Marine Drugs

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Open AccessArticle

Squid Pen Chitin Chitooligomers as Food Colorants Absorbers

by Tzu-Wen Liang, Chih-Ting Huang, Nguyen Anh Dzung and San-Lang Wang

Mar. Drugs 2015, 13(1), 681-696; https://doi.org/10.3390/md13010681 - 20 Jan 2015

Cited by 19 | Viewed by 7262

One of the most promising applications of chitosanase is the conversion of chitinous biowaste into bioactive chitooligomers (COS). TKU033 chitosanase was induced from squid pen powder (SPP)-containing Bacillus cereus TKU033 medium and purified by ammonium sulfate precipitation and column chromatography. The enzyme was [...] Read more.

One of the most promising applications of chitosanase is the conversion of chitinous biowaste into bioactive chitooligomers (COS). TKU033 chitosanase was induced from squid pen powder (SPP)-containing Bacillus cereus TKU033 medium and purified by ammonium sulfate precipitation and column chromatography. The enzyme was relatively more thermostable in the presence of the substrate and had an activity of 93% at 50 °C in a pH 5 buffer solution for 60 min. Furthermore, the enzyme used for the COS preparation was also studied. The enzyme products revealed various mixtures of COS that with different degrees of polymerization (DP), ranging from three to nine. In the culture medium, the fermented SPP was recovered, and it displayed a better adsorption rate (up to 96%) for the disperse dyes than the water-soluble food colorants, Allura Red AC (R40) and Tartrazne (Y4). Fourier transform-infrared spectroscopic (FT-IR) analysis proved that the adsorption of the dyes onto fermented SPP was a physical adsorption. Results also showed that fermented SPP was a favorable adsorber and could be employed as low-cost alternative for dye removal in wastewater treatment. Full article

(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan)

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Open AccessArticle

Marine Structure Derived Calcium Phosphate–Polymer Biocomposites for Local Antibiotic Delivery

by Innocent J. Macha, Sophie Cazalbou, Besim Ben-Nissan, Kate L. Harvey and Bruce Milthorpe

Mar. Drugs 2015, 13(1), 666-680; https://doi.org/10.3390/md13010666 - 20 Jan 2015

Cited by 48 | Viewed by 6451

Abstract

Hydrothermally converted coralline hydroxyapatite (HAp) particles loaded with medically active substances were used to develop polylactic acid (PLA) thin film composites for slow drug delivery systems. The effects of HAp particles within PLA matrix on the gentamicin (GM) release and release kinetics were [...] Read more.

Hydrothermally converted coralline hydroxyapatite (HAp) particles loaded with medically active substances were used to develop polylactic acid (PLA) thin film composites for slow drug delivery systems. The effects of HAp particles within PLA matrix on the gentamicin (GM) release and release kinetics were studied. The gentamicin release kinetics seemed to follow Power law Korsmeyer Peppas model with mainly diffusional process with a number of different drug transport mechanisms. Statistical analysis shows very significant difference on the release of gentamicin between GM containing PLA (PLAGM) and GM containing HAp microspheres within PLA matrix (PLAHApGM) devices, which PLAHApGM displays lower release rates. The use of HAp particles improved drug stabilization and higher drug encapsulation efficiency of the carrier. HAp is also the source of Ca²⁺ for the regeneration and repair of diseased bone tissue. The release profiles, exhibited a steady state release rate with significant antimicrobial activity against Staphylococcus aureus (S. aureus) (SH1000) even at high concentration of bacteria. The devices also indicated significant ability to control the growth of bacterial even after four weeks of drug release. Clinical release profiles can be easily tuned from drug-HAp physicochemical interactions and degradation kinetics of polymer matrix. The developed systems could be applied to prevent microbial adhesion to medical implant surfaces and to treat infections mainly caused by S. aureus in surgery. Full article

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Open AccessArticle

Design, Synthesis and Evaluation of New Marine Alkaloid-Derived Pentacyclic Structures with Anti-Tumoral Potency

by Sebastien Boucle, Celine Melin, Marc Clastre and Jerome Guillard

Mar. Drugs 2015, 13(1), 655-665; https://doi.org/10.3390/md13010655 - 19 Jan 2015

Cited by 9 | Viewed by 5830

Abstract

This work describes the synthesis and biological evaluation of a new heterocyclic hybrid derived from the ellipticine and the marine alkaloid makaluvamine A. Pyridoquinoxalinedione 12 was obtained in seven steps with 6.5% overall yield. 12 and its intermediates 1–11 were evaluated [...] Read more.

This work describes the synthesis and biological evaluation of a new heterocyclic hybrid derived from the ellipticine and the marine alkaloid makaluvamine A. Pyridoquinoxalinedione 12 was obtained in seven steps with 6.5% overall yield. 12 and its intermediates 1–11 were evaluated for their in vitro cytotoxic activity against different cancer cell lines and tested for their inhibitory activity against the human DNA topoisomerase II. The analysis by electrophoresis shows that the pentacycle 12 inhibits the topoisomerase II like doxorubicine at 100 µM. Compound 9 was found to have an interesting profile, having a cytotoxicity of 15, 15, 15 and 10 μM against Caco-2, HCT-116, Pc-3 and NCI cell lines respectively, without any noticeable toxicity against human fibroblast. Full article

(This article belongs to the Special Issue Synthesis around Marine Natural Products)

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Open AccessReview

Marine Peptides and Their Anti-Infective Activities

by Hee Kyoung Kang, Chang Ho Seo and Yoonkyung Park

Mar. Drugs 2015, 13(1), 618-654; https://doi.org/10.3390/md13010618 - 16 Jan 2015

Cited by 124 | Viewed by 12786

Abstract

Marine bioresources are a valuable source of bioactive compounds with industrial and nutraceutical potential. Numerous clinical trials evaluating novel chemotherapeutic agents derived from marine sources have revealed novel mechanisms of action. Recently, marine-derived bioactive peptides have attracted attention owing to their numerous beneficial [...] Read more.

Marine bioresources are a valuable source of bioactive compounds with industrial and nutraceutical potential. Numerous clinical trials evaluating novel chemotherapeutic agents derived from marine sources have revealed novel mechanisms of action. Recently, marine-derived bioactive peptides have attracted attention owing to their numerous beneficial effects. Moreover, several studies have reported that marine peptides exhibit various anti-infective activities, such as antimicrobial, antifungal, antimalarial, antiprotozoal, anti-tuberculosis, and antiviral activities. In the last several decades, studies of marine plants, animals, and microbes have revealed tremendous number of structurally diverse and bioactive secondary metabolites. However, the treatments available for many infectious diseases caused by bacteria, fungi, and viruses are limited. Thus, the identification of novel antimicrobial peptides should be continued, and all possible strategies should be explored. In this review, we will present the structures and anti-infective activity of peptides isolated from marine sources (sponges, algae, bacteria, fungi and fish) from 2006 to the present. Full article

(This article belongs to the Special Issue Marine Anti-infective Agents)

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Open AccessArticle

Structure Elucidation of New Acetylated Saponins, Lessoniosides A, B, C, D, and E, and Non-Acetylated Saponins, Lessoniosides F and G, from the Viscera of the Sea Cucumber Holothuria lessoni

by Yadollah Bahrami and Christopher M. M. Franco

Mar. Drugs 2015, 13(1), 597-617; https://doi.org/10.3390/md13010597 - 16 Jan 2015

Cited by 27 | Viewed by 8550

Abstract

Sea cucumbers produce numerous compounds with a wide range of chemical structural diversity. Among these, saponins are the most diverse and include sulfated, non-sulfated, acetylated and methylated congeners with different aglycone and sugar moieties. In this study, MALDI and ESI tandem mass spectrometry, [...] Read more.

Sea cucumbers produce numerous compounds with a wide range of chemical structural diversity. Among these, saponins are the most diverse and include sulfated, non-sulfated, acetylated and methylated congeners with different aglycone and sugar moieties. In this study, MALDI and ESI tandem mass spectrometry, in the positive ion mode, were used to elucidate the structure of new saponins extracted from the viscera of H. lessoni. Fragmentation of the aglycone provided structural information on the presence of the acetyl group. The presence of the O-acetyl group was confirmed by observing the mass transition of 60 u corresponding to the loss of a molecule of acetic acid. Ion fingerprints from the glycosidic cleavage provided information on the mass of the aglycone (core), and the sequence and type of monosaccharides that constitute the sugar moiety. The tandem mass spectra of the saponin precursor ions [M + Na]⁺ provided a wealth of detailed structural information on the glycosidic bond cleavages. As a result, and in conjunction with existing literature, we characterized the structure of five new acetylated saponins, Lessoniosides A–E, along with two non-acetylated saponins Lessoniosides F and G at m/z 1477.7, which are promising candidates for future drug development. The presented strategy allows a rapid, reliable and complete analysis of native saponins. Full article

(This article belongs to the Special Issue Marine Bioactive Natural Product Studies—A Southern Hemisphere Perspective)

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Open AccessArticle

Biosynthesis of Akaeolide and Lorneic Acids and Annotation of Type I Polyketide Synthase Gene Clusters in the Genome of Streptomyces sp. NPS554

by Tao Zhou, Hisayuki Komaki, Natsuko Ichikawa, Akira Hosoyama, Seizo Sato and Yasuhiro Igarashi

Mar. Drugs 2015, 13(1), 581-596; https://doi.org/10.3390/md13010581 - 16 Jan 2015

Cited by 16 | Viewed by 8270

Abstract

The incorporation pattern of biosynthetic precursors into two structurally unique polyketides, akaeolide and lorneic acid A, was elucidated by feeding experiments with ¹³C-labeled precursors. In addition, the draft genome sequence of the producer, Streptomyces sp. NPS554, was performed and the biosynthetic gene [...] Read more.

The incorporation pattern of biosynthetic precursors into two structurally unique polyketides, akaeolide and lorneic acid A, was elucidated by feeding experiments with ¹³C-labeled precursors. In addition, the draft genome sequence of the producer, Streptomyces sp. NPS554, was performed and the biosynthetic gene clusters for these polyketides were identified. The putative gene clusters contain all the polyketide synthase (PKS) domains necessary for assembly of the carbon skeletons. Combined with the ¹³C-labeling results, gene function prediction enabled us to propose biosynthetic pathways involving unusual carbon-carbon bond formation reactions. Genome analysis also indicated the presence of at least ten orphan type I PKS gene clusters that might be responsible for the production of new polyketides. Full article

(This article belongs to the Special Issue Bioactive Compounds from Marine Microbes)

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Open AccessArticle

Enzyme-Assisted Extraction of Bioactive Material from Chondrus crispus and Codium fragile and Its Effect on Herpes simplex Virus (HSV-1)

by Garima Kulshreshtha, Anne-Sophie Burlot, Christel Marty, Alan Critchley, Jeff Hafting, Gilles Bedoux, Nathalie Bourgougnon and Balakrishnan Prithiviraj

Mar. Drugs 2015, 13(1), 558-580; https://doi.org/10.3390/md13010558 - 16 Jan 2015

Cited by 65 | Viewed by 10827

Abstract

Codium fragile and Chondrus crispus are, respectively, green and red seaweeds which are abundant along the North Atlantic coasts. We investigated the chemical composition and antiviral activity of enzymatic extracts of C. fragile (CF) and C. crispus (CC). On a dry weight basis, [...] Read more.

Codium fragile and Chondrus crispus are, respectively, green and red seaweeds which are abundant along the North Atlantic coasts. We investigated the chemical composition and antiviral activity of enzymatic extracts of C. fragile (CF) and C. crispus (CC). On a dry weight basis, CF consisted of 11% protein, 31% neutral sugars, 0.8% sulfate, 0.6% uronic acids, and 49% ash, while CC contained 27% protein, 28% neutral sugars, 17% sulfate, 1.8% uronic acids, and 25% ash. Enzyme-assisted hydrolysis improved the extraction efficiency of bioactive materials. Commercial proteases and carbohydrases significantly improved (p ≤ 0.001) biomass yield (40%–70% dry matter) as compared to aqueous extraction (20%–25% dry matter). Moreover, enzymatic hydrolysis enhanced the recovery of protein, neutral sugars, uronic acids, and sulfates. The enzymatic hydrolysates exhibited significant activity against Herpes simplex virus (HSV-1) with EC₅₀ of 77.6–126.8 μg/mL for CC and 36.5–41.3 μg/mL for CF, at a multiplicity of infection (MOI) of 0.001 ID₅₀/cells without cytotoxity (1–200 μg/mL). The extracts obtained from proteases (P1) and carbohydrases (C3) were also effective at higher virus MOI of 0.01 ID₅₀/cells without cytotoxity. Taken together, these results indicate the potential application of enzymatic hydrolysates of C. fragile and C. crispus in functional food and antiviral drug discovery. Full article

(This article belongs to the Special Issue Marine Functional Food)

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Open AccessArticle

Activation of p53 with Ilimaquinone and Ethylsmenoquinone, Marine Sponge Metabolites, Induces Apoptosis and Autophagy in Colon Cancer Cells

by Hyun-Young Lee, Kyu Jin Chung, In Hyun Hwang, Jungsuk Gwak, Seoyoung Park, Bong Gun Ju, Eunju Yun, Dong-Eun Kim, Young-Hwa Chung, MinKyun Na, Gyu-Yong Song and Sangtaek Oh

Mar. Drugs 2015, 13(1), 543-557; https://doi.org/10.3390/md13010543 - 16 Jan 2015

Cited by 42 | Viewed by 7724

Abstract

The tumor suppressor, p53, plays an essential role in the cellular response to stress through regulating the expression of genes involved in cell cycle arrest, apoptosis and autophagy. Here, we used a cell-based reporter system for the detection of p53 response transcription to [...] Read more.

The tumor suppressor, p53, plays an essential role in the cellular response to stress through regulating the expression of genes involved in cell cycle arrest, apoptosis and autophagy. Here, we used a cell-based reporter system for the detection of p53 response transcription to identify the marine sponge metabolites, ilimaquinone and ethylsmenoquinone, as activators of the p53 pathway. We demonstrated that ilimaquinone and ethylsmenoquinone efficiently stabilize the p53 protein through promotion of p53 phosphorylation at Ser15 in both HCT116 and RKO colon cancer cells. Moreover, both compounds upregulate the expression of p21^WAF1^/CIP1, a p53-dependent gene, and suppress proliferation of colon cancer cells. In addition, ilimaquinone and ethylsmenoquinone induced G₂/M cell cycle arrest and increased caspase-3 cleavage and the population of cells that positively stained with Annexin V-FITC, both of which are typical biochemical markers of apoptosis. Furthermore, autophagy was elicited by both compounds, as indicated by microtubule-associated protein 1 light chain 3 (LC3) puncta formations and LC3-II turnover in HCT116 cells. Our findings suggest that ilimaquinone and ethylsmenoquinone exert their anti-cancer activity by activation of the p53 pathway and may have significant potential as chemo-preventive and therapeutic agents for human colon cancer. Full article

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Open AccessArticle

Development of Highly Selective Kv1.3-Blocking Peptides Based on the Sea Anemone Peptide ShK

by Michael W. Pennington, Shih Chieh Chang, Satendra Chauhan, Redwan Huq, Rajeev B. Tajhya, Sandeep Chhabra, Raymond S. Norton and Christine Beeton

Mar. Drugs 2015, 13(1), 529-542; https://doi.org/10.3390/md13010529 - 16 Jan 2015

Cited by 53 | Viewed by 9048

Abstract

ShK, from the sea anemone Stichodactyla helianthus, is a 35-residue disulfide-rich peptide that blocks the voltage-gated potassium channel Kv1.3 at ca. 10 pM and the related channel Kv1.1 at ca. 16 pM. We developed an analog of this peptide, ShK-186, which is [...] Read more.

ShK, from the sea anemone Stichodactyla helianthus, is a 35-residue disulfide-rich peptide that blocks the voltage-gated potassium channel Kv1.3 at ca. 10 pM and the related channel Kv1.1 at ca. 16 pM. We developed an analog of this peptide, ShK-186, which is currently in Phase 1b-2a clinical trials for the treatment of autoimmune diseases such as multiple sclerosis and rheumatoid arthritis. While ShK-186 displays a >100-fold improvement in selectivity for Kv1.3 over Kv1.1 compared with ShK, there is considerable interest in developing peptides with an even greater selectivity ratio. In this report, we describe several variants of ShK that incorporate p-phophono-phenylalanine at the N-terminus coupled with internal substitutions at Gln16 and Met21. In addition, we also explored the combinatorial effects of these internal substitutions with an alanine extension at the C-terminus. Their selectivity was determined by patch-clamp electrophysiology on Kv1.3 and Kv1.1 channels stably expressed in mouse fibroblasts. The peptides with an alanine extension blocked Kv1.3 at low pM concentrations and exhibited up to 2250-fold selectivity for Kv1.3 over Kv1.1. Analogs that incorporates p-phosphono-phenylalanine at the N-terminus blocked Kv1.3 with IC₅₀s in the low pM range and did not affect Kv1.1 at concentrations up to 100 nM, displaying a selectivity enhancement of >10,000-fold for Kv1.3 over Kv1.1. Other potentially important Kv channels such as Kv1.4 and Kv1.6 were only partially blocked at 100 nM concentrations of each of the ShK analogs. Full article

(This article belongs to the Special Issue Synthesis around Marine Natural Products)

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Open AccessArticle

Profiling of the Molecular Weight and Structural Isomer Abundance of Macroalgae-Derived Phlorotannins

by Natalie Heffernan, Nigel P. Brunton, Richard J. FitzGerald and Thomas J. Smyth

Mar. Drugs 2015, 13(1), 509-528; https://doi.org/10.3390/md13010509 - 16 Jan 2015

Cited by 130 | Viewed by 11118

Abstract

Phlorotannins are a group of complex polymers of phloroglucinol (1,3,5-trihydroxybenzene) unique to macroalgae. These phenolic compounds are integral structural components of the cell wall in brown algae, but also play many secondary ecological roles such as protection from UV radiation and defense against [...] Read more.

Phlorotannins are a group of complex polymers of phloroglucinol (1,3,5-trihydroxybenzene) unique to macroalgae. These phenolic compounds are integral structural components of the cell wall in brown algae, but also play many secondary ecological roles such as protection from UV radiation and defense against grazing. This study employed Ultra Performance Liquid Chromatography (UPLC) with tandem mass spectrometry to investigate isomeric complexity and observed differences in phlorotannins derived from macroalgae harvested off the Irish coast (Fucus serratus, Fucus vesiculosus, Himanthalia elongata and Cystoseira nodicaulis). Antioxidant activity and total phenolic content assays were used as an index for producing phlorotannin fractions, enriched using molecular weight cut-off dialysis with subsequent flash chromatography to profile phlorotannin isomers in these macroalgae. These fractions were profiled using UPLC-MS with multiple reaction monitoring (MRM) and the level of isomerization for specific molecular weight phlorotannins between 3 and 16 monomers were determined. The majority of the low molecular weight (LMW) phlorotannins were found to have a molecular weight range equivalent to 4–12 monomers of phloroglucinol. The level of isomerization within the individual macroalgal species differed, resulting in substantially different numbers of phlorotannin isomers for particular molecular weights. F. vesiculosus had the highest number of isomers of 61 at one specific molecular mass, corresponding to 12 phloroglucinol units (PGUs). These results highlight the complex nature of these extracts and emphasize the challenges involved in structural elucidation of these compounds. Full article

(This article belongs to the Special Issue Metabolomics - Applications in Marine Natural Products Chemistry)

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Open AccessArticle

Identification of a 4-Deoxy-l-erythro-5-hexoseulose Uronic Acid Reductase, FlRed, in an Alginolytic Bacterium Flavobacterium sp. Strain UMI-01

by Akira Inoue, Ryuji Nishiyama, Shogo Mochizuki and Takao Ojima

Mar. Drugs 2015, 13(1), 493-508; https://doi.org/10.3390/md13010493 - 16 Jan 2015

Cited by 22 | Viewed by 7169

Abstract

In alginate-assimilating bacteria, alginate is depolymerized to unsaturated monosaccharide by the actions of endolytic and exolytic alginate lyases (EC 4.2.2.3 and EC 4.2.2.11). The monosaccharide is non-enzymatically converted to 4-deoxy-l-ery thro-5-hexoseulose uronic acid (DEH), then reduced to 2-keto-3-deoxy-d-gluconate (KDG) by a specific reductase, [...] Read more.

In alginate-assimilating bacteria, alginate is depolymerized to unsaturated monosaccharide by the actions of endolytic and exolytic alginate lyases (EC 4.2.2.3 and EC 4.2.2.11). The monosaccharide is non-enzymatically converted to 4-deoxy-l-ery thro-5-hexoseulose uronic acid (DEH), then reduced to 2-keto-3-deoxy-d-gluconate (KDG) by a specific reductase, and metabolized through the Entner–Doudoroff pathway. Recently, the NADPH-dependent reductase A1-R that belongs to short-chain dehydrogenases/reductases (SDR) superfamily was identified as the DEH-reductase in Sphingomonas sp. A1. We have subsequently noticed that an SDR-like enzyme gene, flred, occurred in the genome of an alginolytic bacterium Flavobacterium sp. strain UMI-01. In the present study, we report on the deduced amino-acid sequence of flred and DEH-reducing activity of recombinant FlRed. The deduced amino-acid sequence of flred comprised 254 residues and showed 34% amino-acid identities to that of A1-R from Sphingomonas sp. A1 and 80%–88% to those of SDR-like enzymes from several alginolytic bacteria. Common sequence motifs of SDR-superfamily enzymes, e.g., the catalytic tetrad Asn-Lys-Tyr-Ser and the cofactor-binding sequence Thr-Gly-x-x-x-Gly-x-Gly in Rossmann fold, were completely conserved in FlRed. On the other hand, an Arg residue that determined the NADPH-specificity of Sphingomonas A1-R was replaced by Glu in FlRed. Thus, we investigated cofactor-preference of FlRed using a recombinant enzyme. As a result, the recombinant FlRed (recFlRed) was found to show high specificity to NADH. recFlRed exhibited practically no activity toward variety of aldehyde, ketone, keto ester, keto acid and aldose substrates except for DEH. On the basis of these results, we conclude that FlRed is the NADH-dependent DEH-specific SDR of Flavobacterium sp. strain UMI-01. Full article

(This article belongs to the Special Issue Green Chemistry Approach to Marine Products)

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Open AccessArticle

Synthesis and Antiproliferative Activity of Thiazolyl-bis-pyrrolo[2,3-b]pyridines and Indolyl-thiazolyl-pyrrolo[2,3-c]pyridines, Nortopsentin Analogues

by Anna Carbone, Barbara Parrino, Gloria Di Vita, Alessandro Attanzio, Virginia Spanò, Alessandra Montalbano, Paola Barraja, Luisa Tesoriere, Maria Antonia Livrea, Patrizia Diana and Girolamo Cirrincione

Mar. Drugs 2015, 13(1), 460-492; https://doi.org/10.3390/md13010460 - 16 Jan 2015

Cited by 53 | Viewed by 7382

Abstract

Two new series of nortopsentin analogues, in which the imidazole ring of the natural product was replaced by thiazole and indole units were both substituted by 7-azaindole moieties or one indole unit was replaced by a 6-azaindole portion, were efficiently synthesized. Compounds belonging [...] Read more.

Two new series of nortopsentin analogues, in which the imidazole ring of the natural product was replaced by thiazole and indole units were both substituted by 7-azaindole moieties or one indole unit was replaced by a 6-azaindole portion, were efficiently synthesized. Compounds belonging to both series inhibited the growth of HCT-116 colorectal cancer cells at low micromolar concentrations, whereas they did not affect the viability of normal-like intestinal cells. A compound of the former series induced apoptosis, evident as externalization of plasma membrane phosphatidylserine (PS), and changes of mitochondrial trans-membrane potential, while blocking the cell cycle in G2/M phase. In contrast, a derivative of the latter series elicited distinct responses in accordance with the dose. Thus, low concentrations (GI₃₀) induced morphological changes characteristic of autophagic death with massive formation of cytoplasmic acid vacuoles without apparent loss of nuclear material, and with arrest of cell cycle at the G1 phase, whereas higher concentrations (GI₇₀) induced apoptosis with arrest of cell cycle at the G1 phase. Full article

(This article belongs to the Special Issue Synthesis around Marine Natural Products)

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Open AccessArticle

Isolation and Assessment of the in Vitro Anti-Tumor Activity of Smenothiazole A and B, Chlorinated Thiazole-Containing Peptide/Polyketides from the Caribbean Sponge, Smenospongia aurea

by Germana Esposito, Roberta Teta, Roberta Miceli, Luca S. Ceccarelli, Gerardo Della Sala, Rosa Camerlingo, Elena Irollo, Alfonso Mangoni, Giuseppe Pirozzi and Valeria Costantino

Mar. Drugs 2015, 13(1), 444-459; https://doi.org/10.3390/md13010444 - 16 Jan 2015

Cited by 51 | Viewed by 8650

Abstract

The study of the secondary metabolites contained in the organic extract of Caribbean sponge Smenospongia aurea led to the isolation of smenothiazole A (3) and B (4), hybrid peptide/polyketide compounds. Assays performed using four solid tumor cell lines showed [...] Read more.

The study of the secondary metabolites contained in the organic extract of Caribbean sponge Smenospongia aurea led to the isolation of smenothiazole A (3) and B (4), hybrid peptide/polyketide compounds. Assays performed using four solid tumor cell lines showed that smenothiazoles exert a potent cytotoxic activity at nanomolar levels, with selectivity over ovarian cancer cells and a pro-apoptotic mechanism. Full article

(This article belongs to the Special Issue Marine Secondary Metabolites)

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Open AccessArticle

Ophiobolin O Isolated from Aspergillus ustus Induces G1 Arrest of MCF-7 Cells through Interaction with AKT/GSK3β/Cyclin D1 Signaling

by Cuiting Lv, Wenxing Qin, Tonghan Zhu, Shanjian Wei, Kui Hong, Weiming Zhu, Ruohua Chen and Caiguo Huang

Mar. Drugs 2015, 13(1), 431-443; https://doi.org/10.3390/md13010431 - 16 Jan 2015

Cited by 25 | Viewed by 7417

Abstract

Ophiobolin O is a member of ophiobolin family, which has been proved to be a potent anti-tumor drug candidate for human breast cancer. However, the anti-tumor effect and the mechanism of ophiobolin O remain unclear. In this study, we further verified ophiobolin O-induced [...] Read more.

Ophiobolin O is a member of ophiobolin family, which has been proved to be a potent anti-tumor drug candidate for human breast cancer. However, the anti-tumor effect and the mechanism of ophiobolin O remain unclear. In this study, we further verified ophiobolin O-induced G1 phase arrest in human breast cancer MCF-7 cells, and found that ophiobolin O reduced the phosphorylation level of AKT and GSK3β, and induced down-regulation of cyclin D1. The inverse docking (INVDOCK) analysis indicated that ophiobolin O could bind to GSK3β, and GSK3β knockdown abolished cyclin D1 degradation and G1 phase arrest. Pre-treatment with phosphatase inhibitor sodium or thovanadate halted dephosphorylation of AKT and GSK3β, and blocked ophiobolin O-induced G1 phase arrest. These data suggest that ophiobolin O may induce G1 arrest in MCF-7 cells through interaction with AKT/GSK3β/cyclin D1 signaling. In vivo, ophiobolin O suppressed tumor growth and showed little toxicity in mouse xenograft models. Overall, these findings provide theoretical basis for the therapeutic use of ophiobolin O. Full article

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Open AccessReview

Magnetotactic Bacteria as Potential Sources of Bioproducts

by Ana Carolina V. Araujo, Fernanda Abreu, Karen Tavares Silva, Dennis A. Bazylinski and Ulysses Lins

Mar. Drugs 2015, 13(1), 389-430; https://doi.org/10.3390/md13010389 - 16 Jan 2015

Cited by 64 | Viewed by 13266

Abstract

Magnetotactic bacteria (MTB) produce intracellular organelles called magnetosomes which are magnetic nanoparticles composed of magnetite (Fe₃O₄) or greigite (Fe₃S₄) enveloped by a lipid bilayer. The synthesis of a magnetosome is through a genetically controlled process [...] Read more.

Magnetotactic bacteria (MTB) produce intracellular organelles called magnetosomes which are magnetic nanoparticles composed of magnetite (Fe₃O₄) or greigite (Fe₃S₄) enveloped by a lipid bilayer. The synthesis of a magnetosome is through a genetically controlled process in which the bacterium has control over the composition, direction of crystal growth, and the size and shape of the mineral crystal. As a result of this control, magnetosomes have narrow and uniform size ranges, relatively specific magnetic and crystalline properties, and an enveloping biological membrane. These features are not observed in magnetic particles produced abiotically and thus magnetosomes are of great interest in biotechnology. Most currently described MTB have been isolated from saline or brackish environments and the availability of their genomes has contributed to a better understanding and culturing of these fastidious microorganisms. Moreover, genome sequences have allowed researchers to study genes related to magnetosome production for the synthesis of magnetic particles for use in future commercial and medical applications. Here, we review the current information on the biology of MTB and apply, for the first time, a genome mining strategy on these microorganisms to search for secondary metabolite synthesis genes. More specifically, we discovered that the genome of the cultured MTB Magnetovibrio blakemorei, among other MTB, contains several metabolic pathways for the synthesis of secondary metabolites and other compounds, thereby raising the possibility of the co-production of new bioactive molecules along with magnetosomes by this species. Full article

(This article belongs to the Special Issue Marine Biomaterials)

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Open AccessArticle

Combination of Trabectedin and Gemcitabine for Advanced Soft Tissue Sarcomas: Results of a Phase I Dose Escalating Trial of the German Interdisciplinary Sarcoma Group (GISG)

by Bernd Kasper, Peter Reichardt, Daniel Pink, Michaela Sommer, Monika Mathew, Geraldine Rauch and Peter Hohenberger

Mar. Drugs 2015, 13(1), 379-388; https://doi.org/10.3390/md13010379 - 13 Jan 2015

Cited by 8 | Viewed by 5977

Abstract

Background: Evaluation of the potential efficacy and safety of combination therapies for advanced soft tissue sarcomas (STS) has increased substantially after approval of trabectedin and pazopanib. Trabectedin's introduction in Europe in 2007 depended mainly on its activity in so-called L-sarcomas (liposarcoma and leiomyosarcoma); [...] Read more.

Background: Evaluation of the potential efficacy and safety of combination therapies for advanced soft tissue sarcomas (STS) has increased substantially after approval of trabectedin and pazopanib. Trabectedin's introduction in Europe in 2007 depended mainly on its activity in so-called L-sarcomas (liposarcoma and leiomyosarcoma); combination of trabectedin with other chemotherapies used in STS seems of particular interest. Methods: We initiated within the German Interdisciplinary Sarcoma Group (GISG) a phase I dose escalating trial evaluating the combination of trabectedin and gemcitabine in patients with advanced and/or metastatic L-sarcomas (GISG-02; ClinicalTrials.gov NCT01426633). Patients were treated with increasing doses of trabectedin and gemcitabine. The primary endpoint was to determine the maximum tolerated dose. Results: Five patients were included in the study. Two patients were treated on dose level 1 comprising trabectedin 0.9 mg/m2 on day 1 and gemcitabine 700 mg/m2 on days 1 + 8, every 3 weeks. Due to dose-limiting toxicity (DLT) in both patients (elevated transaminases and thrombocytopenia), an additional three patients were treated on dose level −1 with trabectedin 0.7 mg/m2 plus gemcitabine 700 mg/m2. Of these three patients, two demonstrated another DLT; therefore, the trial was stopped and none of the dose levels could be recommended for phase II testing. Conclusion: The GISG-02 phase I study was stopped with the conclusion that the combination of gemcitabine and trabectedin is generally not recommended for the treatment of patients with advanced and/or metastatic leiomyosarcoma or liposarcoma. Also, this phase I study strongly supports the necessity for careful evaluation of combination therapies. Full article

(This article belongs to the Collection Marine Compounds and Cancer)

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Open AccessArticle

Asperlones A and B, Dinaphthalenone Derivatives from a Mangrove Endophytic Fungus Aspergillus sp. 16-5C

by Ze'en Xiao, Shao'e Lin, Chunbing Tan, Yongjun Lu, Lei He, Xishan Huang and Zhigang She

Mar. Drugs 2015, 13(1), 366-378; https://doi.org/10.3390/md13010366 - 13 Jan 2015

Cited by 28 | Viewed by 7635

Abstract

Racemic dinaphthalenone derivatives, (±)-asperlone A (1) and (±)-asperlone B (2), and two new azaphilones, 6′-hydroxy-(R)-mitorubrinic acid (3) and purpurquinone D (4), along with four known compounds, (−)-mitorubrinic acid (5), (−)-mitorubrin ( [...] Read more.

Racemic dinaphthalenone derivatives, (±)-asperlone A (1) and (±)-asperlone B (2), and two new azaphilones, 6′-hydroxy-(R)-mitorubrinic acid (3) and purpurquinone D (4), along with four known compounds, (−)-mitorubrinic acid (5), (−)-mitorubrin (6), purpurquinone A (7) and orsellinic acid (8), were isolated from the cultures of Aspergillus sp. 16-5C. The structures were elucidated using comprehensive spectroscopic methods, including 1D and 2D NMR spectra and the structures of 1 further confirmed by single-crystal X-ray diffraction analysis, while the absolute configuration of 3 and 4 were determined by comparing their optical rotation and CD with those of the literature, respectively. Compounds 1, 2 and 6 exhibited potent inhibitory effects against Mycobacterium tuberculosis protein tyrosine phosphatase B (MptpB) with IC₅₀ values of 4.24 ± 0.41, 4.32 ± 0.60 and 3.99 ± 0.34 μM, respectively. Full article

(This article belongs to the Special Issue Bioactive Compounds from Marine Microbes)

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Open AccessArticle

Preparative Separation of Sulfur-Containing Diketopiperazines from Marine Fungus Cladosporium sp. Using High-Speed Counter-Current Chromatography in Stepwise Elution Mode

by Binbin Gu, Yanying Zhang, Lijian Ding, Shan He, Bin Wu, Junde Dong, Peng Zhu, Juanjuan Chen, Jinrong Zhang and Xiaojun Yan

Mar. Drugs 2015, 13(1), 354-365; https://doi.org/10.3390/md13010354 - 09 Jan 2015

Cited by 28 | Viewed by 7090

Abstract

High-speed counter-current chromatography (HSCCC) was successively applied to the separation of three sulfur-containing diketopiperazines (DKPs) (including two new compounds cladosporin A (1) and cladosporin B (3), and a known compound haematocin (2)) from a marine fungus Cladosporium [...] Read more.

High-speed counter-current chromatography (HSCCC) was successively applied to the separation of three sulfur-containing diketopiperazines (DKPs) (including two new compounds cladosporin A (1) and cladosporin B (3), and a known compound haematocin (2)) from a marine fungus Cladosporium sp. The two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water at (1:1:1:1, v/v) and (2:1:2:1, v/v), in stepwise elution mode, was used for HSCCC. The preparative HSCCC separation was performed on 300 mg of crude sample yielding 26.7 mg of compound 3 at a purity of over 95%, 53.6 mg of a mixture of compounds 1 and 2, which was further separated by preparative-HPLC yielding 14.3 mg of compound 1 and 25.4 mg of compound 2 each at a purity of over 95%. Their structures were established by spectroscopic methods. The sulfur-containing DKPs suppressed the proliferation of hepatocellular carcinoma cell line HepG2. The present work represents the first application of HSCCC in the efficient preparation of marine fungal natural products. Full article

(This article belongs to the Special Issue Marine Natural Products - Advances in Separation, Characterisation and Chemical Profiling Methodologies)

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Open AccessArticle

Preparation of Photocrosslinked Fish Elastin Polypeptide/Microfibrillated Cellulose Composite Gels with Elastic Properties for Biomaterial Applications

by Shinya Yano, Megumi Mori, Naozumi Teramoto, Makoto Iisaka, Natsumi Suzuki, Masanari Noto, Yasuko Kaimoto, Masashi Kakimoto, Michio Yamada, Eri Shiratsuchi, Toshiaki Shimasaki and Mitsuhiro Shibata

Mar. Drugs 2015, 13(1), 338-353; https://doi.org/10.3390/md13010338 - 09 Jan 2015

Cited by 13 | Viewed by 8582

Abstract

Photocrosslinked hydrogels reinforced by microfibrillated cellulose (MFC) were prepared from a methacrylate-functionalized fish elastin polypeptide and MFC dispersed in dimethylsulfoxide (DMSO). First, a water-soluble elastin peptide with a molecular weight of ca. 500 g/mol from the fish bulbus arteriosus was polymerized by N [...] Read more.

Photocrosslinked hydrogels reinforced by microfibrillated cellulose (MFC) were prepared from a methacrylate-functionalized fish elastin polypeptide and MFC dispersed in dimethylsulfoxide (DMSO). First, a water-soluble elastin peptide with a molecular weight of ca. 500 g/mol from the fish bulbus arteriosus was polymerized by N,N′-dicyclohexylcarbodiimide (DCC), a condensation reagent, and then modified with 2-isocyanatoethyl methacrylate (MOI) to yield a photocrosslinkable fish elastin polypeptide. The product was dissolved in DMSO and irradiated with UV light in the presence of a radical photoinitiator. We obtained hydrogels successfully by substitution of DMSO with water. The composite gel with MFC was prepared by UV irradiation of the photocrosslinkable elastin polypeptide mixed with dispersed MFC in DMSO, followed by substitution of DMSO with water. The tensile test of the composite gels revealed that the addition of MFC improved the tensile properties, and the shape of the stress–strain curve of the composite gel became more similar to the typical shape of an elastic material with an increase of MFC content. The rheology measurement showed that the elastic modulus of the composite gel increased with an increase of MFC content. The cell proliferation test on the composite gel showed no toxicity. Full article

(This article belongs to the Special Issue Marine Biomaterials)

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Open AccessReview

Recent Modifications of Chitosan for Adsorption Applications: A Critical and Systematic Review

by George Z. Kyzas and Dimitrios N. Bikiaris

Mar. Drugs 2015, 13(1), 312-337; https://doi.org/10.3390/md13010312 - 09 Jan 2015

Cited by 372 | Viewed by 17932

Abstract

Chitosan is considered to be one of the most promising and applicable materials in adsorption applications. The existence of amino and hydroxyl groups in its molecules contributes to many possible adsorption interactions between chitosan and pollutants (dyes, metals, ions, phenols, pharmaceuticals/drugs, pesticides, herbicides, [...] Read more.

Chitosan is considered to be one of the most promising and applicable materials in adsorption applications. The existence of amino and hydroxyl groups in its molecules contributes to many possible adsorption interactions between chitosan and pollutants (dyes, metals, ions, phenols, pharmaceuticals/drugs, pesticides, herbicides, etc.). These functional groups can help in establishing positions for modification. Based on the learning from previously published works in literature, researchers have achieved a modification of chitosan with a number of different functional groups. This work summarizes the published works of the last three years (2012–2014) regarding the modification reactions of chitosans (grafting, cross-linking, etc.) and their application to adsorption of different environmental pollutants (in liquid-phase). Full article

(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan)

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Open AccessArticle

Araguspongine C Induces Autophagic Death in Breast Cancer Cells through Suppression of c-Met and HER2 Receptor Tyrosine Kinase Signaling

by Mohamed R. Akl, Nehad M. Ayoub, Hassan Y. Ebrahim, Mohamed M. Mohyeldin, Khaled Y. Orabi, Ahmed I. Foudah and Khalid A. El Sayed

Mar. Drugs 2015, 13(1), 288-311; https://doi.org/10.3390/md13010288 - 08 Jan 2015

Cited by 31 | Viewed by 8701

Abstract

Receptor tyrosine kinases are key regulators of cellular growth and proliferation. Dysregulations of receptor tyrosine kinases in cancer cells may promote tumorigenesis by multiple mechanisms including enhanced cell survival and inhibition of cell death. Araguspongines represent a group of macrocyclic oxaquinolizidine alkaloids isolated [...] Read more.

Receptor tyrosine kinases are key regulators of cellular growth and proliferation. Dysregulations of receptor tyrosine kinases in cancer cells may promote tumorigenesis by multiple mechanisms including enhanced cell survival and inhibition of cell death. Araguspongines represent a group of macrocyclic oxaquinolizidine alkaloids isolated from the marine sponge Xestospongia species. This study evaluated the anticancer activity of the known oxaquinolizidine alkaloids araguspongines A, C, K and L, and xestospongin B against breast cancer cells. Araguspongine C inhibited the proliferation of multiple breast cancer cell lines in vitro in a dose-dependent manner. Interestingly, araguspongine C-induced autophagic cell death in HER2-overexpressing BT-474 breast cancer cells was characterized by vacuole formation and upregulation of autophagy markers including LC3A/B, Atg3, Atg7, and Atg16L. Araguspongine C-induced autophagy was associated with suppression of c-Met and HER2 receptor tyrosine kinase activation. Further in-silico docking studies and cell-free Z-LYTE assays indicated the potential of direct interaction between araguspongine C and the receptor tyrosine kinases c-Met and HER2 at their kinase domains. Remarkably, araguspongine C treatment resulted in the suppression of PI3K/Akt/mTOR signaling cascade in breast cancer cells undergoing autophagy. Induction of autophagic death in BT-474 cells was also associated with decreased levels of inositol 1,4,5-trisphosphate receptor upon treatment with effective concentration of araguspongine C. In conclusion, results of this study are the first to reveal the potential of araguspongine C as an inhibitor to receptor tyrosine kinases resulting in the induction of autophagic cell death in breast cancer cells. Full article

(This article belongs to the Collection Marine Compounds and Cancer)

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Open AccessArticle

Penicibrocazines A–E, Five New Sulfide Diketopiperazines from the Marine-Derived Endophytic Fungus Penicillium brocae

by Ling-Hong Meng, Peng Zhang, Xiao-Ming Li and Bin-Gui Wang

Mar. Drugs 2015, 13(1), 276-287; https://doi.org/10.3390/md13010276 - 07 Jan 2015

Cited by 63 | Viewed by 6668

Abstract

Five new sulfide diketopiperazine derivatives, namely, penicibrocazines A–E (1–5), along with a known congener (6), were isolated and identified from the culture extract of Penicillium brocae MA-231, an endophytic fungus obtained from the fresh tissue of the [...] Read more.

Five new sulfide diketopiperazine derivatives, namely, penicibrocazines A–E (1–5), along with a known congener (6), were isolated and identified from the culture extract of Penicillium brocae MA-231, an endophytic fungus obtained from the fresh tissue of the marine mangrove plant Avicennia marina. The structures of these compounds were elucidated by detailed interpretation of NMR and mass spectroscopic data and the structures of compounds 1 and 3 were confirmed by single-crystal X-ray diffraction analysis. All these compounds were examined for cytotoxic and antimicrobial activities. Compounds 2–6 exhibited antimicrobial activity against some of the tested strains with MIC values ranging from 0.25 to 64 μg/mL. Full article

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Open AccessEditorial

Acknowledgement to Reviewers of Marine Drugs in 2014

by Marine Drugs Editorial Office

Mar. Drugs 2015, 13(1), 267-275; https://doi.org/10.3390/md13010267 - 07 Jan 2015

Viewed by 4079

Abstract

The editors of Marine Drugs would like to express their sincere gratitude to the following reviewers for assessing manuscripts in 2014:[...] Full article

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Open AccessArticle

LC-MS-Based Metabolomics Study of Marine Bacterial Secondary Metabolite and Antibiotic Production in Salinispora arenicola

by Utpal Bose, Amitha K. Hewavitharana, Yi Kai Ng, Paul Nicholas Shaw, John A. Fuerst and Mark P. Hodson

Mar. Drugs 2015, 13(1), 249-266; https://doi.org/10.3390/md13010249 - 07 Jan 2015

Cited by 44 | Viewed by 11092

Abstract

An LC-MS-based metabolomics approach was used to characterise the variation in secondary metabolite production due to changes in the salt content of the growth media as well as across different growth periods (incubation times). We used metabolomics as a tool to investigate the [...] Read more.

An LC-MS-based metabolomics approach was used to characterise the variation in secondary metabolite production due to changes in the salt content of the growth media as well as across different growth periods (incubation times). We used metabolomics as a tool to investigate the production of rifamycins (antibiotics) and other secondary metabolites in the obligate marine actinobacterial species Salinispora arenicola, isolated from Great Barrier Reef (GBR) sponges, at two defined salt concentrations and over three different incubation periods. The results indicated that a 14 day incubation period is optimal for the maximum production of rifamycin B, whereas rifamycin S and W achieve their maximum concentration at 29 days. A “chemical profile” link between the days of incubation and the salt concentration of the growth medium was shown to exist and reliably represents a critical point for selection of growth medium and harvest time. Full article

(This article belongs to the Special Issue Metabolomics - Applications in Marine Natural Products Chemistry)

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Open AccessArticle

New Meroterpenoids from the Endophytic Fungus Aspergillus flavipes AIL8 Derived from the Mangrove Plant Acanthus ilicifolius

by Zhi-Qiang Bai, Xiuping Lin, Junfeng Wang, Xuefeng Zhou, Juan Liu, Bin Yang, Xianwen Yang, Shengrong Liao, Lishu Wang and Yonghong Liu

Mar. Drugs 2015, 13(1), 237-248; https://doi.org/10.3390/md13010237 - 07 Jan 2015

Cited by 41 | Viewed by 7862

Abstract

Four new meroterpenoids (2–5), along with three known analogues (1, 6, and 7) were isolated from mangrove plant Acanthus ilicifolius derived endophytic fungus Aspergillus flavipes. The structures of these compounds were elucidated by NMR and [...] Read more.

Four new meroterpenoids (2–5), along with three known analogues (1, 6, and 7) were isolated from mangrove plant Acanthus ilicifolius derived endophytic fungus Aspergillus flavipes. The structures of these compounds were elucidated by NMR and MS analysis, the configurations were assigned by CD data, and the stereochemistry of 1 was confirmed by X-ray crystallography analysis. A possible biogenetic pathway of compounds 1–7 was also proposed. All compounds were evaluated for antibacterial and cytotoxic activities. Full article

(This article belongs to the Special Issue Terpenoids of Marine Origin)

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Open AccessArticle

Chitosan in Mucoadhesive Drug Delivery: Focus on Local Vaginal Therapy

by Toril Andersen, Stefan Bleher, Gøril Eide Flaten, Ingunn Tho, Sofia Mattsson and Nataša Škalko-Basnet

Mar. Drugs 2015, 13(1), 222-236; https://doi.org/10.3390/md13010222 - 07 Jan 2015

Cited by 47 | Viewed by 8919

Abstract

Mucoadhesive drug therapy destined for localized drug treatment is gaining increasing importance in today’s drug development. Chitosan, due to its known biodegradability, bioadhesiveness and excellent safety profile offers means to improve mucosal drug therapy. We have used chitosan as mucoadhesive polymer to develop [...] Read more.

Mucoadhesive drug therapy destined for localized drug treatment is gaining increasing importance in today’s drug development. Chitosan, due to its known biodegradability, bioadhesiveness and excellent safety profile offers means to improve mucosal drug therapy. We have used chitosan as mucoadhesive polymer to develop liposomes able to ensure prolonged residence time at vaginal site. Two types of mucoadhesive liposomes, namely the chitosan-coated liposomes and chitosan-containing liposomes, where chitosan is both embedded and surface-available, were made of soy phosphatidylcholine with entrapped fluorescence markers of two molecular weights, FITC-dextran 4000 and 20,000, respectively. Both liposomal types were characterized for their size distribution, zeta potential, entrapment efficiency and the in vitro release profile, and compared to plain liposomes. The proof of chitosan being both surface-available as well as embedded into the liposomes in the chitosan-containing liposomes was found. The capability of the surface-available chitosan to interact with the model porcine mucin was confirmed for both chitosan-containing and chitosan-coated liposomes implying potential mucoadhesive behavior. Chitosan-containing liposomes were shown to be superior in respect to the simplicity of preparation, FITC-dextran load, mucoadhesiveness and in vitro release and are expected to ensure prolonged residence time on the vaginal mucosa providing localized sustained release of entrapped model substances. Full article

(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan)

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Open AccessArticle

Statistical Research on the Bioactivity of New Marine Natural Products Discovered during the 28 Years from 1985 to 2012

by Yiwen Hu, Jiahui Chen, Guping Hu, Jianchen Yu, Xun Zhu, Yongcheng Lin, Shengping Chen and Jie Yuan

Mar. Drugs 2015, 13(1), 202-221; https://doi.org/10.3390/md13010202 - 07 Jan 2015

Cited by 191 | Viewed by 15753

Abstract

Every year, hundreds of new compounds are discovered from the metabolites of marine organisms. Finding new and useful compounds is one of the crucial drivers for this field of research. Here we describe the statistics of bioactive compounds discovered from marine organisms from [...] Read more.

Every year, hundreds of new compounds are discovered from the metabolites of marine organisms. Finding new and useful compounds is one of the crucial drivers for this field of research. Here we describe the statistics of bioactive compounds discovered from marine organisms from 1985 to 2012. This work is based on our database, which contains information on more than 15,000 chemical substances including 4196 bioactive marine natural products. We performed a comprehensive statistical analysis to understand the characteristics of the novel bioactive compounds and detail temporal trends, chemical structures, species distribution, and research progress. We hope this meta-analysis will provide useful information for research into the bioactivity of marine natural products and drug development. Full article

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Open AccessArticle

Synthesis of Enantiopure Reversed Structured Ether Lipids of the 1-O-Alkyl-sn-2,3-diacylglycerol Type

by Carlos D. Magnusson, Anna V. Gudmundsdottir, Kai-Anders Hansen and Gudmundur G. Haraldsson

Mar. Drugs 2015, 13(1), 173-201; https://doi.org/10.3390/md13010173 - 07 Jan 2015

Cited by 8 | Viewed by 6830

Abstract

This report describes the synthesis of reversed structured 1-O-alkyl-2,3-diacyl-sn-glycerols (DAGEs) possessing a pure saturated even number fatty acid (C6:0–C16:0) at the sn-2 position along with a pure EPA or DHA located at the terminal sn-3 position of [...] Read more.

This report describes the synthesis of reversed structured 1-O-alkyl-2,3-diacyl-sn-glycerols (DAGEs) possessing a pure saturated even number fatty acid (C6:0–C16:0) at the sn-2 position along with a pure EPA or DHA located at the terminal sn-3 position of the glycerol backbone of chimyl, batyl and selachyl alcohols. These adducts were synthesized by a highly efficient two-step chemoenzymatic process involving an immobilized Candida antarctica lipase to introduce pure EPA and DHA activated as oxime esters exclusively to the sn-3 terminal position of enantiopure chimyl, batyl and selachyl alcohols in excellent yields. The saturated fatty acids were subsequently incorporated to the remaining sn-2 position of the resulting 3-monoacylglyceryl ethers (3-MAGEs) using EDAC coupling agent in the presence of DMAP in very high to excellent yields (85%–98%). No losses of enantiomeric composition were observed during these processes. The multiple utilities of the resulting focused library of reversed structured DAGEs are discussed including how such compounds may possibly be utilized within the pharmaceutical area. Full article

(This article belongs to the Special Issue Synthesis around Marine Natural Products)

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Open AccessArticle

Total Synthesis of Gobiusxanthin Stereoisomers and Their Application to Determination of Absolute Configurations of Natural Products: Revision of Reported Absolute Configuration of Epigobiusxanthin

by Yumiko Yamano, Kotaro Ematsu, Hiromasa Kurimoto, Takashi Maoka and Akimori Wada

Mar. Drugs 2015, 13(1), 159-172; https://doi.org/10.3390/md13010159 - 30 Dec 2014

Cited by 1 | Viewed by 5825

Abstract

(3R)-Gobiusxanthin stereoisomers (1a–d) were synthesized by stereoselective Wittig reaction of the (3R)-C₁₅-acetylenic tri-n-butylphosphonium salt 7 with C₂₅-apocarotenal stereoisomers 5a,b and 14a,b bearing four kinds of [...] Read more.

(3R)-Gobiusxanthin stereoisomers (1a–d) were synthesized by stereoselective Wittig reaction of the (3R)-C₁₅-acetylenic tri-n-butylphosphonium salt 7 with C₂₅-apocarotenal stereoisomers 5a,b and 14a,b bearing four kinds of 3,6-dihydroxy-ε-end groups. The validity of the reported stereochemistry of gobiusxanthin was demonstrated by the fact that the reported spectral data of natural gobiusxanthin were in agreement with those of synthetic (3R,3'S,6'R)-gobiusxanthin (1a). On the other hand, the reported CD spectral data of natural epigobiusxanthin, which has been assigned as (3R,3'R,6'R)-isomer (3'-epigobiusxanthin), were identical with those of synthetic (3R,3'S,6'S)-isomer 1d (6'-epigobiusxanthin) rather than those of the corresponding synthetic 3'-epi-isomer 1b. It was found that the stereochemistry at C3-position has little effect on the shape of their CD spectra. Thus, in order to reinforce the validity of the absolute configurations at C3-position of natural specimens, (3S,3'S,6'R)- and (3S,3'S,6'S)-stereoisomers 1e and 1f were also synthesized and a HPLC analytical method for four stereoisomers was established by using a column carrying a chiral stationary phase. The HPLC analysis has proven that the stereochemistry of the natural epigobiusxanthin is 3R,3'S,6'S. Full article

(This article belongs to the Special Issue Marine Natural Products - Advances in Separation, Characterisation and Chemical Profiling Methodologies)

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Open AccessArticle

Does the Use of Chitosan Contribute to Oxalate Kidney Stone Formation?

by Moacir Fernandes Queiroz, Karoline Rachel Teodosio Melo, Diego Araujo Sabry, Guilherme Lanzi Sassaki and Hugo Alexandre Oliveira Rocha

Mar. Drugs 2015, 13(1), 141-158; https://doi.org/10.3390/md13010141 - 29 Dec 2014

Cited by 681 | Viewed by 15659

Abstract

Chitosan is widely used in the biomedical field due its chemical and pharmacological properties. However, intake of chitosan results in renal tissue accumulation of chitosan and promotes an increase in calcium excretion. On the other hand, the effect of chitosan on the formation [...] Read more.

Chitosan is widely used in the biomedical field due its chemical and pharmacological properties. However, intake of chitosan results in renal tissue accumulation of chitosan and promotes an increase in calcium excretion. On the other hand, the effect of chitosan on the formation of calcium oxalate crystals (CaOx) has not been described. In this work, we evaluated the antioxidant capacity of chitosan and its interference in the formation of CaOx crystals in vitro. Here, the chitosan obtained commercially had its identity confirmed by nuclear magnetic resonance and infrared spectroscopy. In several tests, this chitosan showed low or no antioxidant activity. However, it also showed excellent copper-chelating activity. In vitro, chitosan acted as an inducer mainly of monohydrate CaOx crystal formation, which is more prevalent in patients with urolithiasis. We also observed that chitosan modifies the morphology and size of these crystals, as well as changes the surface charge of the crystals, making them even more positive, which can facilitate the interaction of these crystals with renal cells. Chitosan greatly influences the formation of crystals in vitro, and in vivo analyses should be conducted to assess the risk of using chitosan. Full article

(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan)

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