to Kill Leukemia Cells, but not Cardiomyocytes
by Linn Oftedal, Frode Selheim, Matti Wahlsten, Kaarina Sivonen, Stein Ove Døskeland and Lars Herfindal
Mar. Drugs 2010, 8(10), 2659-2672; https://doi.org/10.3390/md8102659 - 14 Oct 2010
Cited by 49 | Viewed by 9315
Abstract
The potential of marine benthic cyanobacteria as a source of anticancer drug candidates was assessed in a screen for induction of cell death (apoptosis) in acute myeloid leukemia (AML) cells. Of the 41 marine cyanobacterial strains screened, more than half contained cell death-inducing [...] Read more.
The potential of marine benthic cyanobacteria as a source of anticancer drug candidates was assessed in a screen for induction of cell death (apoptosis) in acute myeloid leukemia (AML) cells. Of the 41 marine cyanobacterial strains screened, more than half contained cell death-inducing activity. Several strains contained activity against AML cells, but not against non-malignant cells like hepatocytes and cardiomyoblasts. The apoptotic cell death induced by the various strains could be distinguished by the role of caspase activation and sensitivity to the recently detected chemotherapy-resistance-associated prosurvival protein LEDGF/p75. One strain (M44) was particularly promising since its activity counteracted the protective effect of LEDGF/p75 overexpressed in AML cells, acted synergistically with the anthracycline anticancer drug daunorubicin in AML cells, and protected cardiomyoblasts against the toxic effect of anthracyclines. We conclude that culturable benthic marine cyanobacteria from temperate environments provide a promising and hitherto underexploited source for novel antileukemic drugs. Full article
(This article belongs to the Special Issue Marine Drugs as Antitumour Agents)
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404 KiB  
Article
Toxic Effects of Domoic Acid in the Seabream Sparus aurata
by Isabel Nogueira, Alexandre Lobo-da-Cunha, António Afonso, Socorro Rivera, Joana Azevedo, Rogério Monteiro, Rosa Cervantes, Ana Gago-Martinez and Vítor Vasconcelos
Mar. Drugs 2010, 8(10), 2721-2732; https://doi.org/10.3390/md8102721 - 15 Oct 2010
Cited by 15 | Viewed by 9709
Abstract
Neurotoxicity induced in fish by domoic acid (DA) was assessed with respect to occurrence of neurotoxic signs, lethality, and histopathology by light microscopy. Sparus aurata were exposed to a single dose of DA by intraperitoneal (i.p.) injection of 0, 0.45, 0.9, and 9.0 [...] Read more.
Neurotoxicity induced in fish by domoic acid (DA) was assessed with respect to occurrence of neurotoxic signs, lethality, and histopathology by light microscopy. Sparus aurata were exposed to a single dose of DA by intraperitoneal (i.p.) injection of 0, 0.45, 0.9, and 9.0 mg DA kg−1 bw. Mortality (66.67 ± 16.67%) was only observed in dose of 9.0 mg kg−1 bw. Signs of neurological toxicity were detected for the doses of 0.9 and 9.0 mg DA kg−1 bw. Furthermore, the mean concentrations (±SD) of DA detected by HPLC-UV in extracts of brain after exposure to 9.0 mg DA kg−1 bw were 0.61 ± 0.01, 0.96 ± 0.00, and 0.36 ± 0.01 mg DA kg−1 tissue at 1, 2, and 4 hours. The lack of major permanent brain damage in S. aurata, and reversibility of neurotoxic signs, suggest that lower susceptibility to DA or neuronal recovery occurs in affected individuals. Full article
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Review

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367 KiB  
Review
Symbiodinium—Invertebrate Symbioses and the Role of Metabolomics
by Benjamin R. Gordon and William Leggat
Mar. Drugs 2010, 8(10), 2546-2568; https://doi.org/10.3390/md8102546 - 30 Sep 2010
Cited by 93 | Viewed by 17059
Abstract
Symbioses play an important role within the marine environment. Among the most well known of these symbioses is that between coral and the photosynthetic dinoflagellate, Symbiodinium spp. Understanding the metabolic relationships between the host and the symbiont is of the utmost importance in [...] Read more.
Symbioses play an important role within the marine environment. Among the most well known of these symbioses is that between coral and the photosynthetic dinoflagellate, Symbiodinium spp. Understanding the metabolic relationships between the host and the symbiont is of the utmost importance in order to gain insight into how this symbiosis may be disrupted due to environmental stressors. Here we summarize the metabolites related to nutritional roles, diel cycles and the common metabolites associated with the invertebrate-Symbiodinium relationship. We also review the more obscure metabolites and toxins that have been identified through natural products and biomarker research. Finally, we discuss the key role that metabolomics and functional genomics will play in understanding these important symbioses. Full article
(This article belongs to the Special Issue Metabolomic Approaches to Marine Organisms)
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113 KiB  
Review
Demospongic Acids Revisited
by Jean-Michel Kornprobst and Gilles Barnathan
Mar. Drugs 2010, 8(10), 2569-2577; https://doi.org/10.3390/md8102569 - 08 Oct 2010
Cited by 37 | Viewed by 8882
Abstract
The well-known fatty acids with a D5,9 unsaturation system were designated for a long period as demospongic acids, taking into account that they originally occurred in marine Demospongia sponges. However, such acids have also been observed in various marine sources with a large [...] Read more.
The well-known fatty acids with a D5,9 unsaturation system were designated for a long period as demospongic acids, taking into account that they originally occurred in marine Demospongia sponges. However, such acids have also been observed in various marine sources with a large range of chain-lengths (C16–C32) and from some terrestrial plants with short acyl chains (C18–C19). Finally, the D5,9 fatty acids appear to be a particular type of non-methylene-interrupted fatty acids (NMA FAs). This article reviews the occurrence of these particular fatty acids in marine and terrestrial organisms and shows the biosynthetic connections between D5,9 fatty acids and other NMI FAs. Full article
(This article belongs to the Special Issue Marine Lipids)
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388 KiB  
Review
Antiviral Lead Compounds from Marine Sponges
by Sunil Sagar, Mandeep Kaur and Kenneth P. Minneman
Mar. Drugs 2010, 8(10), 2619-2638; https://doi.org/10.3390/md8102619 - 11 Oct 2010
Cited by 194 | Viewed by 20130
Abstract
Marine sponges are currently one of the richest sources of pharmacologically active compounds found in the marine environment. These bioactive molecules are often secondary metabolites, whose main function is to enable and/or modulate cellular communication and defense. They are usually produced by functional [...] Read more.
Marine sponges are currently one of the richest sources of pharmacologically active compounds found in the marine environment. These bioactive molecules are often secondary metabolites, whose main function is to enable and/or modulate cellular communication and defense. They are usually produced by functional enzyme clusters in sponges and/or their associated symbiotic microorganisms. Natural product lead compounds from sponges have often been found to be promising pharmaceutical agents. Several of them have successfully been approved as antiviral agents for clinical use or have been advanced to the late stages of clinical trials. Most of these drugs are used for the treatment of human immunodeficiency virus (HIV) and herpes simplex virus (HSV). The most important antiviral lead of marine origin reported thus far is nucleoside Ara-A (vidarabine) isolated from sponge Tethya crypta. It inhibits viral DNA polymerase and DNA synthesis of herpes, vaccinica and varicella zoster viruses. However due to the discovery of new types of viruses and emergence of drug resistant strains, it is necessary to develop new antiviral lead compounds continuously. Several sponge derived antiviral lead compounds which are hopedto be developed as future drugs are discussed in this review. Supply problems are usually the major bottleneck to the development of these compounds as drugs during clinical trials. However advances in the field of metagenomics and high throughput microbial cultivation has raised the possibility that these techniques could lead to the cost-effective large scale production of such compounds. Perspectives on biotechnological methods with respect to marine drug development are also discussed. Full article
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499 KiB  
Review
Immense Essence of Excellence: Marine Microbial Bioactive Compounds
by Ira Bhatnagar and Se-Kwon Kim
Mar. Drugs 2010, 8(10), 2673-2701; https://doi.org/10.3390/md8102673 - 15 Oct 2010
Cited by 308 | Viewed by 27998
Abstract
Oceans have borne most of the biological activities on our planet. A number of biologically active compounds with varying degrees of action, such as anti-tumor, anti-cancer, anti-microtubule, anti-proliferative, cytotoxic, photo protective, as well as antibiotic and antifouling properties, have been isolated to date [...] Read more.
Oceans have borne most of the biological activities on our planet. A number of biologically active compounds with varying degrees of action, such as anti-tumor, anti-cancer, anti-microtubule, anti-proliferative, cytotoxic, photo protective, as well as antibiotic and antifouling properties, have been isolated to date from marine sources. The marine environment also represents a largely unexplored source for isolation of new microbes (bacteria, fungi, actinomycetes, microalgae-cyanobacteria and diatoms) that are potent producers of bioactive secondary metabolites. Extensive research has been done to unveil the bioactive potential of marine microbes (free living and symbiotic) and the results are amazingly diverse and productive. Some of these bioactive secondary metabolites of microbial origin with strong antibacterial and antifungal activities are being intensely used as antibiotics and may be effective against infectious diseases such as HIV, conditions of multiple bacterial infections (penicillin, cephalosporines, streptomycin, and vancomycin) or neuropsychiatric sequelae. Research is also being conducted on the general aspects of biophysical and biochemical properties, chemical structures and biotechnological applications of the bioactive substances derived from marine microorganisms, and their potential use as cosmeceuticals and nutraceuticals. This review is an attempt to consolidate the latest studies and critical research in this field, and to showcase the immense competence of marine microbial flora as bioactive metabolite producers. In addition, the present review addresses some effective and novel approaches of procuring marine microbial compounds utilizing the latest screening strategies of drug discovery. Full article
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493 KiB  
Review
Marine Antitumor Drugs: Status, Shortfalls and Strategies
by Ira Bhatnagar and Se-Kwon Kim
Mar. Drugs 2010, 8(10), 2702-2720; https://doi.org/10.3390/md8102702 - 15 Oct 2010
Cited by 126 | Viewed by 13998
Abstract
Cancer is considered as one of the deadliest diseases in the medical field. Apart from the preventive therapies, it is important to find a curative measure which holds no loopholes and acts accurately and precisely to curb cancer. Over the past few decades, [...] Read more.
Cancer is considered as one of the deadliest diseases in the medical field. Apart from the preventive therapies, it is important to find a curative measure which holds no loopholes and acts accurately and precisely to curb cancer. Over the past few decades, there have been advances in this field and there are many antitumor compounds available on the market, which are of natural as well as synthetic origin. Marine chemotherapy is well recognized nowadays and profound development has been achieved by researchers to deal with different molecular pathways of tumors. However, the marine environment has been less explored for the production of safe and novel antitumor compounds. The reason is a number of shortfalls in this field. Though ample reviews cover the importance and applications of various anticancerous compounds from marine natural products, in the present review, we have tried to bring the current status of antitumor research based on marine inhibitors of cancer signaling pathways. In addition, focus has been placed on the shortfalls and probable strategies in the arena of marine antitumor drug discovery. Full article
(This article belongs to the Special Issue Marine Drugs as Antitumour Agents)
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