Next Issue
Previous Issue

E-Mail Alert

Add your e-mail address to receive forthcoming issues of this journal:

Journal Browser

Journal Browser

Table of Contents

Mar. Drugs, Volume 10, Issue 6 (June 2012), Pages 1192-1421

  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Readerexternal link to open them.
View options order results:
result details:
Displaying articles 1-17
Export citation of selected articles as:

Research

Jump to: Review

Open AccessArticle Diversity of Nonribosomal Peptide Synthetase Genes in the Microbial Metagenomes of Marine Sponges
Mar. Drugs 2012, 10(6), 1192-1202; doi:10.3390/md10061192
Received: 23 April 2012 / Revised: 18 May 2012 / Accepted: 21 May 2012 / Published: 25 May 2012
Cited by 8 | PDF Full-text (682 KB) | HTML Full-text | XML Full-text
Abstract
Genomic mining revealed one major nonribosomal peptide synthetase (NRPS) phylogenetic cluster in 12 marine sponge species, one ascidian, an actinobacterial isolate and seawater. Phylogenetic analysis predicts its taxonomic affiliation to the actinomycetes and hydroxy-phenyl-glycine as a likely substrate. Additionally, a phylogenetically distinct [...] Read more.
Genomic mining revealed one major nonribosomal peptide synthetase (NRPS) phylogenetic cluster in 12 marine sponge species, one ascidian, an actinobacterial isolate and seawater. Phylogenetic analysis predicts its taxonomic affiliation to the actinomycetes and hydroxy-phenyl-glycine as a likely substrate. Additionally, a phylogenetically distinct NRPS gene cluster was discovered in the microbial metagenome of the sponge Aplysina aerophoba, which shows highest similarities to NRPS genes that were previously assigned, by ways of single cell genomics, to a Chloroflexi sponge symbiont. Genomic mining studies such as the one presented here for NRPS genes, contribute to on-going efforts to characterize the genomic potential of sponge-associated microbiota for secondary metabolite biosynthesis. Full article
(This article belongs to the Special Issue Metagenomics in Biodiscovery from Oceans)
Open AccessArticle Simplexins P–S, Eunicellin-Based Diterpenes from the Soft Coral Klyxum simplex
Mar. Drugs 2012, 10(6), 1203-1211; doi:10.3390/md10061203
Received: 27 April 2012 / Revised: 18 May 2012 / Accepted: 22 May 2012 / Published: 25 May 2012
Cited by 8 | PDF Full-text (389 KB) | HTML Full-text | XML Full-text | Correction | Supplementary Files
Abstract
Four new eunicellin-based diterpenes, simplexins P–S (14), and the known compound simplexin A (5), have been isolated from the soft coral Klyxum simplex. The structures of the new metabolites were determined on the basis of [...] Read more.
Four new eunicellin-based diterpenes, simplexins P–S (14), and the known compound simplexin A (5), have been isolated from the soft coral Klyxum simplex. The structures of the new metabolites were determined on the basis of extensive spectroscopic analysis, particularly 1D and 2D NMR experiments. Compounds 1 and 35 were shown to exhibit cytotoxicity against a limited panel of cancer cell lines, 3 being the most cytotoxic. Full article
Open AccessArticle Mycalamide A Shows Cytotoxic Properties and Prevents EGF-Induced Neoplastic Transformation through Inhibition of Nuclear Factors
Mar. Drugs 2012, 10(6), 1212-1224; doi:10.3390/md10061212
Received: 31 March 2012 / Revised: 15 May 2012 / Accepted: 21 May 2012 / Published: 30 May 2012
Cited by 19 | PDF Full-text (710 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Mycalamide A, a marine natural compound previously isolated from sponges, is known as a protein synthesis inhibitor with potent antitumor activity. However, the ability of this compound to prevent malignant transformation of cells has never been examined before. Here, for the first [...] Read more.
Mycalamide A, a marine natural compound previously isolated from sponges, is known as a protein synthesis inhibitor with potent antitumor activity. However, the ability of this compound to prevent malignant transformation of cells has never been examined before. Here, for the first time, we report the isolation of mycalamide A from ascidian Polysincraton sp. as well as investigation of its cancer preventive properties. In murine JB6 Cl41 P+ cells, mycalamide A inhibited epidermal growth factor (EGF)-induced neoplastic transformation, and induced apoptosis at subnanomolar or nanomolar concentrations. The compound inhibited transcriptional activity of the oncogenic nuclear factors AP-1 and NF-κB, a potential mechanism of its cancer preventive properties. Induction of phosphorylation of the kinases MAPK p38, JNK, and ERK was also observed at high concentrations of mycalamide A. The drug shows promising potential for both cancer-prevention and cytotoxic therapy and should be further developed. Full article
Figures

Open AccessArticle Microbial Regulation in Gorgonian Corals
Mar. Drugs 2012, 10(6), 1225-1243; doi:10.3390/md10061225
Received: 5 April 2012 / Revised: 21 May 2012 / Accepted: 28 May 2012 / Published: 4 June 2012
Cited by 11 | PDF Full-text (365 KB) | HTML Full-text | XML Full-text
Abstract
Gorgonian corals possess many novel natural products that could potentially mediate coral-bacterial interactions. Since many bacteria use quorum sensing (QS) signals to facilitate colonization of host organisms, regulation of prokaryotic cell-to-cell communication may represent an important bacterial control mechanism. In the present [...] Read more.
Gorgonian corals possess many novel natural products that could potentially mediate coral-bacterial interactions. Since many bacteria use quorum sensing (QS) signals to facilitate colonization of host organisms, regulation of prokaryotic cell-to-cell communication may represent an important bacterial control mechanism. In the present study, we examined extracts of twelve species of Caribbean gorgonian corals, for mechanisms that regulate microbial colonization, such as antibacterial activity and QS regulatory activity. Ethanol extracts of gorgonians collected from Puerto Rico and the Florida Keys showed a range of both antibacterial and QS activities using a specific Pseudomonas aeruginosa QS reporter, sensitive to long chain AHLs and a short chain N-acylhomoserine lactones (AHL) biosensor, Chromobacterium violaceium. Overall, the gorgonian corals had higher antimicrobial activity against non-marine strains when compared to marine strains. Pseudopterogorgia americana, Pseusopterogorgia acerosa, and Pseudoplexuara flexuosa had the highest QS inhibitory effect. Interestingly, Pseudoplexuara porosa extracts stimulated QS activity with a striking 17-fold increase in signal. The stimulation of QS by P. porosa or other elements of the holobiont may encourage colonization or recruitment of specific microbial species. Overall, these results suggest the presence of novel stimulatory QS, inhibitory QS and bactericidal compounds in gorgonian corals. A better understanding of these compounds may reveal insight into coral-microbial ecology and whether a therapeutic potential exists. Full article
(This article belongs to the Special Issue Marine Antibiotics)
Figures

Open AccessArticle Purpurogemutantin and Purpurogemutantidin, New Drimenyl Cyclohexenone Derivatives Produced by a Mutant Obtained by Diethyl Sulfate Mutagenesis of a Marine-Derived Penicillium purpurogenum G59
Mar. Drugs 2012, 10(6), 1266-1287; doi:10.3390/md10061266
Received: 9 March 2012 / Revised: 24 May 2012 / Accepted: 24 May 2012 / Published: 4 June 2012
Cited by 24 | PDF Full-text (962 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two new drimenyl cyclohexenone derivatives, named purpurogemutantin (1) and purpurogemutantidin (2), and the known macrophorin A (3) were isolated from a bioactive mutant BD-1-6 obtained by random diethyl sulfate (DES) mutagenesis of a marine-derived Penicillium purpurogenum [...] Read more.
Two new drimenyl cyclohexenone derivatives, named purpurogemutantin (1) and purpurogemutantidin (2), and the known macrophorin A (3) were isolated from a bioactive mutant BD-1-6 obtained by random diethyl sulfate (DES) mutagenesis of a marine-derived Penicillium purpurogenum G59. Structures and absolute configurations of 1 and 2 were determined by extensive spectroscopic methods, especially 2D NMR and electronic circular dichroism (ECD) analysis. Possible biosynthetic pathways for 13 were also proposed and discussed. Compounds 1 and 2 significantly inhibited human cancer K562, HL-60, HeLa, BGC-823 and MCF-7 cells, and compound 3 also inhibited the K562 and HL-60 cells. Both bioassay and chemical analysis (HPLC, LC-ESIMS) demonstrated that the parent strain G59 did not produce 13, and that DES-induced mutation(s) in the mutant BD-1-6 activated some silent biosynthetic pathways in the parent strain G59, including one set for 13 production. Full article
Figures

Open AccessArticle New 19-Oxygenated Steroids from the Soft Coral Nephthea chabrolii
Mar. Drugs 2012, 10(6), 1288-1296; doi:10.3390/md10061288
Received: 3 May 2012 / Revised: 30 May 2012 / Accepted: 30 May 2012 / Published: 6 June 2012
Cited by 8 | PDF Full-text (535 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In order to search for novel bioactive substances from marine organisms, we investigated the acetone extract of the soft coral Nephthea chabrolii collected at San-Hsian-Tai, Taitong County, Taiwan. From this extract three new 19-oxygenated steroids, nebrosteroids N–P (13) [...] Read more.
In order to search for novel bioactive substances from marine organisms, we investigated the acetone extract of the soft coral Nephthea chabrolii collected at San-Hsian-Tai, Taitong County, Taiwan. From this extract three new 19-oxygenated steroids, nebrosteroids N–P (13) were isolated. The structures of these compounds were elucidated by extensive spectroscopic analyses. Full article
Open AccessArticle Quinazolin-4-one Coupled with Pyrrolidin-2-iminium Alkaloids from Marine-Derived Fungus Penicillium aurantiogriseum
Mar. Drugs 2012, 10(6), 1297-1306; doi:10.3390/md10061297
Received: 9 April 2012 / Revised: 29 May 2012 / Accepted: 29 May 2012 / Published: 7 June 2012
Cited by 12 | PDF Full-text (263 KB) | HTML Full-text | XML Full-text
Abstract
Three new alkaloids, including auranomides A and B (1 and 2), a new scaffold containing quinazolin-4-one substituted with a pyrrolidin-2-iminium moiety, and auranomide C (3), as well as two known metabolites auranthine (4) and aurantiomides C [...] Read more.
Three new alkaloids, including auranomides A and B (1 and 2), a new scaffold containing quinazolin-4-one substituted with a pyrrolidin-2-iminium moiety, and auranomide C (3), as well as two known metabolites auranthine (4) and aurantiomides C (5) were isolated from the marine-derived fungus Penicillium aurantiogriseum. The chemical structures of compounds 13 were elucidated by extensive spectroscopic methods, including IR, HRESIMS and 2D NMR spectroscopic analysis. The absolute configurations of compounds 13 were suggested from the perspective of a plausible biosynthesis pathway. Compounds 13 were subjected to antitumor and antimicrobial screening models. Auranomides A–C exhibited moderate cytotoxic activity against human tumor cells. Auranomides B was the most potent among them with an IC50 value of 0.097 μmol/mL against HEPG2 cells. Full article
Open AccessArticle Marine Cyclotripeptide X-13 Promotes Angiogenesis in Zebrafish and Human Endothelial Cells via PI3K/Akt/eNOS Signaling Pathways
Mar. Drugs 2012, 10(6), 1307-1320; doi:10.3390/md10061307
Received: 4 March 2012 / Revised: 8 May 2012 / Accepted: 29 May 2012 / Published: 7 June 2012
Cited by 7 | PDF Full-text (1572 KB) | HTML Full-text | XML Full-text
Abstract
Cyclotripeptide X-13 is a core of novel marine compound xyloallenoide A isolated from mangrove fungus Xylaria sp. (no. 2508). We found that X-13 dose-dependently induced angiogenesis in zebrafish embryos and in human endothelial cells, which was accompanied by increased phosphorylation of eNOS [...] Read more.
Cyclotripeptide X-13 is a core of novel marine compound xyloallenoide A isolated from mangrove fungus Xylaria sp. (no. 2508). We found that X-13 dose-dependently induced angiogenesis in zebrafish embryos and in human endothelial cells, which was accompanied by increased phosphorylation of eNOS and Akt and NO release. Inhibition of PI3K/Akt/eNOS by LY294002 or l-NAME suppressed X-13-induced angiogenesis. The present work demonstrates that X-13 promotes angiogenesis via PI3K/Akt/eNOS pathways. Full article
Open AccessArticle New Briarane Diterpenoids from the Gorgonian Coral Junceella juncea
Mar. Drugs 2012, 10(6), 1321-1330; doi:10.3390/md10061321
Received: 29 March 2012 / Revised: 18 May 2012 / Accepted: 29 May 2012 / Published: 7 June 2012
Cited by 10 | PDF Full-text (688 KB) | HTML Full-text | XML Full-text
Abstract
Chemical investigation of Junceella juncea has resulted in the isolation of three new briaranes designated juncenolides M–O (13). The structures of these compounds were determined by spectroscopic analysis including 2D-NMR (COSY, HMBC and NOESY) and HRMS. Compound 1 [...] Read more.
Chemical investigation of Junceella juncea has resulted in the isolation of three new briaranes designated juncenolides M–O (13). The structures of these compounds were determined by spectroscopic analysis including 2D-NMR (COSY, HMBC and NOESY) and HRMS. Compound 1 is a new chlorinated briarane while compound 3 contains a rare methyl ester at C-16. The anti-inflammatory activities tested on superoxide anion generation and elastase release by human neutrophils in response to FMLP/CB were evaluated. Full article
Open AccessArticle Sinularones A–I, New Cyclopentenone and Butenolide Derivatives from a Marine Soft Coral Sinularia sp. and Their Antifouling Activity
Mar. Drugs 2012, 10(6), 1331-1344; doi:10.3390/md10061331
Received: 12 March 2012 / Revised: 16 April 2012 / Accepted: 4 June 2012 / Published: 11 June 2012
Cited by 23 | PDF Full-text (1180 KB) | HTML Full-text | XML Full-text
Abstract
Nine new compounds, namely sinularones A–I (19), characterized as cyclopentenone and butenolide-type analogues, were isolated from a soft coral Sinularia sp., together with a known butenolide (10). Their structures were elucidated by means of spectroscopic (IR, [...] Read more.
Nine new compounds, namely sinularones A–I (19), characterized as cyclopentenone and butenolide-type analogues, were isolated from a soft coral Sinularia sp., together with a known butenolide (10). Their structures were elucidated by means of spectroscopic (IR, MS, 1D and 2D NMR, CD) analysis. The absolute configurations were determined on the basis of CD and specific rotation data in association with the computed electronic circular dichroism (ECD) by time dependent density functional theory (TD DFT) at 6-31+G(d,p)//DFT B3LYP/6-31+G(d,p) level. Compounds 12 and 710 showed potent antifouling activities against the barnacle Balanus amphitrite. Full article
Open AccessArticle SD118-Xanthocillin X (1), a Novel Marine Agent Extracted from Penicillium commune, Induces Autophagy through the Inhibition of the MEK/ERK Pathway
Mar. Drugs 2012, 10(6), 1345-1359; doi:10.3390/md10061345
Received: 24 April 2012 / Revised: 29 May 2012 / Accepted: 30 May 2012 / Published: 11 June 2012
Cited by 15 | PDF Full-text (1777 KB) | HTML Full-text | XML Full-text
Abstract
A compound named SD118-xanthocillin X (1) (C18H12N2O2), isolated from Penicillium commune in a deep-sea sediment sample, has been shown to inhibit the growth of several cancer cell lines in vitro. In [...] Read more.
A compound named SD118-xanthocillin X (1) (C18H12N2O2), isolated from Penicillium commune in a deep-sea sediment sample, has been shown to inhibit the growth of several cancer cell lines in vitro. In the present study, we employed a growth inhibition assay and apoptotic analysis to identify the biological effect and detailed mechanism of SD118-xanthocillin X (1) in human hepatocellular carcinoma (HepG2) cells. SD118-xanthocillin X (1) demonstrated a concentration-dependent inhibitory effect on the growth of HepG2 cells and caused slight cellular apoptosis and significantly induced autophagy. Autophagy was detected as early as 12 h by the conversion of microtubule-associated protein 1 light chain 3 (LC3-I) to LC3-II, following cleavage and lipid addition to LC3-I. The pharmacological autophagy inhibitor 3-methyladenine largely attenuates the growth inhibition and autophagic effect of SD118-xanthocillin X (1) in HepG2 cells. Our data also indicated that the autophagic effect of SD118-xanthocillin X (1) occurs via the down-regulation of the MEK/ERK signaling pathway and the up-regulated class III PI3K/Beclin 1 signaling pathway. Full article
Open AccessArticle Production and Isolation of Azaspiracid-1 and -2 from Azadinium spinosum Culture in Pilot Scale Photobioreactors
Mar. Drugs 2012, 10(6), 1360-1382; doi:10.3390/md10061360
Received: 15 May 2012 / Revised: 1 June 2012 / Accepted: 4 June 2012 / Published: 13 June 2012
Cited by 12 | PDF Full-text (380 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Azaspiracid (AZA) poisoning has been reported following consumption of contaminated shellfish, and is of human health concern. Hence, it is important to have sustainable amounts of the causative toxins available for toxicological studies and for instrument calibration in monitoring programs, without having [...] Read more.
Azaspiracid (AZA) poisoning has been reported following consumption of contaminated shellfish, and is of human health concern. Hence, it is important to have sustainable amounts of the causative toxins available for toxicological studies and for instrument calibration in monitoring programs, without having to rely on natural toxin events. Continuous pilot scale culturing was carried out to evaluate the feasibility of AZA production using Azadinium spinosum cultures. Algae were harvested using tangential flow filtration or continuous centrifugation. AZAs were extracted using solid phase extraction (SPE) procedures, and subsequently purified. When coupling two stirred photobioreactors in series, cell concentrations reached 190,000 and 210,000 cell·mL−1 at steady state in bioreactors 1 and 2, respectively. The AZA cell quota decreased as the dilution rate increased from 0.15 to 0.3 day−1, with optimum toxin production at 0.25 day−1. After optimization, SPE procedures allowed for the recovery of 79 ± 9% of AZAs. The preparative isolation procedure previously developed for shellfish was optimized for algal extracts, such that only four steps were necessary to obtain purified AZA1 and -2. A purification efficiency of more than 70% was achieved, and isolation from 1200 L of culture yielded 9.3 mg of AZA1 and 2.2 mg of AZA2 of >95% purity. This work demonstrated the feasibility of sustainably producing AZA1 and -2 from A. spinosum cultures. Full article
Open AccessArticle Chalinulasterol, a Chlorinated Steroid Disulfate from the Caribbean Sponge Chalinula molitba. Evaluation of Its Role as PXR Receptor Modulator
Mar. Drugs 2012, 10(6), 1383-1390; doi:10.3390/md10061383
Received: 20 April 2012 / Revised: 17 May 2012 / Accepted: 1 June 2012 / Published: 14 June 2012
Cited by 3 | PDF Full-text (328 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Chalinulasterol (1) a new chlorinated sterol disulfate was isolated from the Caribbean sponge Chalinula molitba. Its structure was elucidated using mass spectrometry and NMR experiments. The possible role of chalinulasterol as modulator of the PXR nuclear receptor was investigated [...] Read more.
Chalinulasterol (1) a new chlorinated sterol disulfate was isolated from the Caribbean sponge Chalinula molitba. Its structure was elucidated using mass spectrometry and NMR experiments. The possible role of chalinulasterol as modulator of the PXR nuclear receptor was investigated but, in spite of the close structural relationship with the PXR agonist solomonsterol A (2), it showed no activity. The structural requirements for the PXR nuclear receptor activity were discussed. Full article
Open AccessArticle Anti-Oxidative, Anti-Tumor-Promoting, and Anti-Carcinogensis Activities of Nitroastaxanthin and Nitrolutein, the Reaction Products of Astaxanthin and Lutein with Peroxynitrite
Mar. Drugs 2012, 10(6), 1391-1399; doi:10.3390/md10061391
Received: 29 March 2012 / Revised: 7 June 2012 / Accepted: 13 June 2012 / Published: 18 June 2012
Cited by 11 | PDF Full-text (295 KB) | HTML Full-text | XML Full-text
Abstract
Astaxanthin captured peroxynitrite to form nitroastaxanthins. 15-Nitroastaxanthin was a major reaction product of astaxanthin with peroxynitrite. Here, the anti-oxidative, anti-tumor-promoting, and anti-carcinogensis activities of 15-nitroastaxanthin were investigated. In addition to astaxanthin, 15-nitroastaxanthin showed excellent singlet oxygen quenching activity. Furthermore, 15-nitroastaxanthin showed inhibitory [...] Read more.
Astaxanthin captured peroxynitrite to form nitroastaxanthins. 15-Nitroastaxanthin was a major reaction product of astaxanthin with peroxynitrite. Here, the anti-oxidative, anti-tumor-promoting, and anti-carcinogensis activities of 15-nitroastaxanthin were investigated. In addition to astaxanthin, 15-nitroastaxanthin showed excellent singlet oxygen quenching activity. Furthermore, 15-nitroastaxanthin showed inhibitory effects of in vitro Epstein-Barr virus early antigen activation and two-stage carcinogensis on mouse skin papillomas. These activities were slightly higher than those of astaxanthin. Similar results were obtained for the 15-nitrolutein, a major reaction product of lutein with peroxynitrite. Full article
(This article belongs to the Special Issue Marine Carotenoids and Oxidative Stress)
Open AccessArticle Pigmentation and Spectral Absorbance Signatures in Deep-Water Corals from the Trondheimsfjord, Norway
Mar. Drugs 2012, 10(6), 1400-1411; doi:10.3390/md10061400
Received: 3 April 2012 / Revised: 23 May 2012 / Accepted: 13 June 2012 / Published: 20 June 2012
Cited by 6 | PDF Full-text (3118 KB) | HTML Full-text | XML Full-text
Abstract
The pigmentation and corresponding in vivo and in vitro absorption characteristics in three different deep-water coral species: white and orange Lophelia pertusa, Paragorgia arborea and Primnoa resedaeformis, collected from the Trondheimsfjord are described. Pigments were isolated and characterized by High-Performance [...] Read more.
The pigmentation and corresponding in vivo and in vitro absorption characteristics in three different deep-water coral species: white and orange Lophelia pertusa, Paragorgia arborea and Primnoa resedaeformis, collected from the Trondheimsfjord are described. Pigments were isolated and characterized by High-Performance Liquid Chromatography (HPLC) analysis and High-Performance Liquid Chromatography Time-Of-Flight Mass Spectrometer (LC-TOF MS). The main carotenoids identified for all three coral species were astaxanthin and a canthaxanthin-like carotenoid. Soft tissue and skeleton of orange L. pertusa contained 2 times more astaxanthin g−1 wet weight compared to white L. pertusa. White and orange L. pertusa were characterized with in vivo absorbance peaks at 409 and 473 nm, respectively. In vivo absorbance maxima for P. arborea and P. resedaeformis was typically at 475 nm. The shapes of the absorbance spectra (400–700 nm) were species-specific, indicated by in vivo, in vitro and the corresponding difference spectra. The results may provide important chemotaxonomic information for pigment when bonded to their proteins in vivo, bio-prospecting, and for in situ identification, mapping and monitoring of corals. Full article
(This article belongs to the Special Issue Marine Carotenoids and Oxidative Stress)
Open AccessCommunication Total Synthesis of a Marine Alkaloid—Rigidin E
Mar. Drugs 2012, 10(6), 1412-1421; doi:10.3390/md10061412
Received: 28 May 2012 / Revised: 7 June 2012 / Accepted: 8 June 2012 / Published: 20 June 2012
Cited by 8 | PDF Full-text (506 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In the present paper, we report an efficient total synthesis of a marine alkaloid, rigidin E. The key tetrasubstituted 2-amino-3-carboxamidepyrrole intermediate was synthesized by cascade Michael addition/intramolecular cyclization between N-(2-(4-(benzyloxy)phenyl)-2-oxoethyl)methanesulfonamide and 3-(4-(benzyloxy)phenyl)-2-cyano-N-methylacrylamide. Subsequent carbonylation with triphosgene catalyzed by I [...] Read more.
In the present paper, we report an efficient total synthesis of a marine alkaloid, rigidin E. The key tetrasubstituted 2-amino-3-carboxamidepyrrole intermediate was synthesized by cascade Michael addition/intramolecular cyclization between N-(2-(4-(benzyloxy)phenyl)-2-oxoethyl)methanesulfonamide and 3-(4-(benzyloxy)phenyl)-2-cyano-N-methylacrylamide. Subsequent carbonylation with triphosgene catalyzed by I2 and deprotection of benzyl groups afforded rigidin E in 21% overall yield. This strategy has the merits of metal-free reactions, low cost, mild reaction protocols, and easy access to diversity-oriented derivatives for potential structure-activity relationship investigation. Full article

Review

Jump to: Research

Open AccessReview Conotoxins that Confer Therapeutic Possibilities
Mar. Drugs 2012, 10(6), 1244-1265; doi:10.3390/md10061244
Received: 6 February 2012 / Revised: 24 April 2012 / Accepted: 24 May 2012 / Published: 4 June 2012
Cited by 29 | PDF Full-text (425 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Cone snails produce a distinctive repertoire of venom peptides that are used both as a defense mechanism and also to facilitate the immobilization and digestion of prey. These peptides target a wide variety of voltage- and ligand-gated ion channels, which make them [...] Read more.
Cone snails produce a distinctive repertoire of venom peptides that are used both as a defense mechanism and also to facilitate the immobilization and digestion of prey. These peptides target a wide variety of voltage- and ligand-gated ion channels, which make them an invaluable resource for studying the properties of these ion channels in normal and diseased states, as well as being a collection of compounds of potential pharmacological use in their own right. Examples include the United States Food and Drug Administration (FDA) approved pharmaceutical drug, Ziconotide (Prialt®; Elan Pharmaceuticals, Inc.) that is the synthetic equivalent of the naturally occurring ω-conotoxin MVIIA, whilst several other conotoxins are currently being used as standard research tools and screened as potential therapeutic drugs in pre-clinical or clinical trials. These developments highlight the importance of driving conotoxin-related research. A PubMed query from 1 January 2007 to 31 August 2011 combined with hand-curation of the retrieved articles allowed for the collation of 98 recently identified conotoxins with therapeutic potential which are selectively discussed in this review. Protein sequence similarity analysis tentatively assigned uncharacterized conotoxins to predicted functional classes. Furthermore, conotoxin therapeutic potential for neurodegenerative disorders (NDD) was also inferred. Full article
Figures

Journal Contact

MDPI AG
Marine Drugs Editorial Office
St. Alban-Anlage 66, 4052 Basel, Switzerland
marinedrugs@mdpi.com
Tel. +41 61 683 77 34
Fax: +41 61 302 89 18
Editorial Board
Contact Details Submit to Marine Drugs
Back to Top