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Special Issue "Marine Bioactive Natural Product Studies—A Southern Hemisphere Perspective"

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

Deadline for manuscript submissions: closed (31 July 2015)

Special Issue Editor

Guest Editor
Dr. Sylvia Urban

School of Applied Sciences (Applied Chemistry), RMIT University (City Campus), GPO Box 2476V, Melbourne 3001, Victoria, Australia
Website1 | Website2 | Website3 | E-Mail
Phone: +61 3 9925 3376
Fax: +61 3 9925 3747
Interests: marine and terrestrial natural products chemistry; isolation and structural characterization; NMR spectroscopy; analytical separation methodologies

Special Issue Information

Dear Colleagues,

The search for bioactive secondary metabolites from marine organisms has been an active area of research since the 1950s. The distinct biodiversity of the marine environment has afforded a vast array of unique secondary metabolites, many of which possess potent biological activities. This special issue of Marine Drugs will highlight recent bioactive marine natural product studies conducted by southern hemisphere scientists on an array of marine organisms.

Dr. Sylvia Urban
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 natural products
  • bioactivity
  • biodiscovery
  • hyphenated technologies
  • marine algae
  • marine sponges
  • marine acidians
  • other marine invertebrates
  • extraction methodologies

Published Papers (9 papers)

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Research

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Open AccessArticle Salternamide A Suppresses Hypoxia-Induced Accumulation of HIF-1α and Induces Apoptosis in Human Colorectal Cancer Cells
Mar. Drugs 2015, 13(11), 6962-6976; doi:10.3390/md13116962
Received: 28 August 2015 / Accepted: 12 November 2015 / Published: 19 November 2015
Cited by 2 | PDF Full-text (1774 KB) | HTML Full-text | XML Full-text
Abstract
Hypoxia inducible factor-1α (HIF-1α) is an essential regulator of the cellular response to low oxygen concentrations, activating a broad range of genes that provide adaptive responses to oxygen deprivation. HIF-1α is overexpressed in various cancers and therefore represents a considerable chemotherapeutic target. Salternamide
[...] Read more.
Hypoxia inducible factor-1α (HIF-1α) is an essential regulator of the cellular response to low oxygen concentrations, activating a broad range of genes that provide adaptive responses to oxygen deprivation. HIF-1α is overexpressed in various cancers and therefore represents a considerable chemotherapeutic target. Salternamide A (SA), a novel small molecule that is isolated from a halophilic Streptomyces sp., is a potent cytotoxic agent against a variety of human cancer cell lines. However, the mechanisms by which SA inhibits tumor growth remain to be elucidated. In the present study, we demonstrate that SA efficiently inhibits the hypoxia-induced accumulation of HIF-1α in a time- and concentration-dependent manner in various human cancer cells. In addition, SA suppresses the upstream signaling of HIF-1α, such as PI3K/Akt/mTOR, p42/p44 MAPK, and STAT3 signaling under hypoxic conditions. Furthermore, we found that SA induces cell death by stimulating G2/M cell cycle arrest and apoptosis in human colorectal cancer cells. Taken together, SA was identified as a novel small molecule HIF-1α inhibitor from marine natural products and is potentially a leading candidate in the development of anticancer agents. Full article
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Open AccessArticle Synthesis and Antiplasmodial Evaluation of Analogues Based on the Tricyclic Core of Thiaplakortones A–D
Mar. Drugs 2015, 13(9), 5784-5795; doi:10.3390/md13095784
Received: 14 August 2015 / Revised: 4 September 2015 / Accepted: 7 September 2015 / Published: 15 September 2015
Cited by 1 | PDF Full-text (271 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Six regioisomers associated with the tricyclic core of thiaplakortones A–D have been synthesized. Reaction of 1H-indole-4,7-dione and 1-tosyl-1H-indole-4,7-dione with 2-aminoethanesulfinic acid afforded a regioisomeric series, which was subsequently deprotected and oxidized to yield the tricyclic core scaffolds present in
[...] Read more.
Six regioisomers associated with the tricyclic core of thiaplakortones A–D have been synthesized. Reaction of 1H-indole-4,7-dione and 1-tosyl-1H-indole-4,7-dione with 2-aminoethanesulfinic acid afforded a regioisomeric series, which was subsequently deprotected and oxidized to yield the tricyclic core scaffolds present in the thiaplakortones. All compounds were fully characterized using NMR and MS data. A single crystal X-ray structure was obtained on one of the N-tosyl derivatives. All compounds were screened for in vitro antiplasmodial activity against chloroquine-sensitive (3D7) and multidrug-resistant (Dd2) Plasmodium falciparum parasite lines. Several analogues displayed potent inhibition of P. falciparum growth (IC50 < 500 nM) but only moderate selectivity for P. falciparum versus human neonatal foreskin fibroblast cells. Full article
Open AccessArticle Structure-Activity Relationships of the Bioactive Thiazinoquinone Marine Natural Products Thiaplidiaquinones A and B
Mar. Drugs 2015, 13(8), 5102-5110; doi:10.3390/md13085102
Received: 15 July 2015 / Accepted: 4 August 2015 / Published: 10 August 2015
PDF Full-text (640 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In an effort to more accurately define the mechanism of cell death and to establish structure-activity relationship requirements for the marine meroterpenoid alkaloids thiaplidiaquinones A and B, we have evaluated not only the natural products but also dioxothiazine regioisomers and two precursor quinones
[...] Read more.
In an effort to more accurately define the mechanism of cell death and to establish structure-activity relationship requirements for the marine meroterpenoid alkaloids thiaplidiaquinones A and B, we have evaluated not only the natural products but also dioxothiazine regioisomers and two precursor quinones in a range of bioassays. While the natural products were found to be weak inducers of ROS in Jurkat cells, the dioxothiazine regioisomer of thiaplidiaquinone A and a synthetic precursor to thiaplidiaquinone B were found to be moderately potent inducers. Intriguingly, and in contrast to previous reports, the mechanism of Jurkat cell death (necrosis vs. apoptosis) was found to be dependent upon the positioning of one of the geranyl sidechains in the compounds with thiaplidiaquinone A and its dioxothiazine regioisomer causing death dominantly by necrosis, while thiaplidiaquinone B and its dioxothiazine isomer caused cell death via apoptosis. The dioxothiazine regioisomer of thiaplidiaquinone A exhibited more potent in vitro antiproliferative activity against human tumor cells, with NCI sub-panel selectivity towards melanoma cell lines. The non-natural dioxothiazine regioisomers were also more active in antiplasmodial and anti-farnesyltransferase assays than their natural product counterparts. The results highlight the important role that natural product total synthesis can play in not only helping understand the structural basis of biological activity of natural products, but also the discovery of new bioactive scaffolds. Full article
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Open AccessArticle Isolation and Total Synthesis of Stolonines A–C, Unique Taurine Amides from the Australian Marine Tunicate Cnemidocarpa stolonifera
Mar. Drugs 2015, 13(7), 4556-4575; doi:10.3390/md13074556
Received: 19 June 2015 / Revised: 12 July 2015 / Accepted: 14 July 2015 / Published: 22 July 2015
Cited by 1 | PDF Full-text (3059 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Cnemidocarpa stolonifera is an underexplored marine tunicate that only occurs on the tropical to subtropical East Coast of Australia, with only two pyridoacridine compounds reported previously. Qualitative analysis of the lead-like enhanced fractions of C. stolonifera by LC-MS dual electrospray ionization coupled with
[...] Read more.
Cnemidocarpa stolonifera is an underexplored marine tunicate that only occurs on the tropical to subtropical East Coast of Australia, with only two pyridoacridine compounds reported previously. Qualitative analysis of the lead-like enhanced fractions of C. stolonifera by LC-MS dual electrospray ionization coupled with PDA and ELSD detectors led to the identification of three new natural products, stolonines A–C (13), belonging to the taurine amide structure class. Structures of the new compounds were determined by NMR and MS analyses and later verified by total synthesis. This is the first time that the conjugates of taurine with 3-indoleglyoxylic acid, quinoline-2-carboxylic acid and β-carboline-3-carboxylic acid present in stolonines A–C (13), respectively, have been reported. An immunofluorescence assay on PC3 cells indicated that compounds 1 and 3 increased cell size, induced mitochondrial texture elongation, and caused apoptosis in PC3 cells. Full article
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Open AccessArticle Structure Elucidation of New Acetylated Saponins, Lessoniosides A, B, C, D, and E, and Non-Acetylated Saponins, Lessoniosides F and G, from the Viscera of the Sea Cucumber Holothuria lessoni
Mar. Drugs 2015, 13(1), 597-617; doi:10.3390/md13010597
Received: 8 August 2014 / Accepted: 1 January 2015 / Published: 16 January 2015
Cited by 2 | PDF Full-text (1473 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Sea cucumbers produce numerous compounds with a wide range of chemical structural diversity. Among these, saponins are the most diverse and include sulfated, non-sulfated, acetylated and methylated congeners with different aglycone and sugar moieties. In this study, MALDI and ESI tandem mass spectrometry,
[...] Read more.
Sea cucumbers produce numerous compounds with a wide range of chemical structural diversity. Among these, saponins are the most diverse and include sulfated, non-sulfated, acetylated and methylated congeners with different aglycone and sugar moieties. In this study, MALDI and ESI tandem mass spectrometry, in the positive ion mode, were used to elucidate the structure of new saponins extracted from the viscera of H. lessoni. Fragmentation of the aglycone provided structural information on the presence of the acetyl group. The presence of the O-acetyl group was confirmed by observing the mass transition of 60 u corresponding to the loss of a molecule of acetic acid. Ion fingerprints from the glycosidic cleavage provided information on the mass of the aglycone (core), and the sequence and type of monosaccharides that constitute the sugar moiety. The tandem mass spectra of the saponin precursor ions [M + Na]+ provided a wealth of detailed structural information on the glycosidic bond cleavages. As a result, and in conjunction with existing literature, we characterized the structure of five new acetylated saponins, Lessoniosides A–E, along with two non-acetylated saponins Lessoniosides F and G at m/z 1477.7, which are promising candidates for future drug development. The presented strategy allows a rapid, reliable and complete analysis of native saponins. Full article
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Open AccessArticle A Great Barrier Reef Sinularia sp. Yields Two New Cytotoxic Diterpenes
Mar. Drugs 2012, 10(8), 1619-1630; doi:10.3390/md10081619
Received: 4 June 2012 / Revised: 25 June 2012 / Accepted: 23 July 2012 / Published: 31 July 2012
Cited by 9 | PDF Full-text (327 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The methanol extract of a Sinularia sp., collected from Bowden Reef, Queensland, Australia, yielded ten natural products. These included the new nitrogenous diterpene (4R*,5R*,9S*,10R*,11Z)-4-methoxy-9-((dimethylamino)-methyl)-12,15-epoxy-11(13)-en-decahydronaphthalen-16-ol (1), and the new lobane, (1R*
[...] Read more.
The methanol extract of a Sinularia sp., collected from Bowden Reef, Queensland, Australia, yielded ten natural products. These included the new nitrogenous diterpene (4R*,5R*,9S*,10R*,11Z)-4-methoxy-9-((dimethylamino)-methyl)-12,15-epoxy-11(13)-en-decahydronaphthalen-16-ol (1), and the new lobane, (1R*,2R*,4S*,15E)-loba-8,10,13(14),15(16)-tetraen-17,18-diol-17-acetate (2). Also isolated were two known cembranes, sarcophytol-B and (1E,3E,7E)-11,12-epoxycembratrien-15-ol, and six known lobanes, loba-8,10,13(15)-triene-16,17,18-triol, 14,18-epoxyloba-8,10,13(15)-trien-17-ol, lobatrientriol, lobatrienolide, 14,17-epoxyloba-8,10,13(15)-trien-18-ol-18-acetate and (17R)-loba-8,10,13(15)-trien-17,18-diol. Structures of the new compounds were elucidated through interpretation of spectra obtained after extensive NMR and MS investigations and comparison with literature values. The tumour cell growth inhibition potential of 1 and 2 along with loba-8,10,13(15)-triene-16,17,18-triol, 14,17-epoxyloba-8,10,13(15)-trien-18-ol-18-acetate, lobatrienolide, (1E,3E,7E)-11,12-epoxycembratrien-15-ol and sarcophytol-B were assessed against three human tumour cell lines (SF-268, MCF-7 and H460). The lobanes and cembranes tested demonstrated 50% growth inhibition in the range 6.8–18.5 µM, with no selectivity, whilst 1 was less active (GI50 70–175 µM). Full article
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Review

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Open AccessReview Recent Advances in Drug Discovery from South African Marine Invertebrates
Mar. Drugs 2015, 13(10), 6366-6383; doi:10.3390/md13106366
Received: 25 July 2015 / Revised: 28 September 2015 / Accepted: 29 September 2015 / Published: 14 October 2015
Cited by 1 | PDF Full-text (2273 KB) | HTML Full-text | XML Full-text
Abstract
Recent developments in marine drug discovery from three South African marine invertebrates, the tube worm Cephalodiscus gilchristi, the ascidian Lissoclinum sp. and the sponge Topsentia pachastrelloides, are presented. Recent reports of the bioactivity and synthesis of the anti-cancer secondary metabolites cephalostatin
[...] Read more.
Recent developments in marine drug discovery from three South African marine invertebrates, the tube worm Cephalodiscus gilchristi, the ascidian Lissoclinum sp. and the sponge Topsentia pachastrelloides, are presented. Recent reports of the bioactivity and synthesis of the anti-cancer secondary metabolites cephalostatin and mandelalides (from C. gilchristi and Lissoclinum sp., respectively) and various analogues are presented. The threat of drug-resistant pathogens, e.g., methicillin-resistant Staphylococcus aureus (MRSA), is assuming greater global significance, and medicinal chemistry strategies to exploit the potent MRSA PK inhibition, first revealed by two marine secondary metabolites, cis-3,4-dihydrohamacanthin B and bromodeoxytopsentin from T. pachastrelloides, are compared. Full article
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Open AccessReview Natural Product Research in the Australian Marine Invertebrate Dicathais orbita
Mar. Drugs 2013, 11(4), 1370-1398; doi:10.3390/md11041370
Received: 14 January 2013 / Revised: 4 March 2013 / Accepted: 8 March 2013 / Published: 23 April 2013
Cited by 20 | PDF Full-text (777 KB) | HTML Full-text | XML Full-text
Abstract
The predatory marine gastropod Dicathais orbita has been the subject of a significant amount of biological and chemical research over the past five decades. Natural products research on D. orbita includes the isolation and identification of brominated indoles and choline esters as precursors
[...] Read more.
The predatory marine gastropod Dicathais orbita has been the subject of a significant amount of biological and chemical research over the past five decades. Natural products research on D. orbita includes the isolation and identification of brominated indoles and choline esters as precursors of Tyrian purple, as well as the synthesis of structural analogues, bioactivity testing, biodistributional and biosynthetic studies. Here I also report on how well these compounds conform to Lipinski’s rule of five for druglikeness and their predicted receptor binding and enzyme inhibitor activity. The composition of mycosporine-like amino acids, fatty acids and sterols has also been described in the egg masses of D. orbita. The combination of bioactive compounds produced by D. orbita is of interest for further studies in chemical ecology, as well as for future nutraceutical development. Biological insights into the life history of this species, as well as ongoing research on the gene expression, microbial symbionts and biosynthetic capabilities, should facilitate sustainable production of the bioactive compounds. Knowledge of the phylogeny of D. orbita provides an excellent platform for novel research into the evolution of brominated secondary metabolites in marine molluscs. The range of polarities in the brominated indoles produced by D. orbita has also provided an effective model system used to develop a new method for biodistributional studies. The well characterized suite of chemical reactions that generate Tyrian purple, coupled with an in depth knowledge of the ecology, anatomy and genetics of D. orbita provide a good foundation for ongoing natural products research. Full article
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Open AccessReview Computational Studies of Marine Toxins Targeting Ion Channels
Mar. Drugs 2013, 11(3), 848-869; doi:10.3390/md11030848
Received: 19 December 2012 / Revised: 30 January 2013 / Accepted: 7 February 2013 / Published: 13 March 2013
Cited by 11 | PDF Full-text (1632 KB) | HTML Full-text | XML Full-text
Abstract
Toxins from marine animals offer novel drug leads for treatment of diseases involving ion channels. Computational methods could be very helpful in this endeavour in several ways, e.g., (i) constructing accurate models of the channel-toxin complexes using docking and molecular dynamics (MD) simulations;
[...] Read more.
Toxins from marine animals offer novel drug leads for treatment of diseases involving ion channels. Computational methods could be very helpful in this endeavour in several ways, e.g., (i) constructing accurate models of the channel-toxin complexes using docking and molecular dynamics (MD) simulations; (ii) determining the binding free energies of toxins from umbrella sampling MD simulations; (iii) predicting the effect of mutations from free energy MD simulations. Using these methods, one can design new analogs of toxins with improved affinity and selectivity properties. Here we present a review of the computational methods and discuss their applications to marine toxins targeting potassium and sodium channels. Detailed examples from the potassium channel toxins—ShK from sea anemone and κ-conotoxin PVIIA—are provided to demonstrate capabilities of the computational methods to give accurate descriptions of the channel-toxin complexes and the energetics of their binding. An example is also given from sodium channel toxins (μ-conotoxin GIIIA) to illustrate the differences between the toxin binding modes in potassium and sodium channels. Full article

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