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Special Issue "Marine Secondary Metabolites"

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A special issue of Marine Drugs (ISSN 1660-3397).

Deadline for manuscript submissions: closed (30 June 2015)

Special Issue Editor

Guest Editor
Prof. Valeria Costantino (Website)

Department of Pharmacy, University of Naples "Federico II", Via Domenico Montesano 49, 80131 Napoli, Italy
Phone: +39081678504
Fax: +39 081 678552
Interests: isolation and stereostructural elucidation of new leads compounds in anti-inflammatory and anti-cancer drug discovery

Special Issue Information

Dear Colleagues,

This special issue is dedicated to Professor Ernesto Fattorusso, one of the pioneers in Chemistry of Marine Natural Products, who passed away in July 2012.

In the last three decades, research on natural products has clearly shown that the chances of finding new bioactive compounds are remarkably higher among the less studied marine organisms than among terrestrial organisms. The biosynthetic capability of marine organisms is amazing, even if the discovery that symbiotic microorganisms are the true producers of many of these compounds provided at least a partial answer. The jointed work of chemists of natural products with pharmacologists gave rise to hundred of publications showing the potentiality of marine natural products as leads in the drug discovery.

This special issue will be focus on recent accomplishments in this field, providing a tool for young researchers that want to approach this terribly interesting world.

Dr. Valeria Costantino
Guest Editor

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Marine Drugs is an international peer-reviewed Open Access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs).

Keywords

  • marine secondary metabolites
  • marine natural products
  • marine terpenes
  • marine polyketides
  • marine glycolipids
  • marine toxins
  • marine fungi
  • marine bacteria
  • sponge-microrganisms symbiosis
  • bioactivity of marine natural products
  • synthesis of marine natural products
  • biogenesis of marine natural products
  • anti-tumor activity
  • anti-inflammatory activity
  • anti-viral activity
  • Published Papers (37 papers)

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    Research

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    Open AccessArticle Mycosporine-Like Amino Acids Promote Wound Healing through Focal Adhesion Kinase (FAK) and Mitogen-Activated Protein Kinases (MAP Kinases) Signaling Pathway in Keratinocytes
    Mar. Drugs 2015, 13(12), 7055-7066; doi:10.3390/md13127056
    Received: 20 August 2015 / Revised: 10 November 2015 / Accepted: 18 November 2015 / Published: 26 November 2015
    Cited by 1 | PDF Full-text (2177 KB) | HTML Full-text | XML Full-text
    Abstract
    Mycosporine-like amino acids (MAAs) are secondary metabolites found in diverse marine, freshwater, and terrestrial organisms. Evidence suggests that MAAs have several beneficial effects on skin homeostasis such as protection against UV radiation and reactive oxygen species (ROS). In addition, MAAs are also [...] Read more.
    Mycosporine-like amino acids (MAAs) are secondary metabolites found in diverse marine, freshwater, and terrestrial organisms. Evidence suggests that MAAs have several beneficial effects on skin homeostasis such as protection against UV radiation and reactive oxygen species (ROS). In addition, MAAs are also involved in the modulation of skin fibroblasts proliferation. However, the regulatory function of MAAs on wound repair in human skin is not yet clearly elucidated. To investigate the roles of MAAs on the wound healing process in human keratinocytes, three MAAs, Shinorine (SH), Mycosporine-glycine (M-Gly), and Porphyra (P334) were purified from Chlamydomonas hedlyei and Porphyra yezoensis. We found that SH, M-Gly, and P334 have significant effects on the wound healing process in human keratinocytes and these effects were mediated by activation of focal adhesion kinases (FAK), extracellular signal-regulated kinases (ERK), and c-Jun N-terminal kinases (JNK). These results suggest that MAAs accelerate wound repair by activating the FAK-MAPK signaling pathways. This study also indicates that MAAs can act as a new wound healing agent and further suggests that MAAs might be a novel biomaterial for wound healing therapies. Full article
    (This article belongs to the Special Issue Marine Secondary Metabolites)
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    Open AccessArticle A New Analogue of Echinomycin and a New Cyclic Dipeptide from a Marine-Derived Streptomyces sp. LS298
    Mar. Drugs 2015, 13(11), 6947-6961; doi:10.3390/md13116947
    Received: 2 July 2015 / Revised: 5 November 2015 / Accepted: 6 November 2015 / Published: 18 November 2015
    PDF Full-text (324 KB) | HTML Full-text | XML Full-text | Supplementary Files
    Abstract
    Quinomycin G (1), a new analogue of echinomycin, together with a new cyclic dipeptide, cyclo-(l-Pro-4-OH-l-Leu) (2), as well as three known antibiotic compounds tirandamycin A (3), tirandamycin B (4) and staurosporine (5), [...] Read more.
    Quinomycin G (1), a new analogue of echinomycin, together with a new cyclic dipeptide, cyclo-(l-Pro-4-OH-l-Leu) (2), as well as three known antibiotic compounds tirandamycin A (3), tirandamycin B (4) and staurosporine (5), were isolated from Streptomyces sp. LS298 obtained from a marine sponge Gelliodes carnosa. The planar and absolute configurations of compounds 1 and 2 were established by MS, NMR spectral data analysis and Marfey’s method. Furthermore, the differences in NMR data of keto-enol tautomers in tirandamycins were discussed for the first time. Antibacterial and anti-tumor activities of compound 1 were measured against 15 drug-sensitive/resistant strains and 12 tumor cell lines. Compound 1 exhibited moderate antibacterial activities against Staphylococcuse pidermidis, S. aureus, Enterococcus faecium, and E. faecalis with the minimum inhibitory concentration (MIC) values ranged from 16 to 64 μg/mL. Moreover, it displayed remarkable anti-tumor activities; the highest activity was observed against the Jurkat cell line (human T-cell leukemia) with an IC50 value of 0.414 μM. Full article
    (This article belongs to the Special Issue Marine Secondary Metabolites)
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    Open AccessArticle Structure Elucidation and in Vitro Toxicity of New Azaspiracids Isolated from the Marine Dinoflagellate Azadinium poporum
    Mar. Drugs 2015, 13(11), 6687-6702; doi:10.3390/md13116687
    Received: 14 April 2015 / Revised: 14 June 2015 / Accepted: 14 October 2015 / Published: 30 October 2015
    Cited by 2 | PDF Full-text (547 KB) | HTML Full-text | XML Full-text | Supplementary Files
    Abstract
    Two strains of Azadinium poporum, one from the Korean West coast and the other from the North Sea, were mass cultured for isolation of new azaspiracids. Approximately 0.9 mg of pure AZA-36 (1) and 1.3 mg of pure AZA-37 [...] Read more.
    Two strains of Azadinium poporum, one from the Korean West coast and the other from the North Sea, were mass cultured for isolation of new azaspiracids. Approximately 0.9 mg of pure AZA-36 (1) and 1.3 mg of pure AZA-37 (2) were isolated from the Korean (870 L) and North Sea (120 L) strains, respectively. The structures were determined to be 3-hydroxy-8-methyl-39-demethyl-azaspiracid-1 (1) and 3-hydroxy-7,8-dihydro-39-demethyl-azaspiracid-1 (2) by 1H- and 13C-NMR. Using the Jurkat T lymphocyte cell toxicity assay, (1) and (2) were found to be 6- and 3-fold less toxic than AZA-1, respectively. Full article
    (This article belongs to the Special Issue Marine Secondary Metabolites)
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    Open AccessArticle Alkaloids with Cardiovascular Effects from the Marine-Derived Fungus Penicillium expansum Y32
    Mar. Drugs 2015, 13(10), 6489-6504; doi:10.3390/md13106489
    Received: 22 August 2015 / Revised: 2 October 2015 / Accepted: 9 October 2015 / Published: 22 October 2015
    Cited by 1 | PDF Full-text (1182 KB) | HTML Full-text | XML Full-text | Supplementary Files
    Abstract
    Three new alkaloids (1, 4 and 8), together with nine known analogues (2, 3, 5–7, and 9–12), were isolated from the marine-derived fungus Penicillium expansum Y32. Their structures including the absolute configurations were elucidated by spectroscopic and Mosher’s and Marfey’s methods, along [...] Read more.
    Three new alkaloids (1, 4 and 8), together with nine known analogues (2, 3, 5–7, and 9–12), were isolated from the marine-derived fungus Penicillium expansum Y32. Their structures including the absolute configurations were elucidated by spectroscopic and Mosher’s and Marfey’s methods, along with quantum electronic circular dichroism (ECD) calculations. Each of the compounds was evaluated for cardiovascular effects in a live zebrafish model. All of the compounds showed a significant mitigative effect on bradycardia caused by astemizole (ASM) in the heart rate experiments. Compounds 4–6 and 8–12 exhibited potent vasculogenetic activity in vasculogenesis experiments. This is the first study to report that these types of compounds show cardiovascular effects in zebrafish. The results suggest that these compounds could be promising candidates for cardiovascular disease lead compounds. Full article
    (This article belongs to the Special Issue Marine Secondary Metabolites)
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    Open AccessArticle Gliotoxin Inhibits Proliferation and Induces Apoptosis in Colorectal Cancer Cells
    Mar. Drugs 2015, 13(10), 6259-6273; doi:10.3390/md13106259
    Received: 26 June 2015 / Revised: 27 August 2015 / Accepted: 24 September 2015 / Published: 2 October 2015
    Cited by 1 | PDF Full-text (1668 KB) | HTML Full-text | XML Full-text
    Abstract
    The discovery of new bioactive compounds from marine natural sources is very important in pharmacological research. Here we developed a Wnt responsive luciferase reporter assay to screen small molecule inhibitors of cancer associated constitutive Wnt signaling pathway. We identified that gliotoxin (GTX) [...] Read more.
    The discovery of new bioactive compounds from marine natural sources is very important in pharmacological research. Here we developed a Wnt responsive luciferase reporter assay to screen small molecule inhibitors of cancer associated constitutive Wnt signaling pathway. We identified that gliotoxin (GTX) and some of its analogues, the secondary metabolites from marine fungus Neosartorya pseufofischeri, acted as inhibitors of the Wnt signaling pathway. In addition, we found that GTX downregulated the β-catenin levels in colorectal cancer cells with inactivating mutations of adenomatous polyposis coli (APC) or activating mutations of β-catenin. Furthermore, we demonstrated that GTX induced growth inhibition and apoptosis in multiple colorectal cancer cell lines with mutations of the Wnt signaling pathway. Together, we illustrated a practical approach to identify small-molecule inhibitors of the Wnt signaling pathway and our study indicated that GTX has therapeutic potential for the prevention or treatment of Wnt dependent cancers and other Wnt related diseases. Full article
    (This article belongs to the Special Issue Marine Secondary Metabolites)
    Open AccessArticle Development and Application of a Novel SPE-Method for Bioassay-Guided Fractionation of Marine Extracts
    Mar. Drugs 2015, 13(9), 5736-5749; doi:10.3390/md13095736
    Received: 16 June 2015 / Revised: 15 August 2015 / Accepted: 28 August 2015 / Published: 11 September 2015
    Cited by 2 | PDF Full-text (737 KB) | HTML Full-text | XML Full-text | Supplementary Files
    Abstract
    The biological diversity of marine habitats is a unique source of chemical compounds with potential use as pharmaceuticals, cosmetics and dietary supplements. However, biological screening and chemical analysis of marine extracts pose specific technical constraints and require adequate sample preparation. Here we [...] Read more.
    The biological diversity of marine habitats is a unique source of chemical compounds with potential use as pharmaceuticals, cosmetics and dietary supplements. However, biological screening and chemical analysis of marine extracts pose specific technical constraints and require adequate sample preparation. Here we report an improved method on Solid Phase Extraction (SPE) to fractionate organic extracts containing high concentration of salt that hampers the recovery of secondary metabolites. The procedure uses a water suspension to load the extracts on a poly(styrene-divynylbenzene)-based support and a stepwise organic solvent elution to effectively desalt and fractionate the organic components. The novel protocol has been tested on MeOH-soluble material from three model organisms (Reniera sarai, Dendrilla membranosa and Amphidinium carterae) and was validated on a small panel of 47 marine samples, including sponges and protists, within discovery programs for identification of immuno-stimulatory and anti-infective natural products. Full article
    (This article belongs to the Special Issue Marine Secondary Metabolites)
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    Open AccessArticle Sphingosines Derived from Marine Sponge as Potential Multi-Target Drug Related to Disorders in Cancer Development
    Mar. Drugs 2015, 13(9), 5552-5563; doi:10.3390/md13095552
    Received: 30 May 2015 / Revised: 14 August 2015 / Accepted: 14 August 2015 / Published: 25 August 2015
    Cited by 1 | PDF Full-text (803 KB) | HTML Full-text | XML Full-text
    Abstract
    Haliclona tubifera, marine sponge species abundant in Brazilian coastline, presents only a few papers published in the literature. Recently, we have reported the isolation of two modified C18 sphingoid bases: (2R,3R,6R,7Z)-2-aminooctadec-7-ene-1,3, 6-triol and [...] Read more.
    Haliclona tubifera, marine sponge species abundant in Brazilian coastline, presents only a few papers published in the literature. Recently, we have reported the isolation of two modified C18 sphingoid bases: (2R,3R,6R,7Z)-2-aminooctadec-7-ene-1,3, 6-triol and and (2R,3R,6R)-2-aminooctadec-1,3,6-triol. In order to continue our research, in this work aimed at the biological investigation of fractions that led to the isolation of these compounds. We evaluated the cytotoxic effect of marine sponge H. tubifera fractions in glioma (U87) and neuroblastoma (SH-SY5Y) human cell lines. In addition, considering the link between cancer, imbalance of reactive oxygen species and coagulation disorders, we also investigated the in vitro effects on blood coagulation and their redox properties. We showed that the ethyl acetate (EtOAc) fraction, rich in sphingoid bases, had important cytotoxic effects in both cancer cell lines with an IC50 < 15 μg/mL and also can inhibit the production of peroxyl radicals. Interestingly, this fraction increased the recalcification time of human blood, showing anticoagulant properties. The present study indicates the sphingosines fraction as a promising source of chemical prototypes, especially multifunctional drugs in cancer therapy. Full article
    (This article belongs to the Special Issue Marine Secondary Metabolites)
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    Open AccessArticle Hormaomycins B and C: New Antibiotic Cyclic Depsipeptides from a Marine Mudflat-Derived Streptomyces sp.
    Mar. Drugs 2015, 13(8), 5187-5200; doi:10.3390/md13085187
    Received: 29 June 2015 / Revised: 28 July 2015 / Accepted: 30 July 2015 / Published: 14 August 2015
    Cited by 1 | PDF Full-text (336 KB) | HTML Full-text | XML Full-text | Supplementary Files
    Abstract
    Alterations in microbial culture conditions may trigger the production of diverse bioactive secondary metabolites. While applying various culture conditions and monitoring secondary metabolite profiles using LC/MS, hormaomycins B and C (1 and 2) were discovered from a marine mudflat-derived actinomycete, [...] Read more.
    Alterations in microbial culture conditions may trigger the production of diverse bioactive secondary metabolites. While applying various culture conditions and monitoring secondary metabolite profiles using LC/MS, hormaomycins B and C (1 and 2) were discovered from a marine mudflat-derived actinomycete, Streptomyces sp., collected in Mohang, Korea. The planar structures of the hormaomycins, which bear structurally-unique units, such as 4-(Z)-propenylproline, 3-(2-nitrocyclopropyl)alanine, 5-chloro-1-hydroxypyrrol-2-carboxylic acid and b-methylphenylalanine, were established as the first natural analogues belonging to the hormaomycin peptide class. The absolute configurations of 1 and 2 were deduced by comparing their CD spectra with that of hormaomycin. These hormaomycins exhibited significant inhibitory effects against various pathogenic Gram-positive and Gram-negative bacteria. Full article
    (This article belongs to the Special Issue Marine Secondary Metabolites)
    Open AccessArticle Chemistry of Renieramycins. Part 14: Total Synthesis of Renieramycin I and Practical Synthesis of Cribrostatin 4 (Renieramycin H)
    Mar. Drugs 2015, 13(8), 4915-4933; doi:10.3390/md13084915
    Received: 27 June 2015 / Revised: 21 July 2015 / Accepted: 22 July 2015 / Published: 6 August 2015
    Cited by 2 | PDF Full-text (443 KB) | HTML Full-text | XML Full-text | Supplementary Files
    Abstract
    The first total synthesis of (±)-renieramycin I, which was isolated from the Indian bright blue sponge Haliclona cribricutis, is described. The key step is the selenium oxide oxidation of pentacyclic bis-p-quinone derivative (3) stereo- and regioselectively. We [...] Read more.
    The first total synthesis of (±)-renieramycin I, which was isolated from the Indian bright blue sponge Haliclona cribricutis, is described. The key step is the selenium oxide oxidation of pentacyclic bis-p-quinone derivative (3) stereo- and regioselectively. We also report a large-scale synthesis of cribrostatin 4 (renieramycin H) via the C3-C4 double bond formation in an early stage based on the Avendaño’s protocol, from readily available 1-acetyl-3-(3-methyl-2,4,5-trimethylphenyl)methyl-piperazine-2,5-dione (8) in 18 steps (8.3% overall yield). The synthesis provides unambiguous evidence supporting the original structure of renieramycin I. Full article
    (This article belongs to the Special Issue Marine Secondary Metabolites)
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    Open AccessArticle Monacyclinones, New Angucyclinone Metabolites Isolated from Streptomyces sp. M7_15 Associated with the Puerto Rican Sponge Scopalina ruetzleri
    Mar. Drugs 2015, 13(8), 4682-4700; doi:10.3390/md13084682
    Received: 24 April 2015 / Revised: 29 June 2015 / Accepted: 2 July 2015 / Published: 29 July 2015
    Cited by 2 | PDF Full-text (425 KB) | HTML Full-text | XML Full-text | Supplementary Files
    Abstract
    During an investigation of new actinomycete species from Caribbean sponges for novel bioactive natural products, frigocyclinone (1), dimethyldehydrorabelomycin (3) and six new angucyclinone derivatives were isolated from Streptomyces sp. strain M7_15 associated with the sponge Scopalina ruetzleri. [...] Read more.
    During an investigation of new actinomycete species from Caribbean sponges for novel bioactive natural products, frigocyclinone (1), dimethyldehydrorabelomycin (3) and six new angucyclinone derivatives were isolated from Streptomyces sp. strain M7_15 associated with the sponge Scopalina ruetzleri. Of these, monacyclinones A–B (45) contain the core ring structure of dehydrorabelomycin (2) with the aminodeoxysugar found in frigocyclinone (1). Monacyclinone C (6) is a hydroxylated variant of frigocyclinone (1) and monacyclinone D (7) is a Baeyer Villiger derivative of (6) which also exists as the open chain hydrolysis product monacyclinone E (8). Monacyclinone F (9) contains two unique epoxide rings attached to the angucyclinone moiety and an additional aminodeoxysugar attached through an angular oxygen bond. All structures were confirmed through spectral analyses. Activity against rhabdomycosarcoma cancer cells (SJCRH30) after 48 h of treatment was observed with frigocyclinone (1; EC50 = 5.2 µM), monacyclinone C (6; 160 µM), monacyclinone E (8; 270 µM), and monacyclinone F (9; 0.73 µM). The strongest bioactivity against rhabdomycosarcoma cancer cells and gram-positive bacteria was exhibited by compound 9, suggesting that the extra aminodeoxysugar subunit is important for biological activity. Full article
    (This article belongs to the Special Issue Marine Secondary Metabolites)
    Open AccessArticle Crambescin C1 Exerts a Cytoprotective Effect on HepG2 Cells through Metallothionein Induction
    Mar. Drugs 2015, 13(8), 4633-4653; doi:10.3390/md13084633
    Received: 13 April 2015 / Revised: 19 June 2015 / Accepted: 19 June 2015 / Published: 27 July 2015
    Cited by 1 | PDF Full-text (4961 KB) | HTML Full-text | XML Full-text | Supplementary Files
    Abstract
    The Mediterranean marine sponge Crambe crambe is the source of two families of guanidine alkaloids known as crambescins and crambescidins. Some of the biological effects of crambescidins have been previously reported while crambescins have undergone little study. Taking this into account, we [...] Read more.
    The Mediterranean marine sponge Crambe crambe is the source of two families of guanidine alkaloids known as crambescins and crambescidins. Some of the biological effects of crambescidins have been previously reported while crambescins have undergone little study. Taking this into account, we performed comparative transcriptome analysis to examine the effect of crambescin-C1 (CC1) on human tumor hepatocarcinoma cells HepG2 followed by validation experiments to confirm its predicted biological activities. We report herein that, while crambescin-A1 has a minor effect on these cells, CC1 protects them against oxidative injury by means of metallothionein induction even at low concentrations. Additionally, at high doses, CC1 arrests the HepG2 cell cycle in G0/G1 and thus inhibits tumor cell proliferation. The findings presented here provide the first detailed approach regarding the different effects of crambescins on tumor cells and provide a basis for future studies on other possible cellular mechanisms related to these bioactivities. Full article
    (This article belongs to the Special Issue Marine Secondary Metabolites)
    Open AccessArticle Four New Sulfated Polar Steroids from the Far Eastern Starfish Leptasterias ochotensis: Structures and Activities
    Mar. Drugs 2015, 13(7), 4418-4435; doi:10.3390/md13074418
    Received: 6 May 2015 / Revised: 1 July 2015 / Accepted: 9 July 2015 / Published: 16 July 2015
    Cited by 1 | PDF Full-text (870 KB) | HTML Full-text | XML Full-text | Supplementary Files
    Abstract
    Three new sulfated steroid monoglycosides, leptaochotensosides A–C (13), and a new sulfated polyhydroxylated steroid (4) were isolated from the alcoholic extract of the Far Eastern starfish Leptasterias ochotensis. The structures of compounds 14 [...] Read more.
    Three new sulfated steroid monoglycosides, leptaochotensosides A–C (13), and a new sulfated polyhydroxylated steroid (4) were isolated from the alcoholic extract of the Far Eastern starfish Leptasterias ochotensis. The structures of compounds 14 were established by extensive nuclear magnetic resonance (NMR) and electrospray ionization mass spectrometry (ESIMS) analyses and chemical transformations. Although the isolated compounds did not show any apparent cytotoxicity against melanoma RPMI-7951 and breast cancer T-47D cell lines, leptaochotensoside A (1) demonstrated inhibition of T-47D cell colony formation in a soft agar clonogenic assay at nontoxic doses. In addition, this compound decreased the epidermal growth factor (EGF)-induced colony formation of mouse epidermal JB6 Cl41 cells. The cancer preventive action of 1 is realized through regulation of mitogen-activated protein kinase (MAPK) signaling pathway. Full article
    (This article belongs to the Special Issue Marine Secondary Metabolites)
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    Open AccessCommunication New α-Glucosidase Inhibitory Triterpenic Acid from Marine Macro Green Alga Codium dwarkense Boergs
    Mar. Drugs 2015, 13(7), 4344-4356; doi:10.3390/md13074344
    Received: 6 June 2015 / Revised: 29 June 2015 / Accepted: 6 July 2015 / Published: 14 July 2015
    Cited by 1 | PDF Full-text (830 KB) | HTML Full-text | XML Full-text | Supplementary Files
    Abstract
    The marine ecosystem has been a key resource for secondary metabolites with promising biological roles. In the current study, bioassay-guided phytochemical investigations were carried out to assess the presence of enzyme inhibitory chemical constituents from the methanolic extract of marine green alga— [...] Read more.
    The marine ecosystem has been a key resource for secondary metabolites with promising biological roles. In the current study, bioassay-guided phytochemical investigations were carried out to assess the presence of enzyme inhibitory chemical constituents from the methanolic extract of marine green alga—Codium dwarkense. The bioactive fractions were further subjected to chromatographic separations, which resulted in the isolation of a new triterpenic acid; dwarkenoic acid (1) and the known sterols; androst-5-en-3β-ol (2), stigmasta-5,25-dien-3β,7α-diol (3), ergosta-5,25-dien-3β-ol (4), 7-hydroxystigmasta-4,25-dien-3-one-7-O-β-d-fucopyranoside (5), 7-hydroxystigmasta-4,25-dien-3-one (6), and stigmasta-5,25-dien-3β-ol (7). The structure elucidation of the new compound was carried out by combined mass spectrometry and 1D (1H and 13C) and 2D (HSQC, HMBC, COSY, and NOESY) NMR spectroscopic data. The sub-fractions and pure constituents were assayed for enzymatic inhibition of alpha-glucosidase. Compound 1 showed significant inhibition at all concentrations. Compounds 2, 3, 5, and 7 exhibited a dose-dependent response, whereas compounds 46 showed moderate inhibition. Utilizing such marine-derived biological resources could lead to drug discoveries related to anti-diabetics. Full article
    (This article belongs to the Special Issue Marine Secondary Metabolites)
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    Open AccessArticle Sulfated Galactan from Palisada flagellifera Inhibits Toxic Effects of Lachesis muta Snake Venom
    Mar. Drugs 2015, 13(6), 3761-3775; doi:10.3390/md13063761
    Received: 8 April 2015 / Revised: 20 May 2015 / Accepted: 25 May 2015 / Published: 11 June 2015
    Cited by 1 | PDF Full-text (639 KB) | HTML Full-text | XML Full-text
    Abstract
    In Brazil, snakebites are a public health problem and accidents caused by Lachesis muta have the highest mortality index. Envenomation by L. muta is characterized by systemic (hypotension, bleeding and renal failure) and local effects (necrosis, pain and edema). The treatment to [...] Read more.
    In Brazil, snakebites are a public health problem and accidents caused by Lachesis muta have the highest mortality index. Envenomation by L. muta is characterized by systemic (hypotension, bleeding and renal failure) and local effects (necrosis, pain and edema). The treatment to reverse the evolution of all the toxic effects is performed by injection of antivenom. However, such therapy does not effectively neutralize tissue damage or any other local effect, since in most cases victims delay seeking appropriate medical care. In this way, alternative therapies are in demand, and molecules from natural sources have been exhaustively tested. In this paper, we analyzed the inhibitory effect of a sulfated galactan obtained from the red seaweed Palisada flagellifera against some toxic activities of L. muta venom. Incubation of sulfated galactan with venom resulted in inhibition of hemolysis, coagulation, proteolysis, edema and hemorrhage. Neutralization of hemorrhage was also observed when the galactan was administered after or before the venom injection; thus mimicking a real in vivo situation. Moreover, the galactan blocked the edema caused by a phospholipase A2 isolated from the same venom. Therefore, the galactan from P. flagellifera may represent a promising tool to treat envenomation by L. muta as a coadjuvant for the conventional antivenom. Full article
    (This article belongs to the Special Issue Marine Secondary Metabolites)
    Open AccessArticle Myrothecols G and H, Two New Analogues of the Marine-Derived Quinone Sesquiterpene Penicilliumin A
    Mar. Drugs 2015, 13(6), 3360-3367; doi:10.3390/md13063360
    Received: 18 April 2015 / Accepted: 20 May 2015 / Published: 27 May 2015
    Cited by 1 | PDF Full-text (306 KB) | HTML Full-text | XML Full-text | Supplementary Files
    Abstract
    Two new quinone sesquiterpenes named myrothecols G and H (1 and 2), a pair of C-1′ diastereomers of 13-hydroxyl penicilliumin A, were isolated from the mycelia solid cultures of Myrothecium sp. SC0265. Their structures, including the absolute configurations, were established [...] Read more.
    Two new quinone sesquiterpenes named myrothecols G and H (1 and 2), a pair of C-1′ diastereomers of 13-hydroxyl penicilliumin A, were isolated from the mycelia solid cultures of Myrothecium sp. SC0265. Their structures, including the absolute configurations, were established on the basis of the spectroscopic data combining with the theoretical conformational analysis. The cytotoxic activities of 1 and 2 were tested against a panel of human tumor cell lines. Full article
    (This article belongs to the Special Issue Marine Secondary Metabolites)
    Open AccessArticle Capgermacrenes A and B, Bioactive Secondary Metabolites from a Bornean Soft Coral, Capnella sp.
    Mar. Drugs 2015, 13(5), 3103-3115; doi:10.3390/md13053103
    Received: 23 February 2015 / Revised: 2 May 2015 / Accepted: 5 May 2015 / Published: 19 May 2015
    PDF Full-text (659 KB) | HTML Full-text | XML Full-text | Supplementary Files
    Abstract
    Two new bicyclogermacrenes, capgermacrenes A (1) and B (2), were isolated with two known compounds, palustrol (3) and litseagermacrane (4), from a population of Bornean soft coral Capnella sp. The structures of these metabolites [...] Read more.
    Two new bicyclogermacrenes, capgermacrenes A (1) and B (2), were isolated with two known compounds, palustrol (3) and litseagermacrane (4), from a population of Bornean soft coral Capnella sp. The structures of these metabolites were elucidated based on spectroscopic data. Compound 1 was found to inhibit the accumulation of the LPS-induced pro-inflammatory IL-1b and NO production by down-regulating the expression of iNOS protein in RAW 264.7 macrophages. Full article
    (This article belongs to the Special Issue Marine Secondary Metabolites)
    Open AccessArticle Anti-Inflammatory and Analgesic Effects of the Marine-Derived Compound Excavatolide B Isolated from the Culture-Type Formosan Gorgonian Briareum excavatum
    Mar. Drugs 2015, 13(5), 2559-2579; doi:10.3390/md13052559
    Received: 18 March 2015 / Revised: 17 April 2015 / Accepted: 20 April 2015 / Published: 27 April 2015
    Cited by 3 | PDF Full-text (1266 KB) | HTML Full-text | XML Full-text
    Abstract
    In recent years, several marine-derived compounds have been clinically evaluated. Diterpenes are secondary metabolites from soft coral that exhibit anti-inflammatory, anti-tumor and cytotoxic activities. In the present study, we isolated a natural diterpene product, excavatolide B, from cultured Formosan gorgonian Briareum excavatum [...] Read more.
    In recent years, several marine-derived compounds have been clinically evaluated. Diterpenes are secondary metabolites from soft coral that exhibit anti-inflammatory, anti-tumor and cytotoxic activities. In the present study, we isolated a natural diterpene product, excavatolide B, from cultured Formosan gorgonian Briareum excavatum and investigated its anti-inflammatory activities. We found that excavatolide B significantly inhibited the mRNA expression of the proinflammatory mediators, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in lipopolysaccharide (LPS)-challenged murine macrophages (RAW 264.7). We also examined the anti-inflammatory and anti-nociceptive effects of excavatolide B on intraplantar carrageenan-induced inflammatory responses. Excavatolide B was found to significantly attenuate carrageenan-induced nociceptive behaviors, mechanical allodynia, thermal hyperalgesia, weight bearing deficits and paw edema. In addition, excavatolide B inhibited iNOS, as well as the infiltration of immune cells in carrageenan-induced inflammatory paw tissue. Full article
    (This article belongs to the Special Issue Marine Secondary Metabolites)
    Open AccessArticle Synthesis and Bioactivity of Luffarin I
    Mar. Drugs 2015, 13(4), 2407-2423; doi:10.3390/md13042407
    Received: 19 February 2015 / Revised: 20 March 2015 / Accepted: 7 April 2015 / Published: 20 April 2015
    Cited by 3 | PDF Full-text (660 KB) | HTML Full-text | XML Full-text | Supplementary Files
    Abstract
    The first synthesis of Luffarin I, sesterterpenolide isolated from sponge Luffariella geometrica, has been accomplished from commercially available sclareol. The key strategy involved in this synthesis is the diastereoselective reduction of an intermediate ketone. Luffarin I against human solid tumor cell [...] Read more.
    The first synthesis of Luffarin I, sesterterpenolide isolated from sponge Luffariella geometrica, has been accomplished from commercially available sclareol. The key strategy involved in this synthesis is the diastereoselective reduction of an intermediate ketone. Luffarin I against human solid tumor cell lines showed antiproliferative activities (GI50) in the range 12–17 μM. Full article
    (This article belongs to the Special Issue Marine Secondary Metabolites)
    Open AccessArticle Seco-Taondiol, an Unusual Meroterpenoid from the Chilean Seaweed Stypopodium flabelliforme and Its Gastroprotective Effect in Mouse Model
    Mar. Drugs 2015, 13(4), 1726-1738; doi:10.3390/md13041726
    Received: 22 January 2015 / Revised: 1 March 2015 / Accepted: 20 March 2015 / Published: 30 March 2015
    Cited by 1 | PDF Full-text (566 KB) | HTML Full-text | XML Full-text | Supplementary Files
    Abstract
    Ten known meroterpenoids and the new meroterpenoid 7 were isolated from the Chilean seaweed Stypopodium flabelliforme as their acetylated derivatives. Furthermore, the known metabolite taondiol has been isolated for the first time from this species. The molecular structure of the new metabolite [...] Read more.
    Ten known meroterpenoids and the new meroterpenoid 7 were isolated from the Chilean seaweed Stypopodium flabelliforme as their acetylated derivatives. Furthermore, the known metabolite taondiol has been isolated for the first time from this species. The molecular structure of the new metabolite was determined by spectroscopic methods based on 1D- and 2D-NMR. Isolation of 7 represents a key step toward a better understanding of the biogenesis of this class of meroterpenoids. Among the meroditerpenoids isolated, stypodiol, isoepitaondiol, epitaondiol and sargaol exhibited gastroprotective activity on the HCl/Ethanol-induced gastric lesions model in mice. Regarding the mode of gastroprotective action, the activity of epitaondiol was reversed significantly when animals were pretreated with indomethacin, N-ethylmaleimide and N-nitro-l-arginine methyl ester (L-NAME) suggesting that prostaglandins, sulfhydryl groups and nitric oxide are involved in their mode of gastroprotective action. In the case of sargaol the gastroprotective activity was attenuated with indomethacin and N-ethylmaleimide, which suggests that prostaglandins and sulfhydryl groups are also involved in the mode of action using this model. Full article
    (This article belongs to the Special Issue Marine Secondary Metabolites)
    Open AccessArticle Isolation and Assessment of the in Vitro Anti-Tumor Activity of Smenothiazole A and B, Chlorinated Thiazole-Containing Peptide/Polyketides from the Caribbean Sponge, Smenospongia aurea
    Mar. Drugs 2015, 13(1), 444-459; doi:10.3390/md13010444
    Received: 3 December 2014 / Accepted: 4 January 2015 / Published: 16 January 2015
    Cited by 5 | PDF Full-text (877 KB) | HTML Full-text | XML Full-text | Supplementary Files
    Abstract
    The study of the secondary metabolites contained in the organic extract of Caribbean sponge Smenospongia aurea led to the isolation of smenothiazole A (3) and B (4), hybrid peptide/polyketide compounds. Assays performed using four solid tumor cell lines [...] Read more.
    The study of the secondary metabolites contained in the organic extract of Caribbean sponge Smenospongia aurea led to the isolation of smenothiazole A (3) and B (4), hybrid peptide/polyketide compounds. Assays performed using four solid tumor cell lines showed that smenothiazoles exert a potent cytotoxic activity at nanomolar levels, with selectivity over ovarian cancer cells and a pro-apoptotic mechanism. Full article
    (This article belongs to the Special Issue Marine Secondary Metabolites)
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    Open AccessArticle Polyketide Synthases in the Microbiome of the Marine Sponge Plakortis halichondrioides: A Metagenomic Update
    Mar. Drugs 2014, 12(11), 5425-5440; doi:10.3390/md12115425
    Received: 9 September 2014 / Revised: 4 November 2014 / Accepted: 6 November 2014 / Published: 14 November 2014
    Cited by 9 | PDF Full-text (1646 KB) | HTML Full-text | XML Full-text | Supplementary Files
    Abstract
    Sponge-associated microorganisms are able to assemble the complex machinery for the production of secondary metabolites such as polyketides, the most important class of marine natural products from a drug discovery perspective. A comprehensive overview of polyketide biosynthetic genes of the sponge Plakortis [...] Read more.
    Sponge-associated microorganisms are able to assemble the complex machinery for the production of secondary metabolites such as polyketides, the most important class of marine natural products from a drug discovery perspective. A comprehensive overview of polyketide biosynthetic genes of the sponge Plakortis halichondrioides and its symbionts was obtained in the present study by massively parallel 454 pyrosequencing of complex and heterogeneous PCR (Polymerase Chain Reaction) products amplified from the metagenomic DNA of a specimen of P. halichondrioides collected in the Caribbean Sea. This was accompanied by a survey of the bacterial diversity within the sponge. In line with previous studies, sequences belonging to supA and swfA, two widespread sponge-specific groups of polyketide synthase (PKS) genes were dominant. While they have been previously reported as belonging to Poribacteria (a novel bacterial phylum found exclusively in sponges), re-examination of current genomic sequencing data showed supA and swfA not to be present in the poribacterial genome. Several non-supA, non-swfA type-I PKS fragments were also identified. A significant portion of these fragments resembled type-I PKSs from protists, suggesting that bacteria may not be the only source of polyketides from P. halichondrioides, and that protistan PKSs should receive further investigation as a source of novel polyketides. Full article
    (This article belongs to the Special Issue Marine Secondary Metabolites)
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    Open AccessArticle Smenamides A and B, Chlorinated Peptide/Polyketide Hybrids Containing a Dolapyrrolidinone Unit from the Caribbean Sponge Smenospongia aurea. Evaluation of Their Role as Leads in Antitumor Drug Research
    Mar. Drugs 2013, 11(11), 4451-4463; doi:10.3390/md11114451
    Received: 27 September 2013 / Revised: 25 October 2013 / Accepted: 25 October 2013 / Published: 8 November 2013
    Cited by 5 | PDF Full-text (553 KB) | HTML Full-text | XML Full-text | Supplementary Files
    Abstract
    An in-depth study of the secondary metabolites contained in the Caribbean sponge Smenospongia aurea led to the isolation of smenamide A (1) and B (2), hybrid peptide/polyketide compounds containing a dolapyrrolidinone unit. Their structures were elucidated using high-resolution [...] Read more.
    An in-depth study of the secondary metabolites contained in the Caribbean sponge Smenospongia aurea led to the isolation of smenamide A (1) and B (2), hybrid peptide/polyketide compounds containing a dolapyrrolidinone unit. Their structures were elucidated using high-resolution ESI-MS/MS and homo- and heteronuclear 2D NMR experiments. Structures of smenamides suggested that they are products of the cyanobacterial metabolism, and 16S rRNA metagenomic analysis detected Synechococcus spongiarum as the only cyanobacterium present in S. aurea. Smenamides showed potent cytotoxic activity at nanomolar levels on lung cancer Calu-1 cells, which for compound 1 is exerted through a clear pro-apoptotic mechanism. This makes smenamides promising leads for antitumor drug design. Full article
    (This article belongs to the Special Issue Marine Secondary Metabolites)
    Open AccessArticle Cyclodextrin Formulation of the Marine Natural Product Pseudopterosin A Uncovers Optimal Pharmacodynamics in Proliferation Studies of Human Umbilical Vein Endothelial Cells
    Mar. Drugs 2013, 11(9), 3258-3271; doi:10.3390/md11093258
    Received: 5 July 2013 / Revised: 13 August 2013 / Accepted: 14 August 2013 / Published: 26 August 2013
    Cited by 5 | PDF Full-text (842 KB) | HTML Full-text | XML Full-text | Supplementary Files
    Abstract
    Pseudopterosin A (PsA) treatment of growth factor depleted human umbilical vein endothelial cell (HUVEC) cultures formulated in hydroxypropyl-β-cyclodextrin (HPβCD) for 42 h unexpectedly produced a 25% increase in cell proliferation (EC50 = 1.34 × 10−8 M). Analysis of dose response [...] Read more.
    Pseudopterosin A (PsA) treatment of growth factor depleted human umbilical vein endothelial cell (HUVEC) cultures formulated in hydroxypropyl-β-cyclodextrin (HPβCD) for 42 h unexpectedly produced a 25% increase in cell proliferation (EC50 = 1.34 × 10−8 M). Analysis of dose response curves revealed pseudo-first order saturation kinetics, and the uncoupling of cytotoxicity from cell proliferation, thereby resulting in a widening of the therapeutic index. The formulation of PsA into HPβCD produced a 200-fold increase in potency over a DMSO formulation; we propose this could result from a constrained presentation of PsA to the receptor, which would limit non-specific binding. These results support the hypothesis that the non-specific receptor binding of PsA when formulated in DMSO has ostensibly masked prior estimates of specific activity, potency, and mechanism. Collectively, these results suggest that the formulation of PsA and compounds of similar chemical properties in HPβCD could result in significant pharmacological findings that may otherwise be obscured when using solvents such as DMSO. Full article
    (This article belongs to the Special Issue Marine Secondary Metabolites)
    Open AccessArticle Balibalosides, an Original Family of Glucosylated Sesterterpenes Produced by the Mediterranean Sponge Oscarella balibaloi
    Mar. Drugs 2013, 11(5), 1477-1489; doi:10.3390/md11051477
    Received: 25 March 2013 / Revised: 9 April 2013 / Accepted: 22 April 2013 / Published: 6 May 2013
    Cited by 7 | PDF Full-text (555 KB) | HTML Full-text | XML Full-text | Supplementary Files
    Abstract
    The chemical investigation of the recently described Mediterranean Homoscleromorpha sponge Oscarella balibaloi revealed an original family of five closely related glucosylated sesterterpenes 14, named balibalosides. Their structure elucidation was mainly inferred from NMR and HRMS data analyses. Balibalosides differ [...] Read more.
    The chemical investigation of the recently described Mediterranean Homoscleromorpha sponge Oscarella balibaloi revealed an original family of five closely related glucosylated sesterterpenes 14, named balibalosides. Their structure elucidation was mainly inferred from NMR and HRMS data analyses. Balibalosides differ by the pattern of acetyl substitutions on the three sugar residues linked to the same aglycone sesterterpenoid core. From a biosynthetic perspective, these compounds may represent intermediates in the pathways leading to more complex sesterterpenes frequently found in Dictyoceratida, a sponge Order belonging to Demospongiae, a clade which is phylogenetically distinct from the Homoscleromorpha. While steroid and triterpenoid saponins were already well known from marine sponges, balibalosides are the first examples of glycosilated sesterterpenes. Full article
    (This article belongs to the Special Issue Marine Secondary Metabolites)
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    Open AccessArticle Potential Chemopreventive Activity of a New Macrolide Antibiotic from a Marine-Derived Micromonospora sp.
    Mar. Drugs 2013, 11(4), 1152-1161; doi:10.3390/md11041152
    Received: 25 January 2013 / Revised: 8 March 2013 / Accepted: 11 March 2013 / Published: 3 April 2013
    Cited by 7 | PDF Full-text (501 KB) | HTML Full-text | XML Full-text | Supplementary Files
    Abstract
    Agents capable of inducing phase II enzymes such as quinone reductase 1 (QR1) are known to have the potential of mediating cancer chemopreventive activity. As part of a program to discover novel phase II enzyme-inducing molecules, we identified a marine-derived actinomycete strain [...] Read more.
    Agents capable of inducing phase II enzymes such as quinone reductase 1 (QR1) are known to have the potential of mediating cancer chemopreventive activity. As part of a program to discover novel phase II enzyme-inducing molecules, we identified a marine-derived actinomycete strain (CNJ-878) that exhibited activity with cultured Hepa 1c1c7 cells. Based on this activity, a new macrolide, juvenimicin C (1), as well as 5-O-α-l-rhamnosyltylactone (2), were isolated from the culture broth of a Micromonospora sp. Compound 1 enhanced QR1 enzyme activity and glutathione levels by two-fold with CD values of 10.1 and 27.7 μM, respectively. In addition, glutathione reductase and glutathione peroxidase activities were elevated. This is the first reported member of the macrolide class of antibiotics found to mediate these responses. Full article
    (This article belongs to the Special Issue Marine Secondary Metabolites)
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    Open AccessArticle Thalassospiramide G, a New γ-Amino-Acid-Bearing Peptide from the Marine Bacterium Thalassospira sp.
    Mar. Drugs 2013, 11(3), 611-622; doi:10.3390/md11030611
    Received: 13 December 2012 / Revised: 29 January 2013 / Accepted: 6 February 2013 / Published: 26 February 2013
    Cited by 6 | PDF Full-text (627 KB) | HTML Full-text | XML Full-text | Supplementary Files
    Abstract
    In the chemical investigation of marine unicellular bacteria, a new peptide, thalassospiramide G (1), along with thalassospiramides A and D (23), was discovered from a large culture of Thalassospira sp. The structure of thalassospiramide G, bearing [...] Read more.
    In the chemical investigation of marine unicellular bacteria, a new peptide, thalassospiramide G (1), along with thalassospiramides A and D (23), was discovered from a large culture of Thalassospira sp. The structure of thalassospiramide G, bearing γ-amino acids, such as 4-amino-5-hydroxy-penta-2-enoic acid (AHPEA), 4-amino-3,5-dihydroxy-pentanoic acid (ADPA), and unique 2-amino-1-(1H-indol-3-yl) ethanone (AIEN), was determined via extensive spectroscopic analysis. The absolute configuration of thalassospiramide D (3), including 4-amino-3-hydroxy-5-phenylpentanoic acid (AHPPA), was rigorously determined by 1H–1H coupling constant analysis and chemical derivatization. Thalassospiramides A and D (23) inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated mouse macrophage RAW 264.7 cells, with IC50 values of 16.4 and 4.8 μM, respectively. Full article
    (This article belongs to the Special Issue Marine Secondary Metabolites)
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    Open AccessArticle Sources of Secondary Metabolite Variation in Dysidea avara (Porifera: Demospongiae): The Importance of Having Good Neighbors
    Mar. Drugs 2013, 11(2), 489-503; doi:10.3390/md11020489
    Received: 29 November 2012 / Revised: 4 January 2013 / Accepted: 24 January 2013 / Published: 18 February 2013
    Cited by 8 | PDF Full-text (755 KB) | HTML Full-text | XML Full-text | Supplementary Files
    Abstract
    Several studies report temporal, geographical, and intra-individual variation in sponge metabolite yields. However, the internal and/or external factors that regulate the metabolite production remain poorly understood. Dysidea avara is a demosponge that produces sesquiterpenoids (avarol and derivatives) with interesting medical properties, which [...] Read more.
    Several studies report temporal, geographical, and intra-individual variation in sponge metabolite yields. However, the internal and/or external factors that regulate the metabolite production remain poorly understood. Dysidea avara is a demosponge that produces sesquiterpenoids (avarol and derivatives) with interesting medical properties, which has prompted addressed studies to obtain enough amounts of these metabolites for research on drug discovery. Within this framework, specimens of Dysidea avara from a population of the Northwest Mediterranean were sampled and their secondary metabolites quantified to assess their variability and the possible relationship with external (seasonality, interactions with neighbors) and internal (reproductive stages) factors. The results show a variation of the amount of both avarol and its monoacetate derivative with time, with no clear relationship with seawater temperature. A trade-off with sponge reproduction was not found either. However, our results showed for the first time that sponges are able to increase production or accumulation of secondary metabolites in their peripheral zone depending on the nature of their neighbors. This finding could explain part of the high variability in the amount of secondary metabolites usually found in chemical ecology studies on sponges and opens new biotechnological approaches to enhance the metabolite yield in sponge cultures. Full article
    (This article belongs to the Special Issue Marine Secondary Metabolites)
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    Open AccessArticle A Sulfated-Polysaccharide Fraction from Seaweed Gracilaria birdiae Prevents Naproxen-Induced Gastrointestinal Damage in Rats
    Mar. Drugs 2012, 10(12), 2618-2633; doi:10.3390/md10122618
    Received: 26 September 2012 / Revised: 16 October 2012 / Accepted: 18 October 2012 / Published: 22 November 2012
    Cited by 9 | PDF Full-text (596 KB) | HTML Full-text | XML Full-text
    Abstract
    Red seaweeds synthesize a great variety of sulfated galactans. Sulfated polysaccharides (PLSs) from seaweed are comprised of substances with pharmaceutical and biomedical potential. The aim of the present study was to evaluate the protective effect of the PLS fraction extracted from the [...] Read more.
    Red seaweeds synthesize a great variety of sulfated galactans. Sulfated polysaccharides (PLSs) from seaweed are comprised of substances with pharmaceutical and biomedical potential. The aim of the present study was to evaluate the protective effect of the PLS fraction extracted from the seaweed Gracilaria birdiae in rats with naproxen-induced gastrointestinal damage. Male Wistar rats were pretreated with 0.5% carboxymethylcellulose (control group—vehicle) or PLS (10, 30, and 90 mg/kg, p.o.) twice daily (at 09:00 and 21:00) for 2 days. After 1 h, naproxen (80 mg/kg, p.o.) was administered. The rats were killed on day two, 4 h after naproxen treatment. The stomachs were promptly excised, opened along the greater curvature, and measured using digital calipers. Furthermore, the guts of the animals were removed, and a 5-cm portion of the small intestine (jejunum and ileum) was used for the evaluation of macroscopic scores. Samples of the stomach and the small intestine were used for histological evaluation, morphometric analysis and in assays for glutathione (GSH) levels, malonyldialdehyde (MDA) concentration, and myeloperoxidase (MPO) activity. PLS treatment reduced the macroscopic and microscopic naproxen-induced gastrointestinal damage in a dose-dependent manner. Our results suggest that the PLS fraction has a protective effect against gastrointestinal damage through mechanisms that involve the inhibition of inflammatory cell infiltration and lipid peroxidation. Full article
    (This article belongs to the Special Issue Marine Secondary Metabolites)
    Open AccessArticle Further Investigation of the Mediterranean Sponge Axinella polypoides: Isolation of a New Cyclonucleoside and a New Betaine
    Mar. Drugs 2012, 10(11), 2509-2518; doi:10.3390/md10112509
    Received: 12 September 2012 / Revised: 26 October 2012 / Accepted: 30 October 2012 / Published: 9 November 2012
    Cited by 4 | PDF Full-text (496 KB) | HTML Full-text | XML Full-text | Supplementary Files
    Abstract
    An exhaustive exploration into the metabolic content of the Mediterranean sponge Axinella-polypoides resulted in the isolation of the new betaine 5 and the new cyclonucleoside 8. The structures of the new metabolites were elucidated by spectroscopic methods assisted by [...] Read more.
    An exhaustive exploration into the metabolic content of the Mediterranean sponge Axinella-polypoides resulted in the isolation of the new betaine 5 and the new cyclonucleoside 8. The structures of the new metabolites were elucidated by spectroscopic methods assisted by computational methods. The analysis also provided evidence that the sponge does not elaborate pyrrole-imidazole alkaloids (PIAs) but, interestingly, it was shown to contain two already known cyclodipeptides, compounds 9 (verpacamide A) and 10. Full article
    (This article belongs to the Special Issue Marine Secondary Metabolites)

    Review

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    Open AccessReview Marine Indole Alkaloids
    Mar. Drugs 2015, 13(8), 4814-4914; doi:10.3390/md13084814
    Received: 30 June 2015 / Revised: 17 July 2015 / Accepted: 24 July 2015 / Published: 6 August 2015
    Cited by 6 | PDF Full-text (2512 KB) | HTML Full-text | XML Full-text
    Abstract
    Marine indole alkaloids comprise a large and steadily growing group of secondary metabolites. Their diverse biological activities make many compounds of this class attractive starting points for pharmaceutical development. Several marine-derived indoles were found to possess cytotoxic, antineoplastic, antibacterial and antimicrobial activities, [...] Read more.
    Marine indole alkaloids comprise a large and steadily growing group of secondary metabolites. Their diverse biological activities make many compounds of this class attractive starting points for pharmaceutical development. Several marine-derived indoles were found to possess cytotoxic, antineoplastic, antibacterial and antimicrobial activities, in addition to the action on human enzymes and receptors. The newly isolated indole alkaloids of marine origin since the last comprehensive review in 2003 are reported, and biological aspects will be discussed. Full article
    (This article belongs to the Special Issue Marine Secondary Metabolites)
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    Open AccessReview A Brief Review of Bioactive Metabolites Derived from Deep-Sea Fungi
    Mar. Drugs 2015, 13(8), 4594-4616; doi:10.3390/md13084594
    Received: 2 June 2015 / Revised: 11 July 2015 / Accepted: 14 July 2015 / Published: 23 July 2015
    Cited by 5 | PDF Full-text (1021 KB) | HTML Full-text | XML Full-text
    Abstract
    Deep-sea fungi, the fungi that inhabit the sea and the sediment at depths of over 1000 m below the surface, have become an important source of industrial, agricultural, and nutraceutical compounds based on their diversities in both structure and function. Since the [...] Read more.
    Deep-sea fungi, the fungi that inhabit the sea and the sediment at depths of over 1000 m below the surface, have become an important source of industrial, agricultural, and nutraceutical compounds based on their diversities in both structure and function. Since the first study of deep-sea fungi in the Atlantic Ocean at a depth of 4450 m was conducted approximately 50 years ago, hundreds of isolates of deep-sea fungi have been reported based on culture-dependent methods. To date more than 180 bioactive secondary metabolites derived from deep-sea fungi have been documented in the literature. These include compounds with anticancer, antimicrobial, antifungal, antiprotozoal, and antiviral activities. In this review, we summarize the structures and bioactivities of these metabolites to provide help for novel drug development. Full article
    (This article belongs to the Special Issue Marine Secondary Metabolites)
    Open AccessReview Molecular Architecture and Biomedical Leads of Terpenes from Red Sea Marine Invertebrates
    Mar. Drugs 2015, 13(5), 3154-3181; doi:10.3390/md13053154
    Received: 9 April 2015 / Revised: 5 May 2015 / Accepted: 7 May 2015 / Published: 20 May 2015
    Cited by 5 | PDF Full-text (1162 KB) | HTML Full-text | XML Full-text
    Abstract
    Marine invertebrates including sponges, soft coral, tunicates, mollusks and bryozoan have proved to be a prolific source of bioactive natural products. Among marine-derived metabolites, terpenoids have provided a vast array of molecular architectures. These isoprenoid-derived metabolites also exhibit highly specialized biological activities [...] Read more.
    Marine invertebrates including sponges, soft coral, tunicates, mollusks and bryozoan have proved to be a prolific source of bioactive natural products. Among marine-derived metabolites, terpenoids have provided a vast array of molecular architectures. These isoprenoid-derived metabolites also exhibit highly specialized biological activities ranging from nerve regeneration to blood-sugar regulation. As a result, intense research activity has been devoted to characterizing invertebrate terpenes from both a chemical and biological standpoint. This review focuses on the chemistry and biology of terpene metabolites isolated from the Red Sea ecosystem, a unique marine biome with one of the highest levels of biodiversity and specifically rich in invertebrate species. Full article
    (This article belongs to the Special Issue Marine Secondary Metabolites)
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    Open AccessReview Bioactive Compounds from Macroalgae in the New Millennium: Implications for Neurodegenerative Diseases
    Mar. Drugs 2014, 12(9), 4934-4972; doi:10.3390/md12094934
    Received: 18 June 2014 / Revised: 5 September 2014 / Accepted: 15 September 2014 / Published: 25 September 2014
    Cited by 11 | PDF Full-text (1994 KB) | HTML Full-text | XML Full-text
    Abstract
    Marine environment has proven to be a rich source of structurally diverse and complex compounds exhibiting numerous interesting biological effects. Macroalgae are currently being explored as novel and sustainable sources of bioactive compounds for both pharmaceutical and nutraceutical applications. Given the increasing [...] Read more.
    Marine environment has proven to be a rich source of structurally diverse and complex compounds exhibiting numerous interesting biological effects. Macroalgae are currently being explored as novel and sustainable sources of bioactive compounds for both pharmaceutical and nutraceutical applications. Given the increasing prevalence of different forms of dementia, researchers have been focusing their attention on the discovery and development of new compounds from macroalgae for potential application in neuroprotection. Neuroprotection involves multiple and complex mechanisms, which are deeply related. Therefore, compounds exerting neuroprotective effects through different pathways could present viable approaches in the management of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s. In fact, several studies had already provided promising insights into the neuroprotective effects of a series of compounds isolated from different macroalgae species. This review will focus on compounds from macroalgae that exhibit neuroprotective effects and their potential application to treat and/or prevent neurodegenerative diseases. Full article
    (This article belongs to the Special Issue Marine Secondary Metabolites)
    Open AccessReview Diversity of Secondary Metabolites from Marine Bacillus Species: Chemistry and Biological Activity
    Mar. Drugs 2013, 11(8), 2846-2872; doi:10.3390/md11082846
    Received: 1 May 2013 / Revised: 12 July 2013 / Accepted: 29 July 2013 / Published: 12 August 2013
    Cited by 18 | PDF Full-text (918 KB) | HTML Full-text | XML Full-text
    Abstract
    Marine Bacillus species produce versatile secondary metabolites including lipopeptides, polypeptides, macrolactones, fatty acids, polyketides, and isocoumarins. These structurally diverse compounds exhibit a wide range of biological activities, such as antimicrobial, anticancer, and antialgal activities. Some marine Bacillus strains can detoxify heavy metals [...] Read more.
    Marine Bacillus species produce versatile secondary metabolites including lipopeptides, polypeptides, macrolactones, fatty acids, polyketides, and isocoumarins. These structurally diverse compounds exhibit a wide range of biological activities, such as antimicrobial, anticancer, and antialgal activities. Some marine Bacillus strains can detoxify heavy metals through reduction processes and have the ability to produce carotenoids. The present article reviews the chemistry and biological activities of secondary metabolites from marine isolates. Side by side, the potential for application of these novel natural products from marine Bacillus strains as drugs, pesticides, carotenoids, and tools for the bioremediation of heavy metal toxicity are also discussed. Full article
    (This article belongs to the Special Issue Marine Secondary Metabolites)
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    Open AccessReview Meroterpenes from Marine Invertebrates: Structures, Occurrence, and Ecological Implications
    Mar. Drugs 2013, 11(5), 1602-1643; doi:10.3390/md11051602
    Received: 19 March 2013 / Revised: 7 April 2013 / Accepted: 7 May 2013 / Published: 17 May 2013
    Cited by 14 | PDF Full-text (3645 KB) | HTML Full-text | XML Full-text
    Abstract
    Meroterpenes are widely distributed among marine organisms; they are particularly abundant within brown algae, but other important sources include microorganisms and invertebrates. In the present review the structures and bioactivities of meroterpenes from marine invertebrates, mainly sponges and tunicates, are summarized. More [...] Read more.
    Meroterpenes are widely distributed among marine organisms; they are particularly abundant within brown algae, but other important sources include microorganisms and invertebrates. In the present review the structures and bioactivities of meroterpenes from marine invertebrates, mainly sponges and tunicates, are summarized. More than 300 molecules, often complex and with unique skeletons originating from intra- and inter-molecular cyclizations, and/or rearrangements, are illustrated. The reported syntheses are mentioned. The issue of a potential microbial link to their biosynthesis is also shortly outlined. Full article
    (This article belongs to the Special Issue Marine Secondary Metabolites)
    Open AccessReview Recent Advances in the Discovery and Development of Marine Microbial Natural Products
    Mar. Drugs 2013, 11(3), 700-717; doi:10.3390/md11030700
    Received: 28 December 2012 / Revised: 25 January 2013 / Accepted: 6 February 2013 / Published: 8 March 2013
    Cited by 37 | PDF Full-text (652 KB) | HTML Full-text | XML Full-text
    Abstract
    Marine microbial natural products (MMNPs) have attracted increasing attention from microbiologists, taxonomists, ecologists, agronomists, chemists and evolutionary biologists during the last few decades. Numerous studies have indicated that diverse marine microbes appear to have the capacity to produce an impressive array of [...] Read more.
    Marine microbial natural products (MMNPs) have attracted increasing attention from microbiologists, taxonomists, ecologists, agronomists, chemists and evolutionary biologists during the last few decades. Numerous studies have indicated that diverse marine microbes appear to have the capacity to produce an impressive array of MMNPs exhibiting a wide variety of biological activities such as antimicrobial, anti-tumor, anti-inflammatory and anti-cardiovascular agents. Marine microorganisms represent an underexplored reservoir for the discovery of MMNPs with unique scaffolds and for exploitation in the pharmaceutical and agricultural industries. This review focuses on MMNPs discovery and development over the past decades, including innovative isolation and culture methods, strategies for discovering novel MMNPs via routine screenings, metagenomics, genomics, combinatorial biosynthesis, and synthetic biology. The potential problems and future directions for exploring MMNPs are also discussed. Full article
    (This article belongs to the Special Issue Marine Secondary Metabolites)

    Other

    Jump to: Research, Review

    Open AccessShort Note Probing a Coral Genome for Components of the Photoprotective Scytonemin Biosynthetic Pathway and the 2-Aminoethylphosphonate Pathway
    Mar. Drugs 2013, 11(2), 559-570; doi:10.3390/md11020559
    Received: 9 January 2013 / Revised: 1 February 2013 / Accepted: 6 February 2013 / Published: 22 February 2013
    Cited by 1 | PDF Full-text (565 KB) | HTML Full-text | XML Full-text | Supplementary Files
    Abstract
    Genome sequences of the reef-building coral, Acropora digitifera, have been decoded. Acropora inhabits an environment with intense ultraviolet exposure and hosts the photosynthetic endosymbiont, Symbiodinium. Acropora homologs of all four genes necessary for biosynthesis of the photoprotective cyanobacterial compound, shinorine, [...] Read more.
    Genome sequences of the reef-building coral, Acropora digitifera, have been decoded. Acropora inhabits an environment with intense ultraviolet exposure and hosts the photosynthetic endosymbiont, Symbiodinium. Acropora homologs of all four genes necessary for biosynthesis of the photoprotective cyanobacterial compound, shinorine, are present. Among metazoans, these genes are found only in anthozoans. To gain further evolutionary insights into biosynthesis of photoprotective compounds and associated coral proteins, we surveyed the Acropora genome for 18 clustered genes involved in cyanobacterial synthesis of the anti-UV compound, scytonemin, even though it had not previously been detected in corals. We identified candidates for only 6 of the 18 genes, including tyrP, scyA, and scyB. Therefore, it does not appear that Acropora digitifera can synthesize scytonemin independently. On the other hand, molecular phylogenetic analysis showed that one tyrosinase gene is an ortholog of vertebrate tyrosinase genes and that the coral homologs, scyA and scyB, are similar to bacterial metabolic genes, phosphonopyruvate (ppyr) decarboxylase and glutamate dehydrogenase (GDH), respectively. Further genomic searches for ppyr gene-related biosynthetic components indicate that the coral possesses a metabolic pathway similar to the bacterial 2-aminoethylphosphonate (AEP) biosynthetic pathway. The results suggest that de novo synthesis of carbon-phosphorus compounds is performed in corals. Full article
    (This article belongs to the Special Issue Marine Secondary Metabolites)

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