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Topical Collection "Bioactive Compounds from Marine Invertebrates"

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A topical collection in Marine Drugs (ISSN 1660-3397).

Editor

Collection Editor
Dr. Kirsten Benkendorff

Marine Ecology Research Centre, Southern Cross University, PO Box 157, Military Road, Lismore NSW 2480, Australia
Website | E-Mail
Phone: 61 2 6620 3755
Fax: +61 2 66212669
Interests: bioactive compounds from marine molluscs; marine pigments and dyes; molluscan immune systems

Topical Collection Information

Dear Colleagues,

All major lineages of invertebrates evolved in the oceans, and as such, the marine environment harbors the largest diversity of invertebrate phyla and species. As part of the struggle for survival, all extant marine invertebrate species occupy a unique niche within the marine environment, with specific adaptations to withstand a wide range of abiotic and biotic pressures. Many of these marine invertebrates are sessile or slow moving, and lack physical defense structures to protect against potential predators and competitors. They all also lack adaptive immunity against pathogens and parasites, despite being constantly bathed in microorganisms, and thus rely entirely on effective innate immune systems to keep themselves free of infection. To compensate for these apparent deficiencies, marine invertebrates have developed an arsenal of bioactive secondary metabolites. In addition to these chemically mediated defense interactions, some marine invertebrates use water soluble secondary metabolites for chemical communication (pheromones, settlement cues) and neurotoxins (in venoms) to paralyze or kill their prey.

Many of these intrinsically biologically active compounds produced by marine invertebrates provide useful leads for pharmaceutical, nutraceutical, and other industrial (e.g., anti-fouling) development. However, sustainable production is often limited by molecular complexity, which can limit economical chemical synthesis. Further insight into the ecology of the source species is required, including knowledge of the biosynthetic origin of the bioactive compounds, so as to distinguish innately synthesized, dietary derived or symbiotic microbial sources for sustainable culture. Investigation into the diversity and function of marine invertebrate secondary metabolites is also a vital step towards developing a comprehensive understanding of how chemicals might help structure marine populations, communities, and ecosystems.

In this collection, we hope to explore all aspects of bioactive secondary metabolism in marine invertebrates, including the chemical diversity within certain invertebrate taxa, chemical ecology research aimed at elucidating the natural function of bioactive secondary metabolites, and the neuroecology of marine natural products, as well as bioactivity profiles, biosynthesis, and/or biodistributional studies on specific marine invertebrate natural products. We would also be interested in highlighting recent innovative research on the sustainable production, biomedical or industrial, of marine invertebrate natural products, or research into the traditional use of marine invertebrates that produce bioactive compounds. We welcome the submission of comprehensive/mini reviews, original research articles, and communications.

As guest editor, I invite you to contribute to the Marine Drugs collection on “Bioactive Compounds from Marine Invertebrates”.

Dr. Kirsten Benkendorff
Collection 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. Papers will be published continuously (as soon as accepted) and will be listed together on the collection 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

  • ascidian secondary metabolites
  • sponge secondary metabolites
  • cnidarian secondary metabolites
  • mollusc secondary metabolites
  • echinoderm secondary metabolites
  • chemical defense
  • marine chemical ecology
  • antimicrobial activity
  • antiviral activity
  • anti-inflammatory activity
  • anticancer activity
  • neurotoxin
  • pheromone
  • sustainable supply

Published Papers (50 papers)

2016

Jump to: 2014, 2013

Open AccessArticle Anti-Melanogenic Activity of Gagunin D, a Highly Oxygenated Diterpenoid from the Marine Sponge Phorbas sp., via Modulating Tyrosinase Expression and Degradation
Mar. Drugs 2016, 14(11), 212; doi:10.3390/md14110212
Received: 10 October 2016 / Revised: 10 November 2016 / Accepted: 14 November 2016 / Published: 17 November 2016
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Abstract
Tyrosinase is the rate-limiting enzyme critical for melanin synthesis and controls pigmentation in the skin. The inhibition of tyrosinase is currently the most common approach for the development of skin-whitening cosmetics. Gagunin D (GD), a highly oxygenated diterpenoid isolated from the marine sponge
[...] Read more.
Tyrosinase is the rate-limiting enzyme critical for melanin synthesis and controls pigmentation in the skin. The inhibition of tyrosinase is currently the most common approach for the development of skin-whitening cosmetics. Gagunin D (GD), a highly oxygenated diterpenoid isolated from the marine sponge Phorbas sp., has exhibited cytotoxicity toward human leukemia cells. However, the effect of GD on normal cells and the molecular mechanisms remain to be elucidated. In the present study, we identified for the first time the anti-melanogenic activity of GD and its precise underlying mechanisms in mouse melan-a cells. GD significantly inhibited melanin synthesis in the melan-a cells and a reconstructed human skin model. Further analysis revealed that GD suppressed the expression of tyrosinase and increased the rate of tyrosinase degradation. GD also inhibited tyrosinase enzymatic activity. In addition, GD effectively suppressed the expression of proteins associated with melanosome transfer. These findings suggest that GD is a potential candidate for cosmetic formulations due to its multi-functional properties. Full article
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Open AccessReview Ceramide as a Target of Marine Triterpene Glycosides for Treatment of Human Myeloid Leukemia
Mar. Drugs 2016, 14(11), 205; doi:10.3390/md14110205
Received: 13 September 2016 / Revised: 19 October 2016 / Accepted: 28 October 2016 / Published: 3 November 2016
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Abstract
Acute myeloid leukemia (AML) is a heterogeneous myeloid clonal disorder exhibiting the accumulation of immature myeloid progenitors in the bone marrow and peripheral blood. Standard AML therapy requires intensive combination chemotherapy, which leads to significant treatment-related toxicity. The search for new, low toxic
[...] Read more.
Acute myeloid leukemia (AML) is a heterogeneous myeloid clonal disorder exhibiting the accumulation of immature myeloid progenitors in the bone marrow and peripheral blood. Standard AML therapy requires intensive combination chemotherapy, which leads to significant treatment-related toxicity. The search for new, low toxic marine agents, inducing the generation of ceramide in leukemic cells is a new approach to improve the therapy of leukemia. This review focuses on the metabolism of sphingolipids, the role of ceramide in treating leukemia, and the antitumor activity, related to ceramide metabolism, of some marine metabolites, particularly stichoposides, triterpene glycosides extracted from sea cucumbers of the family Stichopodiidae. Full article
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Open AccessArticle Evaluation of the Antioxidant Activity of the Marine Pyrroloiminoquinone Makaluvamines
Mar. Drugs 2016, 14(11), 197; doi:10.3390/md14110197
Received: 26 September 2016 / Revised: 19 October 2016 / Accepted: 20 October 2016 / Published: 27 October 2016
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Abstract
Makaluvamines are pyrroloiminoquinones isolated from Zyzzya sponges. Until now, they have been described as topoisomerase II inhibitors with cytotoxic effects in diverse tumor cell lines. In the present work, seven makaluvamines were tested in several antioxidant assays in primary cortical neurons and neuroblastoma
[...] Read more.
Makaluvamines are pyrroloiminoquinones isolated from Zyzzya sponges. Until now, they have been described as topoisomerase II inhibitors with cytotoxic effects in diverse tumor cell lines. In the present work, seven makaluvamines were tested in several antioxidant assays in primary cortical neurons and neuroblastoma cells. Among the alkaloids studied, makaluvamine J was the most active in all the assays. This compound was able to reduce the mitochondrial damage elicited by the well-known stressor H2O2. The antioxidant properties of makaluvamine J are related to an improvement of the endogenous antioxidant defenses of glutathione and catalase. SHSY5Y assays proved that this compound acts as a Nrf2 activator leading to an improvement of antioxidant defenses. A low concentration of 10 nM is able to reduce the reactive oxygen species release and maintain a correct mitochondrial function. Based on these results, non-substituted nitrogen in the pyrrole plus the presence of a p-hydroxystyryl without a double bond seems to be the most active structure with a complete antioxidant effect in neuronal cells. Full article
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Open AccessArticle Novel Conopeptides of Largely Unexplored Indo Pacific Conus sp.
Mar. Drugs 2016, 14(11), 199; doi:10.3390/md14110199
Received: 18 August 2016 / Revised: 13 September 2016 / Accepted: 15 October 2016 / Published: 27 October 2016
Cited by 1 | PDF Full-text (4441 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Cone snails are predatory creatures using venom as a weapon for prey capture and defense. Since this venom is neurotoxic, the venom gland is considered as an enormous collection of pharmacologically interesting compounds having a broad spectrum of targets. As such, cone snail
[...] Read more.
Cone snails are predatory creatures using venom as a weapon for prey capture and defense. Since this venom is neurotoxic, the venom gland is considered as an enormous collection of pharmacologically interesting compounds having a broad spectrum of targets. As such, cone snail peptides represent an interesting treasure for drug development. Here, we report five novel peptides isolated from the venom of Conus longurionis, Conus asiaticus and Conus australis. Lo6/7a and Lo6/7b were retrieved from C. longurionis and have a cysteine framework VI/VII. Lo6/7b has an exceptional amino acid sequence because no similar conopeptide has been described to date (similarity percentage <50%). A third peptide, Asi3a from C. asiaticus, has a typical framework III Cys arrangement, classifying the peptide in the M-superfamily. Asi14a, another peptide of C. asiaticus, belongs to framework XIV peptides and has a unique amino acid sequence. Finally, AusB is a novel conopeptide from C. australis. The peptide has only one disulfide bond, but is structurally very different as compared to other disulfide-poor peptides. The peptides were screened on nAChRs, NaV and KV channels depending on their cysteine framework and proposed classification. No targets could be attributed to the peptides, pointing to novel functionalities. Moreover, in the quest of identifying novel pharmacological targets, the peptides were tested for antagonistic activity against a broad panel of Gram-negative and Gram-positive bacteria, as well as two yeast strains. Full article
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Open AccessCommunication Degree of Suppression of Mouse Myoblast Cell Line C2C12 Differentiation Varies According to Chondroitin Sulfate Subtype
Mar. Drugs 2016, 14(10), 193; doi:10.3390/md14100193
Received: 15 September 2016 / Revised: 12 October 2016 / Accepted: 17 October 2016 / Published: 21 October 2016
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Abstract
Chondroitin sulfate (CS), a type of glycosaminoglycan (GAG), is a factor involved in the suppression of myogenic differentiation. CS comprises two repeating sugars and has different subtypes depending on the position and number of bonded sulfate groups. However, the effect of each subtype
[...] Read more.
Chondroitin sulfate (CS), a type of glycosaminoglycan (GAG), is a factor involved in the suppression of myogenic differentiation. CS comprises two repeating sugars and has different subtypes depending on the position and number of bonded sulfate groups. However, the effect of each subtype on myogenic differentiation remains unclear. In this study, we spiked cultures of C2C12 myoblasts, cells which are capable of undergoing skeletal muscle differentiation, with one of five types of CS (CS-A, -B, -C, -D, or -E) and induced differentiation over a fixed time. After immunostaining of the formed myotubes with an anti-MHC antibody, we counted the number of nuclei in the myotubes and then calculated the fusion index (FI) as a measure of myotube differentiation. The FI values of all the CS-treated groups were lower than the FI value of the control group, especially the group treated with CS-E, which displayed notable suppression of myotube formation. To confirm that the sugar chain in CS-E is important in the suppression of differentiation, chondroitinase ABC (ChABC), which catabolizes CS, was added to the media. The addition of ChABC led to the degradation of CS-E, and neutralized the suppression of myotube formation by CS-E. Collectively, it can be concluded that the degree of suppression of differentiation depends on the subtype of CS and that CS-E strongly suppresses myogenic differentiation. We conclude that the CS sugar chain has inhibitory action against myoblast cell fusion. Full article
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Open AccessArticle Three New Cytotoxic Polyhydroxysteroidal Glycosides from Starfish Craspidaster hesperus
Mar. Drugs 2016, 14(10), 189; doi:10.3390/md14100189
Received: 14 August 2016 / Revised: 9 October 2016 / Accepted: 11 October 2016 / Published: 19 October 2016
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Abstract
Three new polyhydroxysteroidal glycosides, hesperuside A (1), B (2), and C (3), as well as a known novaeguinoside A (4), were isolated from the ethanol extract of starfish Craspidaster hesperus collected from the South China
[...] Read more.
Three new polyhydroxysteroidal glycosides, hesperuside A (1), B (2), and C (3), as well as a known novaeguinoside A (4), were isolated from the ethanol extract of starfish Craspidaster hesperus collected from the South China Sea. Their structures were elucidated by extensive spectroscopic methods and chemical evidence. The compounds 13 present unprecedented carbohydrate chain 3-O-methyl-β-d-galactopyranose, which differ from each other in the side chains. These compounds exhibited cytotoxicity against human tumor cells BEL-7402, MOLT-4, and A-549 in vitro. Full article
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Open AccessArticle Angiotensin-I Converting Enzyme (ACE) Inhibitory and Anti-Hypertensive Effect of Protein Hydrolysate from Actinopyga lecanora (Sea Cucumber) in Rats
Mar. Drugs 2016, 14(10), 176; doi:10.3390/md14100176
Received: 2 March 2016 / Revised: 8 July 2016 / Accepted: 19 July 2016 / Published: 30 September 2016
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Abstract
Food protein hydrolysates are known to exhibit angiotensin converting enzyme (ACE) inhibitory properties and can be used as a novel functional food for prevention of hypertension. This study evaluated the ACE inhibitory potentials of Actinopyga lecanora proteolysate (ALP) in vivo. The pre-fed rats
[...] Read more.
Food protein hydrolysates are known to exhibit angiotensin converting enzyme (ACE) inhibitory properties and can be used as a novel functional food for prevention of hypertension. This study evaluated the ACE inhibitory potentials of Actinopyga lecanora proteolysate (ALP) in vivo. The pre-fed rats with ALP at various doses (200, 400, 800 mg/kg body weight) exhibited a significant (p ≤ 0.05) suppression effect after inducing hypertension. To determine the optimum effective dose that will produce maximal reduction in blood pressure, ALP at three doses was fed to the rats after inducing hypertension. The results showed that the 800 mg/kg body weight dose significantly reduced blood pressure without noticeable negative physiological effect. In addition, there were no observable changes in the rats’ heart rate after oral administration of the ALP. It was concluded that Actinopyga lecanora proteolysate could potentially be used for the development of functional foods and nutraceuticals for prevention and treatment of hypertension. Full article
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Open AccessArticle Mirabolides A and B; New Cytotoxic Glycerides from the Red Sea Sponge Theonella mirabilis
Mar. Drugs 2016, 14(8), 155; doi:10.3390/md14080155
Received: 15 May 2016 / Revised: 5 August 2016 / Accepted: 8 August 2016 / Published: 18 August 2016
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Abstract
As a part of our continuing work to find out bioactive lead molecules from marine invertebrates, the CHCl3 fraction of the organic extract of the Red Sea sponge Theonella mirabilis showed cytotoxic activity in our primary screen. Bioassay-guided purification of the active
[...] Read more.
As a part of our continuing work to find out bioactive lead molecules from marine invertebrates, the CHCl3 fraction of the organic extract of the Red Sea sponge Theonella mirabilis showed cytotoxic activity in our primary screen. Bioassay-guided purification of the active fractions of the sponge’s extract resulted in the isolation of two new glycerides, mirabolides A and B (1 and 2), together with the reported 4-methylene sterols, conicasterol (3) and swinhosterol B (4). The structures of the compounds were assigned by interpretation of their 1D (1H, 13C), 2D (COSY, HSQC, HMBC, ROESY) NMR spectral data and high-resolution mass determinations. Compounds 14 displayed marked cytotoxic activity against human breast adenocarcinoma cell line (MCF-7) with IC50 values of 16.4, 5.18, 6.23 and 3.0 μg/mL, respectively, compared to 5.4 μg/mL observed by doxorubicin as reference drug. Full article
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Open AccessArticle Anti-Dengue Virus Constituents from Formosan Zoanthid Palythoa mutuki
Mar. Drugs 2016, 14(8), 151; doi:10.3390/md14080151
Received: 3 June 2016 / Revised: 21 July 2016 / Accepted: 29 July 2016 / Published: 9 August 2016
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Abstract
A new marine ecdysteroid with an α-hydroxy group attaching at C-4 instead of attaching at C-2 and C-3, named palythone A (1), together with eight known compounds (29) were obtained from the ethanolic extract of the Formosan
[...] Read more.
A new marine ecdysteroid with an α-hydroxy group attaching at C-4 instead of attaching at C-2 and C-3, named palythone A (1), together with eight known compounds (29) were obtained from the ethanolic extract of the Formosan zoanthid Palythoa mutuki. The structures of those compounds were mainly determined by NMR spectroscopic data analyses. The absolute configuration of 1 was further confirmed by comparing experimental and calculated circular dichroism (CD) spectra. Anti-dengue virus 2 activity and cytotoxicity of five isolated compounds were evaluated using virus infectious system and [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assays, respectively. As a result, peridinin (9) exhibited strong antiviral activity (IC50 = 4.50 ± 0.46 μg/mL), which is better than that of the positive control, 2′CMC. It is the first carotene-like substance possessing anti-dengue virus activity. In addition, the structural diversity and bioactivity of the isolates were compared by using a ChemGPS–NP computational analysis. The ChemGPS–NP data suggested natural products with anti-dengue virus activity locate closely in the chemical space. Full article
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Open AccessReview Acetylated Triterpene Glycosides and Their Biological Activity from Holothuroidea Reported in the Past Six Decades
Mar. Drugs 2016, 14(8), 147; doi:10.3390/md14080147
Received: 20 June 2016 / Revised: 17 July 2016 / Accepted: 19 July 2016 / Published: 4 August 2016
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Abstract
Sea cucumbers have been valued for many centuries as a tonic and functional food, dietary delicacies and important ingredients of traditional medicine in many Asian countries. An assortment of bioactive compounds has been described in sea cucumbers. The most important and abundant secondary
[...] Read more.
Sea cucumbers have been valued for many centuries as a tonic and functional food, dietary delicacies and important ingredients of traditional medicine in many Asian countries. An assortment of bioactive compounds has been described in sea cucumbers. The most important and abundant secondary metabolites from sea cucumbers are triterpene glycosides (saponins). Due to the wide range of their potential biological activities, these natural compounds have gained attention and this has led to their emergence as high value compounds with extended application in nutraceutical, cosmeceutical, medicinal and pharmaceutical products. They are characterized by bearing a wide spectrum of structures, such as sulfated, non-sulfated and acetylated glycosides. Over 700 triterpene glycosides have been reported from the Holothuroidea in which more than 145 are decorated with an acetoxy group having 38 different aglycones. The majority of sea cucumber triterpene glycosides are of the holostane type containing a C18 (20) lactone group and either Δ7(8) or Δ9(11) double bond in their genins. The acetoxy group is mainly connected to the C-16, C-22, C-23 and/or C-25 of their aglycone. Apparently, the presence of an acetoxy group, particularly at C-16 of the aglycone, plays a significant role in the bioactivity; including induction of caspase, apoptosis, cytotoxicity, anticancer, antifungal and antibacterial activities of these compounds. This manuscript highlights the structure of acetylated saponins, their biological activity, and their structure-activity relationships. Full article
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Open AccessArticle Topsensterols A–C, Cytotoxic Polyhydroxylated Sterol Derivatives from a Marine Sponge Topsentia sp.
Mar. Drugs 2016, 14(8), 146; doi:10.3390/md14080146
Received: 14 June 2016 / Revised: 16 July 2016 / Accepted: 26 July 2016 / Published: 1 August 2016
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Abstract
Three new polyhydroxylated sterol derivatives topsensterols A–C (13) have been isolated from a marine sponge Topsentia sp. collected from the South China Sea. Their structures were elucidated by detailed analysis of the spectroscopic data, especially the NOESY spectra. Topsensterols
[...] Read more.
Three new polyhydroxylated sterol derivatives topsensterols A–C (13) have been isolated from a marine sponge Topsentia sp. collected from the South China Sea. Their structures were elucidated by detailed analysis of the spectroscopic data, especially the NOESY spectra. Topsensterols A–C (l3) possess novel 2β,3α,4β,6α-tetrahydroxy-14α-methyl Δ9(11) steroidal nuclei with unusual side chains. Compound 2 exhibited cytotoxicity against human gastric carcinoma cell line SGC-7901 with an IC50 value of 8.0 μM. Compound 3 displayed cytotoxicity against human erythroleukemia cell line K562 with an IC50 value of 6.0 μM. Full article
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Open AccessReview The Role of Spongia sp. in the Discovery of Marine Lead Compounds
Mar. Drugs 2016, 14(8), 139; doi:10.3390/md14080139
Received: 16 June 2016 / Revised: 6 July 2016 / Accepted: 8 July 2016 / Published: 23 July 2016
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Abstract
A comprehensive review on the chemistry of Spongia sp. is here presented, together with the biological activity of the isolated compounds. The compounds are grouped in sesquiterpene quinones, diterpenes, C21 and other linear furanoterpenes, sesterterpenes, sterols (including secosterols), macrolides and miscellaneous compounds. Among
[...] Read more.
A comprehensive review on the chemistry of Spongia sp. is here presented, together with the biological activity of the isolated compounds. The compounds are grouped in sesquiterpene quinones, diterpenes, C21 and other linear furanoterpenes, sesterterpenes, sterols (including secosterols), macrolides and miscellaneous compounds. Among other reports we include studies on the intraspecific diversity of a Mediterranean species, compounds isolated from associated sponge and nudibranch and compounds isolated from S. zimocca and the red seaweed Laurentia microcladia. Under biological activity a table of the reported biological activities of the various compounds and the biological screening of extracts are described. The present review covers the literature from 1971 to 2015. Full article
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Open AccessArticle Transcriptome of the Australian Mollusc Dicathais orbita Provides Insights into the Biosynthesis of Indoles and Choline Esters
Mar. Drugs 2016, 14(7), 135; doi:10.3390/md14070135
Received: 16 May 2016 / Revised: 8 July 2016 / Accepted: 12 July 2016 / Published: 20 July 2016
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Abstract
Dicathais orbita is a mollusc of the Muricidae family and is well known for the production of the expensive dye Tyrian purple and its brominated precursors that have anticancer properties, in addition to choline esters with muscle-relaxing properties. However, the biosynthetic pathways that
[...] Read more.
Dicathais orbita is a mollusc of the Muricidae family and is well known for the production of the expensive dye Tyrian purple and its brominated precursors that have anticancer properties, in addition to choline esters with muscle-relaxing properties. However, the biosynthetic pathways that produce these secondary metabolites in D. orbita are not known. Illumina HiSeq 2000 transcriptome sequencing of hypobranchial glands, prostate glands, albumen glands, capsule glands, and mantle and foot tissues of D. orbita generated over 201 million high quality reads that were de novo assembled into 219,437 contigs. Annotation with reference to the Nr, Swiss-Prot and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases identified candidate-coding regions in 76,152 of these contigs, with transcripts for many enzymes in various metabolic pathways associated with secondary metabolite biosynthesis represented. This study revealed that D. orbita expresses a number of genes associated with indole, sulfur and histidine metabolism pathways that are relevant to Tyrian purple precursor biosynthesis, and many of which were not found in the fully annotated genomes of three other molluscs in the KEGG database. However, there were no matches to known bromoperoxidase enzymes within the D. orbita transcripts. These transcriptome data provide a significant molecular resource for gastropod research in general and Tyrian purple producing Muricidae in particular. Full article
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Open AccessArticle Guanidine Alkaloids from the Marine Sponge Monanchora pulchra Show Cytotoxic Properties and Prevent EGF-Induced Neoplastic Transformation in Vitro
Mar. Drugs 2016, 14(7), 133; doi:10.3390/md14070133
Received: 18 May 2016 / Revised: 5 July 2016 / Accepted: 8 July 2016 / Published: 15 July 2016
PDF Full-text (4244 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Guanidine alkaloids from sponges Monanchora spp. represent diverse bioactive compounds, however, the mechanisms underlying bioactivity are very poorly understood. Here, we report results of studies on cytotoxic action, the ability to inhibit EGF-induced neoplastic transformation, and the effects on MAPK/AP-1 signaling of eight
[...] Read more.
Guanidine alkaloids from sponges Monanchora spp. represent diverse bioactive compounds, however, the mechanisms underlying bioactivity are very poorly understood. Here, we report results of studies on cytotoxic action, the ability to inhibit EGF-induced neoplastic transformation, and the effects on MAPK/AP-1 signaling of eight rare guanidine alkaloids, recently isolated from the marine sponge Monanchora pulchra, namely: monanchocidin A (1), monanchocidin B (2), monanchomycalin C (3), ptilomycalin A (4), monanchomycalin B (5), normonanchocidin D (6), urupocidin A (7), and pulchranin A (8). All of the compounds induced cell cycle arrest (apart from 8) and programmed death of cancer cells. Ptilomycalin A-like compounds 16 activated JNK1/2 and ERK1/2, following AP-1 activation and caused p53-independent programmed cell death. Compound 7 induced p53-independent cell death without activation of AP-1 or caspase-3/7, and the observed JNK1/2 activation did not contribute to the cytotoxic effect of the compound. Alkaloid 8 induced JNK1/2 (but not ERK1/2) activation leading to p53-independent cell death and strong suppression of AP-1 activity. Alkaloids 14, 7, and 8 were able to inhibit the EGF-induced neoplastic transformation of JB6 P+ Cl41 cells. Our results suggest that investigated guanidine marine alkaloids hold potential to eliminate human cancer cells and prevent cancer cell formation and spreading. Full article
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Open AccessReview To Pee, or Not to Pee: A Review on Envenomation and Treatment in European Jellyfish Species
Mar. Drugs 2016, 14(7), 127; doi:10.3390/md14070127
Received: 13 May 2016 / Revised: 27 June 2016 / Accepted: 30 June 2016 / Published: 8 July 2016
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Abstract
There is a growing cause for concern on envenoming European species because of jellyfish blooms, climate change and globalization displacing species. Treatment of envenomation involves the prevention of further nematocyst release and relieving local and systemic symptoms. Many anecdotal treatments are available but
[...] Read more.
There is a growing cause for concern on envenoming European species because of jellyfish blooms, climate change and globalization displacing species. Treatment of envenomation involves the prevention of further nematocyst release and relieving local and systemic symptoms. Many anecdotal treatments are available but species-specific first aid response is essential for effective treatment. However, species identification is difficult in most cases. There is evidence that oral analgesics, seawater, baking soda slurry and 42–45 °C hot water are effective against nematocyst inhibition and giving pain relief. The application of topical vinegar for 30 s is effective on stings of specific species. Treatments, which produce osmotic or pressure changes can exacerbate the initial sting and aggravate symptoms, common among many anecdotal treatments. Most available therapies are based on weak evidence and thus it is strongly recommended that randomized clinical trials are undertaken. We recommend a vital increase in directed research on the effect of environmental factors on envenoming mechanisms and to establish a species-specific treatment. Adequate signage on jellyfish stings and standardized first aid protocols with emphasis on protective equipment and avoidance of jellyfish to minimize cases should be implemented in areas at risk. Full article
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Open AccessArticle Antiproliferative Scalarane-Based Metabolites from the Red Sea Sponge Hyrtios erectus
Mar. Drugs 2016, 14(7), 130; doi:10.3390/md14070130
Received: 13 April 2016 / Revised: 16 May 2016 / Accepted: 27 June 2016 / Published: 8 July 2016
PDF Full-text (3010 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two new sesterterpenes analogs, namely, 12-acetoxy,16-epi-hyrtiolide (1) and 12β-acetoxy,16β-methoxy,20α-hydroxy-17-scalaren-19,20-olide (2), containing a scalarane-based framework along with seven previously reported scalarane-type sesterterpenes (39) have been isolated from the sponge Hyrtios erectus (order Dictyoceratida) collected
[...] Read more.
Two new sesterterpenes analogs, namely, 12-acetoxy,16-epi-hyrtiolide (1) and 12β-acetoxy,16β-methoxy,20α-hydroxy-17-scalaren-19,20-olide (2), containing a scalarane-based framework along with seven previously reported scalarane-type sesterterpenes (39) have been isolated from the sponge Hyrtios erectus (order Dictyoceratida) collected from the Red Sea, Egypt. The structures of the isolated compounds were elucidated on the basis of their spectroscopic data and comparison with reported NMR data. Compounds 19 exhibited considerable antiproliferative activity against breast adenocarcinoma (MCF-7), colorectal carcinoma (HCT-116) and hepatocellular carcinoma cells (HepG2). Compounds 3, 5 and 9 were selected for subsequent investigations regarding their mechanism of cell death induction (differential apoptosis/necrosis assessment) and their influence on cell cycle distribution. Full article
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Open AccessArticle Absorption and Transport of Sea Cucumber Saponins from Apostichopus japonicus
Mar. Drugs 2016, 14(6), 114; doi:10.3390/md14060114
Received: 14 March 2016 / Revised: 27 May 2016 / Accepted: 7 June 2016 / Published: 17 June 2016
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Abstract
The present study is focused on the intestinal absorption of sea cucumber saponins. We determined the pharmacokinetic characteristics and bioavailability of Echinoside A and Holotoxin A1; the findings indicated that the bioavailability of Holotoxin A1 was lower than Echinoside A.
[...] Read more.
The present study is focused on the intestinal absorption of sea cucumber saponins. We determined the pharmacokinetic characteristics and bioavailability of Echinoside A and Holotoxin A1; the findings indicated that the bioavailability of Holotoxin A1 was lower than Echinoside A. We inferred that the differences in chemical structure between compounds was a factor that explained their different characteristics of transport across the intestine. In order to confirm the absorption characteristics of Echinoside A and Holotoxin A1, we examined their transport across Caco-2 cell monolayer and effective permeability by single-pass intestinal perfusion. The results of Caco-2 cell model indicate that Echinoside A is transported by passive diffusion, and not influenced by the exocytosis of P-glycoprotein (P-gp, expressed in the apical side of Caco-2 monolayers as the classic inhibitor). The intestinal perfusion also demonstrated well the absorption of Echinoside A and poor absorption of Holotoxin A1, which matched up with the result of the Caco-2 cell model. The results demonstrated our conjecture and provides fundamental information on the relationship between the chemical structure of these sea cucumber saponins and their absorption characteristics, and we believe that our findings build a foundation for the further metabolism study of sea cucumber saponins and contribute to the further clinical research of saponins. Full article
Open AccessArticle Cembranoids from a Chinese Collection of the Soft Coral Lobophytum crassum
Mar. Drugs 2016, 14(6), 111; doi:10.3390/md14060111
Received: 25 April 2016 / Revised: 19 May 2016 / Accepted: 23 May 2016 / Published: 3 June 2016
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Abstract
Ten new cembrane-based diterpenes, locrassumins A–G (17), (–)-laevigatol B (8), (–)-isosarcophine (9), and (–)-7R,8S-dihydroxydeepoxysarcophytoxide (10), were isolated from a South China Sea collection of the soft coral Lobophytum crassum
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Ten new cembrane-based diterpenes, locrassumins A–G (17), (–)-laevigatol B (8), (–)-isosarcophine (9), and (–)-7R,8S-dihydroxydeepoxysarcophytoxide (10), were isolated from a South China Sea collection of the soft coral Lobophytum crassum, together with eight known analogues (1118). The structures of the new compounds were determined by extensive spectroscopic analysis and by comparison with previously reported data. Locrassumin C (3) possesses an unprecedented tetradecahydrobenzo[3,4]cyclobuta[1,2][8]annulene ring system. Compounds 1, 7, 12, 13, and 17 exhibited moderate inhibition against lipopolysaccharide (LPS)-induced nitric oxide (NO) production with IC50 values of 8–24 μM. Full article
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Open AccessReview Marine Invertebrate Metabolites with Anticancer Activities: Solutions to the “Supply Problem”
Mar. Drugs 2016, 14(5), 98; doi:10.3390/md14050098
Received: 29 March 2016 / Revised: 29 April 2016 / Accepted: 5 May 2016 / Published: 21 May 2016
Cited by 2 | PDF Full-text (2899 KB) | HTML Full-text | XML Full-text
Abstract
Marine invertebrates provide a rich source of metabolites with anticancer activities and several marine-derived agents have been approved for the treatment of cancer. However, the limited supply of promising anticancer metabolites from their natural sources is a major hurdle to their preclinical and
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Marine invertebrates provide a rich source of metabolites with anticancer activities and several marine-derived agents have been approved for the treatment of cancer. However, the limited supply of promising anticancer metabolites from their natural sources is a major hurdle to their preclinical and clinical development. Thus, the lack of a sustainable large-scale supply has been an important challenge facing chemists and biologists involved in marine-based drug discovery. In the current review we describe the main strategies aimed to overcome the supply problem. These include: marine invertebrate aquaculture, invertebrate and symbiont cell culture, culture-independent strategies, total chemical synthesis, semi-synthesis, and a number of hybrid strategies. We provide examples illustrating the application of these strategies for the supply of marine invertebrate-derived anticancer agents. Finally, we encourage the scientific community to develop scalable methods to obtain selected metabolites, which in the authors’ opinion should be pursued due to their most promising anticancer activities. Full article
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Open AccessArticle Structure and Bioactivity of a Modified Peptide Derived from the LPS-Binding Domain of an Anti-Lipopolysaccharide Factor (ALF) of Shrimp
Mar. Drugs 2016, 14(5), 96; doi:10.3390/md14050096
Received: 3 March 2016 / Revised: 9 May 2016 / Accepted: 10 May 2016 / Published: 19 May 2016
Cited by 2 | PDF Full-text (8763 KB) | HTML Full-text | XML Full-text
Abstract
The lipopolysaccharide binding domain (LBD) in anti-lipopolysaccharide factor (ALF) is the main functional element of ALF, which exhibits antimicrobial activities. Our previous studies show that the peptide LBDv, synthesized based on the modified sequence of LBD (named LBD2) from FcALF2, exhibited an apparently
[...] Read more.
The lipopolysaccharide binding domain (LBD) in anti-lipopolysaccharide factor (ALF) is the main functional element of ALF, which exhibits antimicrobial activities. Our previous studies show that the peptide LBDv, synthesized based on the modified sequence of LBD (named LBD2) from FcALF2, exhibited an apparently enhanced antimicrobial activity. To learn the prospect of LBDv application, the characteristics of LBDv were analyzed in the present study. The LBDv peptide showed higher antimicrobial and bactericidal activities compared with LBD2. These activities of the LBDv peptide were stable after heat treatment. LBDv could also exhibit in vivo antimicrobial activity to Vibrio harveyi. The LBDv peptide was found to bind bacteria, quickly cause bacterial agglutination, and kill bacteria by damaging their membrane integrity. Structure analysis showed that both LBDv and LBD2 held the β-sheet structure, and the positive net charge and amphipathicity characteristic were speculated as two important components for their antimicrobial activity. The cytotoxicity of LBDv was evaluated in cultured Spodoptera frugiperda (Sf9) cells and Cherax quadricarinatus hemocytes. More than 80% cells could survive with the LBDv concentration up to 16 μM. Collectively, these findings highlighted the potential antimicrobial mechanism of LBD peptides, and provided important information for the commercial use of LBDv in the future. Full article
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Open AccessFeature PaperReview Bioprospecting Sponge-Associated Microbes for Antimicrobial Compounds
Mar. Drugs 2016, 14(5), 87; doi:10.3390/md14050087
Received: 29 February 2016 / Revised: 15 April 2016 / Accepted: 26 April 2016 / Published: 2 May 2016
Cited by 1 | PDF Full-text (2278 KB) | HTML Full-text | XML Full-text
Abstract
Sponges are the most prolific marine organisms with respect to their arsenal of bioactive compounds including antimicrobials. However, the majority of these substances are probably not produced by the sponge itself, but rather by bacteria or fungi that are associated with their host.
[...] Read more.
Sponges are the most prolific marine organisms with respect to their arsenal of bioactive compounds including antimicrobials. However, the majority of these substances are probably not produced by the sponge itself, but rather by bacteria or fungi that are associated with their host. This review for the first time provides a comprehensive overview of antimicrobial compounds that are known to be produced by sponge-associated microbes. We discuss the current state-of-the-art by grouping the bioactive compounds produced by sponge-associated microorganisms in four categories: antiviral, antibacterial, antifungal and antiprotozoal compounds. Based on in vitro activity tests, identified targets of potent antimicrobial substances derived from sponge-associated microbes include: human immunodeficiency virus 1 (HIV-1) (2-undecyl-4-quinolone, sorbicillactone A and chartarutine B); influenza A (H1N1) virus (truncateol M); nosocomial Gram positive bacteria (thiopeptide YM-266183, YM-266184, mayamycin and kocurin); Escherichia coli (sydonic acid), Chlamydia trachomatis (naphthacene glycoside SF2446A2); Plasmodium spp. (manzamine A and quinolone 1); Leishmania donovani (manzamine A and valinomycin); Trypanosoma brucei (valinomycin and staurosporine); Candida albicans and dermatophytic fungi (saadamycin, 5,7-dimethoxy-4-p-methoxylphenylcoumarin and YM-202204). Thirty-five bacterial and 12 fungal genera associated with sponges that produce antimicrobials were identified, with Streptomyces, Pseudovibrio, Bacillus, Aspergillus and Penicillium as the prominent producers of antimicrobial compounds. Furthemore culture-independent approaches to more comprehensively exploit the genetic richness of antimicrobial compound-producing pathways from sponge-associated bacteria are addressed. Full article
Open AccessArticle Cytotoxic Compounds from the Saudi Red Sea Sponge Xestospongia testudinaria
Mar. Drugs 2016, 14(5), 82; doi:10.3390/md14050082
Received: 4 April 2016 / Revised: 20 April 2016 / Accepted: 21 April 2016 / Published: 26 April 2016
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Abstract
Bioassay-guided fractionation of the organic extract of the Red Sea sponge Xestospongia testudinaria led to the isolation of 13 compounds including two new sterol esters, xestosterol palmitate (2) and xestosterol ester of l6′-bromo-(7′E,11′E,l5′E)-hexadeca-7′,11′,l5′-triene-5′,13′-diynoic acid (4), together with
[...] Read more.
Bioassay-guided fractionation of the organic extract of the Red Sea sponge Xestospongia testudinaria led to the isolation of 13 compounds including two new sterol esters, xestosterol palmitate (2) and xestosterol ester of l6′-bromo-(7′E,11′E,l5′E)-hexadeca-7′,11′,l5′-triene-5′,13′-diynoic acid (4), together with eleven known compounds: xestosterol (1), xestosterol ester of 18′-bromooctadeca-7′E,9′E-diene-7′,15′-diynoic acid (3), and the brominated acetylenic fatty acid derivatives, (5E,11E,15E,19E)-20-bromoeicosa-5,11,15,19-tetraene-9,17-diynoic acid (5), 18,18-dibromo-(9E)-octadeca-9,17-diene-5,7-diynoic acid (6), 18-bromooctadeca-(9E,17E)-diene-7,15-diynoic acid (7), 18-bromooctadeca-(9E,13E,17E)-triene-7,15-diynoic acid (8), l6-bromo (7E,11E,l5E)hexadeca-7,11,l5-triene-5,13-diynoic acid (9), 2-methylmaleimide-5-oxime (10), maleimide-5-oxime (11), tetillapyrone (12), and nortetillapyrone (13). The chemical structures of the isolated compounds were accomplished using one- and two-dimensional NMR, infrared and high-resolution electron impact mass spectroscopy (1D, 2D NMR, IR and HREIMS), and by comparison with the data of the known compounds. The total alcoholic and n-hexane extracts showed remarkable cytotoxic activity against human cervical cancer (HeLa), human hepatocellular carcinoma (HepG-2), and human medulloblastoma (Daoy) cancer cell lines. Interestingly, the dibrominated C18-acetylenic fatty acid (6) exhibited the most potent growth inhibitory activity against these cancer cell lines followed by Compounds 7 and 9. Apparently, the dibromination of the terminal olefinic moiety has an enhanced effect on the cytotoxic activity. Full article
Open AccessReview Polycyclic Guanidine Alkaloids from Poecilosclerida Marine Sponges
Mar. Drugs 2016, 14(4), 77; doi:10.3390/md14040077
Received: 2 February 2016 / Revised: 26 March 2016 / Accepted: 1 April 2016 / Published: 9 April 2016
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Abstract
Sessile marine sponges provide an abundance of unique and diversified scaffolds. In particular, marine guanidine alkaloids display a very wide range of biological applications. A large number of cyclic guanidine alkaloids, including crambines, crambescins, crambescidins, batzelladines or netamins have been isolated from Poecilosclerida
[...] Read more.
Sessile marine sponges provide an abundance of unique and diversified scaffolds. In particular, marine guanidine alkaloids display a very wide range of biological applications. A large number of cyclic guanidine alkaloids, including crambines, crambescins, crambescidins, batzelladines or netamins have been isolated from Poecilosclerida marine sponges. In this review, we will explore the chemodiversity of tri- and pentacyclic guanidine alkaloids. NMR and MS data tools will also be provided, and an overview of the wide range of bioactivities of crambescidins and batzelladines derivatives will be given. Full article
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Open AccessReview Chemical Diversity and Biological Properties of Secondary Metabolites from Sea Hares of Aplysia Genus
Mar. Drugs 2016, 14(2), 39; doi:10.3390/md14020039
Received: 23 December 2015 / Revised: 3 February 2016 / Accepted: 5 February 2016 / Published: 19 February 2016
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Abstract
The marine environment is an important source of structurally-diverse and biologically-active secondary metabolites. During the last two decades, thousands of compounds were discovered in marine organisms, several of them having inspired the development of new classes of therapeutic agents. Marine mollusks constitute a
[...] Read more.
The marine environment is an important source of structurally-diverse and biologically-active secondary metabolites. During the last two decades, thousands of compounds were discovered in marine organisms, several of them having inspired the development of new classes of therapeutic agents. Marine mollusks constitute a successful phyla in the discovery of new marine natural products (MNPs). Over a 50-year period from 1963, 116 genera of mollusks contributed innumerous compounds, Aplysia being the most studied genus by MNP chemists. This genus includes 36 valid species and should be distinguished from all mollusks as it yielded numerous new natural products. Aplysia sea hares are herbivorous mollusks, which have been proven to be a rich source of secondary metabolites, mostly of dietary origin. The majority of secondary metabolites isolated from sea hares of the genus Aplysia are halogenated terpenes; however, these animals are also a source of compounds from other chemical classes, such as macrolides, sterols and alkaloids, often exhibiting cytotoxic, antibacterial, antifungal, antiviral and/or antifeedant activities. This review focuses on the diverse structural classes of secondary metabolites found in Aplysia spp., including several compounds with pronounced biological properties. Full article
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2014

Jump to: 2016, 2013

Open AccessArticle New Briarane Diterpenoids from Taiwanese Soft Coral Briareum violacea
Mar. Drugs 2014, 12(8), 4677-4692; doi:10.3390/md12084677
Received: 28 May 2014 / Revised: 24 July 2014 / Accepted: 24 July 2014 / Published: 22 August 2014
Cited by 3 | PDF Full-text (1198 KB) | HTML Full-text | XML Full-text
Abstract
Ten new briarane diterpenoids, briaviolides A–J (110), together with six known briaranes, solenolides A and D, excavatolide A, briaexcavatolide I, 4β-acetoxy-9-deacetystylatulide lactone and 9-deacetylstylatulide lactone, were isolated from the Taiwanese soft coral, Briareum violacea. Their structures were determined
[...] Read more.
Ten new briarane diterpenoids, briaviolides A–J (110), together with six known briaranes, solenolides A and D, excavatolide A, briaexcavatolide I, 4β-acetoxy-9-deacetystylatulide lactone and 9-deacetylstylatulide lactone, were isolated from the Taiwanese soft coral, Briareum violacea. Their structures were determined on the basis of spectroscopic data (1H- and 13C-NMR, 1H–1H COSY, HSQC, HMBC and NOESY), HR-MS and chemical methods. The absolute configuration of briaviolide A (1) was determined by X-ray crystallographic analysis. Compounds 5, 9 and derivative 11 showed moderate inhibitory activities on superoxide-anion generation and elastase release by human neutrophils in response to N-formyl-methionyl-leucyl-phenylalanine/ Cytochalasin B (fMLP/CB). Full article
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Open AccessArticle Structural Elucidation of Novel Saponins in the Sea Cucumber Holothuria lessoni
Mar. Drugs 2014, 12(8), 4439-4473; doi:10.3390/md12084439
Received: 5 June 2014 / Revised: 25 July 2014 / Accepted: 25 July 2014 / Published: 8 August 2014
Cited by 7 | PDF Full-text (2067 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Sea cucumbers are prolific producers of a wide range of bioactive compounds. This study aimed to purify and characterize one class of compound, the saponins, from the viscera of the Australian sea cucumber Holothuria lessoni. The saponins were obtained by ethanolic extraction
[...] Read more.
Sea cucumbers are prolific producers of a wide range of bioactive compounds. This study aimed to purify and characterize one class of compound, the saponins, from the viscera of the Australian sea cucumber Holothuria lessoni. The saponins were obtained by ethanolic extraction of the viscera and enriched by a liquid-liquid partition process and adsorption column chromatography. A high performance centrifugal partition chromatography (HPCPC) was applied to the saponin-enriched mixture to obtain saponins with high purity. The resultant purified saponins were profiled using MALDI-MS/MS and ESI-MS/MS which revealed the structure of isomeric saponins to contain multiple aglycones and/or sugar residues. We have elucidated the structure of five novel saponins, Holothurins D/E and Holothurinosides X/Y/Z, along with seven reported triterpene glycosides, including sulfated and non-sulfated saponins containing a range of aglycones and sugar moieties, from the viscera of H. lessoni. The abundance of novel compounds from this species holds promise for biotechnological applications. Full article
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Open AccessArticle Cytotoxic and Apoptosis-Inducing Activity of Triterpene Glycosides from Holothuria scabra and Cucumaria frondosa against HepG2 Cells
Mar. Drugs 2014, 12(8), 4274-4290; doi:10.3390/md12084274
Received: 9 February 2014 / Revised: 4 April 2014 / Accepted: 8 April 2014 / Published: 24 July 2014
Cited by 6 | PDF Full-text (1099 KB) | HTML Full-text | XML Full-text
Abstract
The cytotoxic effects of thirteen triterpene glycosides from Holothuria scabra Jaeger and Cucumaria frondosa Gunnerus (Holothuroidea) against four human cell lines were detected and their cytotoxicity-structure relationships were established. The apoptosis-inducing activity of a more potent glycoside echinoside A (1) in
[...] Read more.
The cytotoxic effects of thirteen triterpene glycosides from Holothuria scabra Jaeger and Cucumaria frondosa Gunnerus (Holothuroidea) against four human cell lines were detected and their cytotoxicity-structure relationships were established. The apoptosis-inducing activity of a more potent glycoside echinoside A (1) in HepG2 cells was further investigated by determining its effect on the morphology, mitochondrial transmembrane potential (Δψm) and mRNA expression levels of the apoptosis-related genes. The results showed that the number of glycosyl residues in sugar chains and the side chain of aglycone could affect their cytotoxicity towards tumor cells and selective cytotoxicity. 1 significantly inhibited cell viability and induced apoptosis in HepG2 cells. 1 also markedly decreased the Δψm and Bcl-2/Bax mRNA express ratio, and up-regulated the mRNA expression levels of Caspase-3, Caspase-8 and Caspase-9 in HepG2 cells. Therefore, 1 induced apoptosis in HepG2 cells through both intrinsic and extrinsic pathway. These findings could potentially promote the usage of these glycosides as leading compounds for developing new antitumor drugs. Full article
Open AccessArticle Ovothiol Isolated from Sea Urchin Oocytes Induces Autophagy in the Hep-G2 Cell Line
Mar. Drugs 2014, 12(7), 4069-4085; doi:10.3390/md12074069
Received: 1 April 2014 / Revised: 11 June 2014 / Accepted: 23 June 2014 / Published: 7 July 2014
Cited by 7 | PDF Full-text (584 KB) | HTML Full-text | XML Full-text
Abstract
Ovothiols are histidine-derived thiols isolated from sea urchin eggs, where they play a key role in the protection of cells toward the oxidative burst associated with fertilization by controlling the cellular redox balance and recycling oxidized glutathione. In this study, we show that
[...] Read more.
Ovothiols are histidine-derived thiols isolated from sea urchin eggs, where they play a key role in the protection of cells toward the oxidative burst associated with fertilization by controlling the cellular redox balance and recycling oxidized glutathione. In this study, we show that treatment of a human liver carcinoma cell line, Hep-G2, with ovothiol A, isolated from Paracentrotus lividus oocytes, results in a decrease of cell proliferation in a dose-dependent manner. The activation of an autophagic process is revealed by phase contrast and fluorescence microscopy, together with the expression of the specific autophagic molecular markers, LC3 II and Beclin-1. The effect of ovothiol is not due to its antioxidant capacity or to hydrogen peroxide generation. The concentration of ovothiol A in the culture media, as monitored by HPLC analysis, decreased by about 24% within 30 min from treatment. The proliferation of normal human embryonic lung cells is not affected by ovothiol A. These results hint at ovothiol as a promising bioactive molecule from marine organisms able to inhibit cell proliferation in cancer cells. Full article
Open AccessArticle Bioactive Cembrane Derivatives from the Indian Ocean Soft Coral, Sinularia kavarattiensis
Mar. Drugs 2014, 12(7), 4045-4068; doi:10.3390/md12074045
Received: 1 April 2014 / Revised: 5 June 2014 / Accepted: 17 June 2014 / Published: 3 July 2014
Cited by 5 | PDF Full-text (1559 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Marine organisms and their metabolites represent a unique source of potential pharmaceutical substances. In this study, we examined marine-derived substances for their bioactive properties in a cell-based Chikungunya virus (CHIKV) replicon model and for in vitro anti-inflammatory activity. In the screening of a
[...] Read more.
Marine organisms and their metabolites represent a unique source of potential pharmaceutical substances. In this study, we examined marine-derived substances for their bioactive properties in a cell-based Chikungunya virus (CHIKV) replicon model and for in vitro anti-inflammatory activity. In the screening of a marine sample library, crude extracts from the Indian soft coral, Sinularia kavarattiensis, showed promising activity against the CHIKV replicon. Bioassay-guided chemical fractionation of S. kavarattiensis resulted in the isolation of six known norcembranoids (16) and one new compound, named kavaranolide (7). The structures were elucidated on the basis of NMR and MS spectroscopic data. Compounds 13 and 57 were evaluated for their replicon-inhibiting potential in the CHIKV model by using a luminescence-based detection technique and live cell imaging. Compounds 1 and 2 showed moderate inhibition of the CHIKV replicon, but imaging studies also revealed cytotoxic properties. Moreover, the effects of the isolated compounds on primary microglial cells, an experimental model for neuroinflammation, were evaluated. Compound 2 was shown to modulate the immune response in microglial cells and to possess potential anti-inflammatory properties by dose-dependently reducing the release of pro- and anti-inflammatory cytokines. Full article
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Open AccessArticle Flexibilide Obtained from Cultured Soft Coral Has Anti-Neuroinflammatory and Analgesic Effects through the Upregulation of Spinal Transforming Growth Factor-β1 in Neuropathic Rats
Mar. Drugs 2014, 12(7), 3792-3817; doi:10.3390/md12073792
Received: 8 April 2014 / Revised: 28 May 2014 / Accepted: 29 May 2014 / Published: 27 June 2014
Cited by 14 | PDF Full-text (628 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Chronic neuroinflammation plays an important role in the development and maintenance of neuropathic pain. The compound flexibilide, which can be obtained from cultured soft coral, possesses anti-inflammatory and analgesic effects in the rat carrageenan peripheral inflammation model. In the present study, we investigated
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Chronic neuroinflammation plays an important role in the development and maintenance of neuropathic pain. The compound flexibilide, which can be obtained from cultured soft coral, possesses anti-inflammatory and analgesic effects in the rat carrageenan peripheral inflammation model. In the present study, we investigated the antinociceptive properties of flexibilide in the rat chronic constriction injury (CCI) model of neuropathic pain. First, we found that a single intrathecal (i.t.) administration of flexibilide significantly attenuated CCI-induced thermal hyperalgesia at 14 days after surgery. Second, i.t. administration of 10-μg flexibilide twice daily was able to prevent the development of thermal hyperalgesia and weight-bearing deficits in CCI rats. Third, i.t. flexibilide significantly inhibited CCI-induced activation of microglia and astrocytes, as well as the upregulated proinflammatory enzyme, inducible nitric oxide synthase, in the ipsilateral spinal dorsal horn. Furthermore, flexibilide attenuated the CCI-induced downregulation of spinal transforming growth factor-β1 (TGF-β1) at 14 days after surgery. Finally, i.t. SB431542, a selective inhibitor of TGF-β type I receptor, blocked the analgesic effects of flexibilide in CCI rats. Our results suggest that flexibilide may serve as a therapeutic agent for neuropathic pain. In addition, spinal TGF-β1 may be involved in the anti-neuroinflammatory and analgesic effects of flexibilide. Full article
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Open AccessArticle Defensive Metabolites from Antarctic Invertebrates: Does Energetic Content Interfere with Feeding Repellence?
Mar. Drugs 2014, 12(6), 3770-3791; doi:10.3390/md12063770
Received: 1 April 2014 / Revised: 23 May 2014 / Accepted: 29 May 2014 / Published: 24 June 2014
Cited by 4 | PDF Full-text (789 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Many bioactive products from benthic invertebrates mediating ecological interactions have proved to reduce predation, but their mechanisms of action, and their molecular identities, are usually unknown. It was suggested, yet scarcely investigated, that nutritional quality interferes with defensive metabolites. This means that antifeedants
[...] Read more.
Many bioactive products from benthic invertebrates mediating ecological interactions have proved to reduce predation, but their mechanisms of action, and their molecular identities, are usually unknown. It was suggested, yet scarcely investigated, that nutritional quality interferes with defensive metabolites. This means that antifeedants would be less effective when combined with energetically rich prey, and that higher amounts of defensive compounds would be needed for predator avoidance. We evaluated the effects of five types of repellents obtained from Antarctic invertebrates, in combination with diets of different energetic values. The compounds came from soft corals, ascidians and hexactinellid sponges; they included wax esters, alkaloids, a meroterpenoid, a steroid, and the recently described organic acid, glassponsine. Feeding repellency was tested through preference assays by preparing diets (alginate pearls) combining different energetic content and inorganic material. Experimental diets contained various concentrations of each repellent product, and were offered along with control compound-free pearls, to the Antarctic omnivore amphipod Cheirimedon femoratus. Meridianin alkaloids were the most active repellents, and wax esters were the least active when combined with foods of distinct energetic content. Our data show that levels of repellency vary for each compound, and that they perform differently when mixed with distinct assay foods. The natural products that interacted the most with energetic content were those occurring in nature at higher concentrations. The bioactivity of the remaining metabolites tested was found to depend on a threshold concentration, enough to elicit feeding repellence, independently from nutritional quality. Full article
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Open AccessReview Quinone and Hydroquinone Metabolites from the Ascidians of the Genus Aplidium
Mar. Drugs 2014, 12(6), 3608-3633; doi:10.3390/md12063608
Received: 1 April 2014 / Revised: 3 June 2014 / Accepted: 4 June 2014 / Published: 12 June 2014
Cited by 4 | PDF Full-text (2024 KB) | HTML Full-text | XML Full-text
Abstract
Ascidians of the genus Aplidium are recognized as an important source of chemical diversity and bioactive natural products. Among the compounds produced by this genus are non-nitrogenous metabolites, mainly prenylated quinones and hydroquinones. This review discusses the isolation, structural elucidation, and biological activities
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Ascidians of the genus Aplidium are recognized as an important source of chemical diversity and bioactive natural products. Among the compounds produced by this genus are non-nitrogenous metabolites, mainly prenylated quinones and hydroquinones. This review discusses the isolation, structural elucidation, and biological activities of quinones, hydroquinones, rossinones, longithorones, longithorols, floresolides, scabellones, conicaquinones, aplidinones, thiaplidiaquinones, and conithiaquinones. A compilation of the 13C-NMR spectral data of these compounds is also presented. Full article
Open AccessReview Conotoxins Targeting Nicotinic Acetylcholine Receptors: An Overview
Mar. Drugs 2014, 12(5), 2970-3004; doi:10.3390/md12052970
Received: 31 March 2014 / Revised: 24 April 2014 / Accepted: 28 April 2014 / Published: 22 May 2014
Cited by 27 | PDF Full-text (2428 KB) | HTML Full-text | XML Full-text
Abstract
Marine snails of the genus Conus are a large family of predatory gastropods with an unparalleled molecular diversity of pharmacologically active compounds in their venom. Cone snail venom comprises of a rich and diverse cocktail of peptide toxins which act on a wide
[...] Read more.
Marine snails of the genus Conus are a large family of predatory gastropods with an unparalleled molecular diversity of pharmacologically active compounds in their venom. Cone snail venom comprises of a rich and diverse cocktail of peptide toxins which act on a wide variety of ion channels such as voltage-gated sodium- (NaV), potassium- (KV), and calcium- (CaV) channels as well as nicotinic acetylcholine receptors (nAChRs) which are classified as ligand-gated ion channels. The mode of action of several conotoxins has been the subject of investigation, while for many others this remains unknown. This review aims to give an overview of the knowledge we have today on the molecular pharmacology of conotoxins specifically interacting with nAChRs along with the structure–function relationship data. Full article
Open AccessCommunication Isolation and Identification of Antitrypanosomal and Antimycobacterial Active Steroids from the Sponge Haliclona simulans
Mar. Drugs 2014, 12(5), 2937-2952; doi:10.3390/md12052937
Received: 30 January 2014 / Revised: 25 April 2014 / Accepted: 28 April 2014 / Published: 16 May 2014
Cited by 9 | PDF Full-text (1163 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The marine sponge Haliclona simulans collected from the Irish Sea yielded two new steroids: 24-vinyl-cholest-9-ene-3β,24-diol and 20-methyl-pregn-6-en-3β-ol,5a,8a-epidioxy, along with the widely distributed 24-methylenecholesterol. One of the steroids possesses an unusually short hydrocarbon side chain. The structures were elucidated using nuclear magnetic resonance spectroscopy
[...] Read more.
The marine sponge Haliclona simulans collected from the Irish Sea yielded two new steroids: 24-vinyl-cholest-9-ene-3β,24-diol and 20-methyl-pregn-6-en-3β-ol,5a,8a-epidioxy, along with the widely distributed 24-methylenecholesterol. One of the steroids possesses an unusually short hydrocarbon side chain. The structures were elucidated using nuclear magnetic resonance spectroscopy and confirmed using electron impact- and high resolution electrospray-mass spectrometry. All three steroids possess antitrypanosomal and anti-mycobacterial activity. All the steroids were found to possess low cytotoxicity against Hs27 which was above their detected antitrypanosomal potent concentrations. Full article
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Open AccessReview Cephalopod Ink: Production, Chemistry, Functions and Applications
Mar. Drugs 2014, 12(5), 2700-2730; doi:10.3390/md12052700
Received: 14 March 2014 / Revised: 10 April 2014 / Accepted: 14 April 2014 / Published: 12 May 2014
Cited by 13 | PDF Full-text (3686 KB) | HTML Full-text | XML Full-text
Abstract
One of the most distinctive and defining features of coleoid cephalopods—squid, cuttlefish and octopus—is their inking behavior. Their ink, which is blackened by melanin, but also contains other constituents, has been used by humans in various ways for millennia. This review summarizes our
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One of the most distinctive and defining features of coleoid cephalopods—squid, cuttlefish and octopus—is their inking behavior. Their ink, which is blackened by melanin, but also contains other constituents, has been used by humans in various ways for millennia. This review summarizes our current knowledge of cephalopod ink. Topics include: (1) the production of ink, including the functional organization of the ink sac and funnel organ that produce it; (2) the chemical components of ink, with a focus on the best known of these—melanin and the biochemical pathways involved in its production; (3) the neuroecology of the use of ink in predator-prey interactions by cephalopods in their natural environment; and (4) the use of cephalopod ink by humans, including in the development of drugs for biomedical applications and other chemicals for industrial and other commercial applications. As is hopefully evident from this review, much is known about cephalopod ink and inking, yet more striking is how little we know. Towards closing that gap, future directions in research on cephalopod inking are suggested. Full article
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Open AccessReview Pathophysiological Effects of Synthetic Derivatives of Polymeric Alkylpyridinium Salts from the Marine Sponge, Reniera sarai
Mar. Drugs 2014, 12(5), 2408-2421; doi:10.3390/md12052408
Received: 17 March 2014 / Revised: 4 April 2014 / Accepted: 4 April 2014 / Published: 30 April 2014
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Abstract
Polymeric 3-alkylpyridinium salts (poly-APS) are among the most studied natural bioactive compounds extracted from the marine sponge, Reniera sarai. They exhibit a wide range of biological activities, and the most prominent among them are the anti-acetylcholinesterase and membrane-damaging activity. Due to their
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Polymeric 3-alkylpyridinium salts (poly-APS) are among the most studied natural bioactive compounds extracted from the marine sponge, Reniera sarai. They exhibit a wide range of biological activities, and the most prominent among them are the anti-acetylcholinesterase and membrane-damaging activity. Due to their membrane activity, sAPS can induce the lysis of various cells and cell lines and inhibit the growth of bacteria and fungi. Because of their bioactivity, poly-APS are possible candidates for use in the fields of medicine, pharmacy and industry. Due to the small amounts of naturally occurring poly-APS, methods for the synthesis of analogues have been developed. They differ in chemical properties, such as the degree of polymerization, the length of the alkyl chains (from three to 12 carbon atoms) and in the counter ions present in their structures. Such structurally defined analogues with different chemical properties and degrees of polymerization possess different levels of biological activity. We review the current knowledge of the biological activity and toxicity of synthetic poly-APS analogues, with particular emphasis on the mechanisms of their physiological and pharmacological effects and, in particular, the mechanisms of toxicity of two analogues, APS12-2 and APS3, in vivo and in vitro. Full article
Open AccessArticle Eunicellin-Based Diterpenoids, Hirsutalins N–R, from the Formosan Soft Coral Cladiella hirsuta
Mar. Drugs 2014, 12(5), 2446-2457; doi:10.3390/md12052446
Received: 13 February 2014 / Revised: 24 March 2014 / Accepted: 31 March 2014 / Published: 30 April 2014
Cited by 9 | PDF Full-text (777 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
New eunicellin-type hirsutalins N–R (15), along with two known eunicellins, (6 and 7) were isolated from the soft coral Cladiella hirsuta. The structures of the metabolites were determined by extensive spectroscopic analysis. Cytotoxic activity of compounds
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New eunicellin-type hirsutalins N–R (15), along with two known eunicellins, (6 and 7) were isolated from the soft coral Cladiella hirsuta. The structures of the metabolites were determined by extensive spectroscopic analysis. Cytotoxic activity of compounds 17 against the proliferation of a limited panel of cancer cell lines was measured. The in vitro anti-inflammatory activity of compounds 17 was evaluated by measuring their ability in suppressing superoxide anion generation and elastase release in fMLP/CB-induced human neutrophils. Full article
Open AccessArticle Pelagia noctiluca (Scyphozoa) Crude Venom Injection Elicits Oxidative Stress and Inflammatory Response in Rats
Mar. Drugs 2014, 12(4), 2182-2204; doi:10.3390/md12042182
Received: 23 January 2014 / Revised: 20 March 2014 / Accepted: 21 March 2014 / Published: 10 April 2014
Cited by 9 | PDF Full-text (1301 KB) | HTML Full-text | XML Full-text
Abstract
Cnidarian toxins represent a rich source of biologically active compounds. Since they may act via oxidative stress events, the aim of the present study was to verify whether crude venom, extracted from the jellyfish Pelagia noctiluca, elicits inflammation and oxidative stress processes,
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Cnidarian toxins represent a rich source of biologically active compounds. Since they may act via oxidative stress events, the aim of the present study was to verify whether crude venom, extracted from the jellyfish Pelagia noctiluca, elicits inflammation and oxidative stress processes, known to be mediated by Reactive Oxygen Species (ROS) production, in rats. In a first set of experiments, the animals were injected with crude venom (at three different doses 6, 30 and 60 µg/kg, suspended in saline solution, i.v.) to test the mortality and possible blood pressure changes. In a second set of experiments, to confirm that Pelagia noctiluca crude venom enhances ROS formation and may contribute to the pathophysiology of inflammation, crude venom-injected animals (30 µg/kg) were also treated with tempol, a powerful antioxidant (100 mg/kg i.p., 30 and 60 min after crude venom). Administration of tempol after crude venom challenge, caused a significant reduction of each parameter related to inflammation. The potential effect of Pelagia noctiluca crude venom in the systemic inflammation process has been here demonstrated, adding novel information about its biological activity. Full article
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Open AccessArticle Insights and Ideas Garnered from Marine Metabolites for Development of Dual-Function Acetylcholinesterase and Amyloid-β Aggregation Inhibitors
Mar. Drugs 2014, 12(4), 2114-2131; doi:10.3390/md12042114
Received: 10 December 2013 / Revised: 27 February 2014 / Accepted: 12 March 2014 / Published: 4 April 2014
Cited by 4 | PDF Full-text (2061 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Due to the diversity of biological activities that can be found in aquatic ecosystems, marine metabolites have been an active area of drug discovery for the last 30 years. Marine metabolites have been found to inhibit a number of enzymes important in the
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Due to the diversity of biological activities that can be found in aquatic ecosystems, marine metabolites have been an active area of drug discovery for the last 30 years. Marine metabolites have been found to inhibit a number of enzymes important in the treatment of human disease. Here, we focus on marine metabolites that inhibit the enzyme acetylcholinesterase, which is the cellular target for treatment of early-stage Alzheimer’s disease. Currently, development of anticholinesterase drugs with improved potency, and drugs that act as dual acetylcholinesterase and amyloid-β aggregation inhibitors, are being sought to treat Alzheimer’s disease. Seven classes of marine metabolites are reported to possess anti-cholinesterase activity. We compared these metabolites to clinically-used acetylcholinesterase inhibitors having known mechanisms of inhibition. We performed a docking simulation and compared them to published experimental data for each metabolite to determine the most likely mechanism of inhibition for each class of marine inhibitor. Our results indicate that several marine metabolites bind to regions of the acetylcholinesterase active site that are not bound by the clinically-used drugs rivastigmine, galanthamine, donepezil, or tacrine. We use the novel poses adopted for computational drug design of tighter binding anticholinesterase drugs likely to act as inhibitors of both acetylcholinesterase activity and amyloid-β aggregation inhibition. Full article
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Open AccessArticle Neritinaceramides A–E, New Ceramides from the Marine Bryozoan Bugula neritina Inhabiting South China Sea and Their Cytotoxicity
Mar. Drugs 2014, 12(4), 1987-2003; doi:10.3390/md12041987
Received: 23 January 2014 / Revised: 2 March 2014 / Accepted: 13 March 2014 / Published: 2 April 2014
Cited by 4 | PDF Full-text (970 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Five new ceramides, neritinaceramides A (1), B (2), C (3), D (4) and E (5), together with six known ceramides (611), two known alkyl glycerylethers (12 and 13
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Five new ceramides, neritinaceramides A (1), B (2), C (3), D (4) and E (5), together with six known ceramides (611), two known alkyl glycerylethers (12 and 13) and a known nucleoside (14), were isolated from marine bryozoan Bugula neritina, which inhabits the South China Sea. The structures of the new compounds were elucidated as (2S,3R,3′S,4E,8E,10E)-2-(hexadecanoylamino)-4,8,10-octadecatriene-l,3,3′-triol (1), (2S,3R,2′R,4E,8E,10E)-2-(hexadecanoylamino)-4,8,10-octadecatriene-l,3,2′-triol (2), (2S,3R,2′R,4E,8E,10E)-2-(octadecanoylamino)-4,8,10-octadecatriene-l,3,2′-triol (3), (2S,3R,3′S,4E,8E)-2-(hexadecanoylamino)-4,8-octadecadiene-l,3,3′-triol (4) and (2S,3R,3′S,4E)-2-(hexadecanoylamino)-4-octadecene-l,3,3′-triol (5) on the basis of extensive spectral analysis and chemical evidences. The characteristic C-3′S hydroxyl group in the fatty acid moiety in compounds 1, 4 and 5, was a novel structural feature of ceramides. The rare 4E,8E,10E-triene structure in the sphingoid base of compounds 13, was found from marine bryozoans for the first time. The new ceramides 15 were evaluated for their cytotoxicity against HepG2, NCI-H460 and SGC7901 tumor cell lines, and all of them exhibited selective cytotoxicity against HepG2 and SGC7901 cells with a range of IC50 values from 47.3 μM to 58.1 μM. These chemical and cytotoxic studies on the new neritinaceramides A–E (15) added to the chemical diversity of B. neritina and expanded our knowledge of the chemical modifications and biological activity of ceramides. Full article
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Open AccessArticle Variegatusides: New Non-Sulphated Triterpene Glycosides from the Sea Cucumber Stichopus variegates Semper
Mar. Drugs 2014, 12(4), 2004-2018; doi:10.3390/md12042004
Received: 11 December 2013 / Revised: 29 January 2014 / Accepted: 7 February 2014 / Published: 2 April 2014
Cited by 6 | PDF Full-text (907 KB) | HTML Full-text | XML Full-text
Abstract
Four new triterpene glycosides, variegatusides C–F (14), together with three structurally known triterpene glycosides, variegatusides A and B (5, 6), and holothurin B (7), were isolated from the sea cucumber Stichopus variegates Semper (Holothuriidae),
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Four new triterpene glycosides, variegatusides C–F (14), together with three structurally known triterpene glycosides, variegatusides A and B (5, 6), and holothurin B (7), were isolated from the sea cucumber Stichopus variegates Semper (Holothuriidae), collected from the South China Sea. Their structures were elucidated on the basis of extensive spectral analysis (nuclear magnetic resonance (NMR) and electrospray ionization mass spectrometry (ESIMS)) and chemical evidence. Variegatusides C–F exhibit the same structural feature consisting of the presence of a 23-hydroxyl group at the holostane-type triterpene aglycone side chain. Variegatuside C (1) has a double bond (24, 25) in this same chain, while variegatuside D (2) exhibits a 8(9)-ene bond in the holostane-type triterpene aglycone, which has not been extracted from other sea cucumber species. Compound 4 is a native compound from the sea cucumber S. variegates Semper, which has been reported to be desacetylstichloroside B1. Except for holothurin B, these glycosides have no sulfate group in their sugar chain and show potent antifungal activities in vitro biotests. Full article
Open AccessCommunication Ochracenoids A and B, Guaiazulene-Based Analogues from Gorgonian Anthogorgia ochracea Collected from the South China Sea
Mar. Drugs 2014, 12(3), 1569-1579; doi:10.3390/md12031569
Received: 24 December 2013 / Revised: 15 January 2014 / Accepted: 6 February 2014 / Published: 14 March 2014
Cited by 5 | PDF Full-text (797 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two new guaiazulene-based analogues, ochracenoids A (1) and B (2), along with four known analogues (36), were isolated from the gorgonian Anthogorgia ochracea collected from the South China Sea. The planar structures of the new
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Two new guaiazulene-based analogues, ochracenoids A (1) and B (2), along with four known analogues (36), were isolated from the gorgonian Anthogorgia ochracea collected from the South China Sea. The planar structures of the new compounds were elucidated by comprehensive spectroscopic data. The absolute configuration of 1 was determined as 3R by the comparison of TDDFT calculated electronic circular dichroism with its experimental spectrum. Compound 1 is a rare guaiazulene-based analogue possessing a unique C16 skeleton. The possible generation process of 1 through an intermolecular one-carbon-transfer reaction was also discussed. Compound 2 was previously described as a presumed intermediate involved in the biogenesis of anthogorgienes A and I. Compound 3 exhibited antiproliferative effects on the embryo development of zebrafish Danio rerio. Full article
Open AccessArticle Bioactive Cembranoids, Sarcocrassocolides P–R, from the Dongsha Atoll Soft Coral Sarcophyton crassocaule
Mar. Drugs 2014, 12(2), 840-850; doi:10.3390/md12020840
Received: 12 November 2013 / Revised: 13 December 2013 / Accepted: 17 January 2014 / Published: 28 January 2014
Cited by 3 | PDF Full-text (921 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
New cembranoids, sarcocrassocolides P–R (13) and four known compounds (47) were isolated from the soft coral Sarcophyton crassocaule. The structures of the metabolites were determined by extensive spectroscopic analysis. Compounds 35 and
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New cembranoids, sarcocrassocolides P–R (13) and four known compounds (47) were isolated from the soft coral Sarcophyton crassocaule. The structures of the metabolites were determined by extensive spectroscopic analysis. Compounds 35 and 7 were shown to exhibit cytotoxicity toward a limited panel of cancer cell lines and all compounds 17 displayed potent in vitro anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells by inhibiting the expression of inducible nitric oxide synthase (iNOS) protein. Compound 7 also showed significant activity in reducing the accumulation of cyclooxygenase-2 (COX-2) protein in the same macrophage cells. Full article
Open AccessCommunication Six New Tetraprenylated Alkaloids from the South China Sea Gorgonian Echinogorgia pseudossapo
Mar. Drugs 2014, 12(2), 672-681; doi:10.3390/md12020672
Received: 25 November 2013 / Revised: 10 December 2013 / Accepted: 13 January 2014 / Published: 27 January 2014
Cited by 8 | PDF Full-text (681 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Six new tetraprenylated alkaloids, designated as malonganenones L–Q (16), were isolated from the gorgonian Echinogorgia pseudossapo, collected in Daya Bay of Guangdong Province, China. The structures of 16 featuring a methyl group at N-3 and a
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Six new tetraprenylated alkaloids, designated as malonganenones L–Q (16), were isolated from the gorgonian Echinogorgia pseudossapo, collected in Daya Bay of Guangdong Province, China. The structures of 16 featuring a methyl group at N-3 and a tetraprenyl chain at N-7 in the hypoxanthine core were established by extensive spectroscopic analyses. Compounds 16 were tested for their inhibitory activity against the phosphodiesterases (PDEs)-4D, 5A, and 9A, and compounds 1 and 6 exhibited moderate inhibitory activity against PDE4D with IC50 values of 8.5 and 20.3 µM, respectively. Full article
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Open AccessArticle Spongionella Secondary Metabolites Protect Mitochondrial Function in Cortical Neurons against Oxidative Stress
Mar. Drugs 2014, 12(2), 700-718; doi:10.3390/md12020700
Received: 21 November 2013 / Revised: 7 January 2014 / Accepted: 8 January 2014 / Published: 27 January 2014
Cited by 9 | PDF Full-text (1323 KB) | HTML Full-text | XML Full-text
Abstract
The marine habitat provides a large number of structurally-diverse bioactive compounds for drug development. Marine sponges have been studied over many years and are found to be a rich source of these bioactive chemicals. This study is focused on the evaluation of the
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The marine habitat provides a large number of structurally-diverse bioactive compounds for drug development. Marine sponges have been studied over many years and are found to be a rich source of these bioactive chemicals. This study is focused on the evaluation of the activity of six diterpene derivatives isolated from Spongionella sp. on mitochondrial function using an oxidative in vitro stress model. The test compounds include the Gracilins (A, H, K, J and L) and tetrahydroaplysulphurin-1. Compounds were co-incubated with hydrogen peroxide for 12 hours to determine their protective capacities and their effect on markers of apoptosis and Nrf2/ARE pathways was evaluated. Results conclude that Gracilins preserve neurons against oxidative damage, and that in particular, tetrahydroaplysulphurin-1 shows a complete neuroprotective activity. Oxidative stress is linked to mitochondrial dysfunction and consequently to neurodegenerative disorders like Parkinson and Alzheimer diseases, Friedreich ataxia or Amyotrophic lateral sclerosis. This neuroprotection against oxidation conditions suggest that these metabolites could be interesting lead candidates in drug development for neurodegenerative diseases. Full article
Open AccessArticle First Report of a Peroxiredoxin Homologue in Jellyfish: Molecular Cloning, Expression and Functional Characterization of CcPrx4 from Cyanea capillata
Mar. Drugs 2014, 12(1), 214-231; doi:10.3390/md12010214
Received: 19 October 2013 / Revised: 20 December 2013 / Accepted: 23 December 2013 / Published: 9 January 2014
Cited by 4 | PDF Full-text (1335 KB) | HTML Full-text | XML Full-text
Abstract
We first identified and characterized a novel peroxiredoxin (Prx), designated as CcPrx4, from the cDNA library of the tentacle of the jellyfish Cyanea capillata. The full-length cDNA sequence of CcPrx4 consisted of 884 nucleotides with an open reading frame encoding a mature
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We first identified and characterized a novel peroxiredoxin (Prx), designated as CcPrx4, from the cDNA library of the tentacle of the jellyfish Cyanea capillata. The full-length cDNA sequence of CcPrx4 consisted of 884 nucleotides with an open reading frame encoding a mature protein of 247 amino acids. It showed a significant homology to peroxiredoxin 4 (Prx4) with the highly conserved F-motif (93FTFVCPTEI101), hydrophobic region (217VCPAGW222), 140GGLG143 and 239YF240, indicating that it should be a new member of the Prx4 family. The deduced CcPrx4 protein had a calculated molecular mass of 27.2 kDa and an estimated isoelectric point of 6.3. Quantitative real-time PCR analysis showed that CcPrx4 mRNA could be detected in all the jellyfish tissues analyzed. CcPrx4 protein was cloned into the expression vector, pET-24a, and expressed in Escherichia coli Rosetta (DE3) pLysS. Recombinant CcPrx4 protein was purified by HisTrap High Performance chelating column chromatography and analyzed for its biological function. The results showed that the purified recombinant CcPrx4 protein manifested the ability to reduce hydrogen peroxide and protect supercoiled DNA from oxidative damage, suggesting that CcPrx4 protein may play an important role in protecting jellyfish from oxidative damage. Full article
Open AccessReview Holothurian Fucosylated Chondroitin Sulfate
Mar. Drugs 2014, 12(1), 232-254; doi:10.3390/md12010232
Received: 5 November 2013 / Revised: 23 December 2013 / Accepted: 30 December 2013 / Published: 9 January 2014
Cited by 27 | PDF Full-text (668 KB) | HTML Full-text | XML Full-text
Abstract
Fucosylated chondroitin sulfate (FucCS) is a structurally distinct glycosaminoglycan found in sea cucumber species. It has the same backbone composition of alternating 4-linked glucuronic acid and 3-linked N-acetyl galactosamine residues within disaccharide repeating units as regularly found in mammalian chondroitin sulfates. However,
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Fucosylated chondroitin sulfate (FucCS) is a structurally distinct glycosaminoglycan found in sea cucumber species. It has the same backbone composition of alternating 4-linked glucuronic acid and 3-linked N-acetyl galactosamine residues within disaccharide repeating units as regularly found in mammalian chondroitin sulfates. However, FucCS has also sulfated fucosyl branching units 3-O-linked to the acid residues. The sulfation patterns of these branches vary accordingly with holothurian species and account for different biological actions and responses. FucCSs may exhibit anticoagulant, antithrombotic, anti-inflammatory, anticancer, antiviral, and pro-angiogenic activities, besides its beneficial effects in hemodialysis, cellular growth modulation, fibrosis and hyperglycemia. Through an historical overview, this document covers most of the science regarding the holothurian FucCS. Both structural and medical properties of this unique GAG, investigated during the last 25 years, are systematically discussed herein. Full article
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Open AccessArticle Diamond Squid (Thysanoteuthis rhombus)-Derived Chondroitin Sulfate Stimulates Bone Healing within a Rat Calvarial Defect
Mar. Drugs 2013, 11(12), 5024-5035; doi:10.3390/md11125024
Received: 15 October 2013 / Revised: 25 November 2013 / Accepted: 27 November 2013 / Published: 11 December 2013
Cited by 2 | PDF Full-text (967 KB) | HTML Full-text | XML Full-text
Abstract
Chondroitin sulfate (CS) has been suggested to be involved in bone formation and mineralization processes. A previous study showed that squid-derived CS (sqCS) has osteoblastogenesis ability in cooperation with bone morphogenetic protein (BMP)-4 in vitro. However, in vivo, osteogenic potential has
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Chondroitin sulfate (CS) has been suggested to be involved in bone formation and mineralization processes. A previous study showed that squid-derived CS (sqCS) has osteoblastogenesis ability in cooperation with bone morphogenetic protein (BMP)-4 in vitro. However, in vivo, osteogenic potential has not been verified. In this study, we created a critical-sized bone defect in the rat calvaria and implanted sqCS-loaded gelatin hydrogel sponges (Gel) into the defect with or without BMP-4 (CS/BMP/Gel and CS/Gel, respectively). At 15 weeks, bone repair rate of CS/Gel-treated defects and CS/BMP/Gel-treated defects were 47.2% and 51.1%, respectively, whereas empty defects and defects with untreated sponges showed significantly less bone ingrowth. The intensity of von Kossa staining of the regenerated bone was less than that of the original one. Mineral apposition rates at 9 to 10 weeks were not significantly different between all treatment groups. Although bone repair was not completed, sqCS stimulated bone regeneration without BMP-4 and without external mesenchymal cells or preosteoblasts. Therefore, sqCS is a promising substance for promotion of osteogenesis. Full article
Open AccessArticle Cytotoxic, Cytostatic and HIV-1 PR Inhibitory Activities of the Soft Coral Litophyton arboreum
Mar. Drugs 2013, 11(12), 4917-4936; doi:10.3390/md11124917
Received: 24 September 2013 / Revised: 18 November 2013 / Accepted: 19 November 2013 / Published: 10 December 2013
Cited by 7 | PDF Full-text (1308 KB) | HTML Full-text | XML Full-text
Abstract
Bioassay-guided fractionation using different chromatographic and spectroscopic techniques in the analysis of the Red Sea soft coral Litophyton arboreum led to the isolation of nine compounds; sarcophytol M (1), alismol (2), 24-methylcholesta-5,24(28)-diene-3β-ol (3), 10-O-methyl alismoxide
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Bioassay-guided fractionation using different chromatographic and spectroscopic techniques in the analysis of the Red Sea soft coral Litophyton arboreum led to the isolation of nine compounds; sarcophytol M (1), alismol (2), 24-methylcholesta-5,24(28)-diene-3β-ol (3), 10-O-methyl alismoxide (4), alismoxide (5), (S)-chimyl alcohol (6), 7β-acetoxy-24-methylcholesta-5-24(28)-diene-3,19-diol (7), erythro-N-dodecanoyl-docosasphinga-(4E,8E)-dienine (8), and 24-methylcholesta-5,24 (28)-diene-3β,7β,19-triol (9). Some of the isolated compounds demonstrated potent cytotoxic- and/or cytostatic activity against HeLa and U937 cancer cell lines and inhibitory activity against HIV-1 protease (PR). Compound 7 was strongly cytotoxic against HeLa cells (CC50 4.3 ± 0.75 µM), with selectivity index of SI 8.1, which was confirmed by real time cell electronic sensing (RT-CES). Compounds 2, 7, and 8 showed strong inhibitory activity against HIV-1 PR at IC50s of 7.20 ± 0.7, 4.85 ± 0.18, and 4.80 ± 0.92 µM respectively. In silico docking of most compounds presented comparable scores to that of acetyl pepstatin, a known HIV-1 PR inhibitor. Interestingly, compound 8 showed potent HIV-1 PR inhibitory activity in the absence of cytotoxicity against the cell lines used. In addition, compounds 2 and 5 demonstrated cytostatic action in HeLa cells, revealing potential use in virostatic cocktails. Taken together, data presented here suggest Litophyton arboreum to contain promising compounds for further investigation against the diseases mentioned. Full article
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Open AccessArticle Oxygenated Ylangene-Derived Sesquiterpenoids from the Soft Coral Lemnalia philippinensis
Mar. Drugs 2013, 11(10), 3735-3741; doi:10.3390/md11103735
Received: 27 August 2013 / Revised: 11 September 2013 / Accepted: 24 September 2013 / Published: 30 September 2013
Cited by 4 | PDF Full-text (500 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Chemical examination of a Taiwanese soft coral Lemnalia philippinensis led to the isolation of three oxygenated ylangene-derived sesquiterpenoids 13, including two new metabolites, philippinlins A and B (1 and 2). The structures of these compounds were elucidated on
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Chemical examination of a Taiwanese soft coral Lemnalia philippinensis led to the isolation of three oxygenated ylangene-derived sesquiterpenoids 13, including two new metabolites, philippinlins A and B (1 and 2). The structures of these compounds were elucidated on the basis of detailed spectroscopic data. Compound 1 was shown to exhibit cytotoxicity against HepG2, MDA-MB231 and A549 cancer cell lines. Full article

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