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Mar. Drugs, Volume 13, Issue 1 (January 2015), Pages 1-696

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Open AccessArticle Squid Pen Chitin Chitooligomers as Food Colorants Absorbers
Mar. Drugs 2015, 13(1), 681-696; https://doi.org/10.3390/md13010681
Received: 28 August 2014 / Accepted: 9 January 2015 / Published: 20 January 2015
Cited by 5 | PDF Full-text (544 KB) | HTML Full-text | XML Full-text
Abstract
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
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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) Printed Edition available
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Open AccessArticle Marine Structure Derived Calcium Phosphate–Polymer Biocomposites for Local Antibiotic Delivery
Mar. Drugs 2015, 13(1), 666-680; https://doi.org/10.3390/md13010666
Received: 13 November 2014 / Accepted: 12 January 2015 / Published: 20 January 2015
Cited by 16 | PDF Full-text (1103 KB) | HTML Full-text | XML Full-text
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
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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
Mar. Drugs 2015, 13(1), 655-665; https://doi.org/10.3390/md13010655
Received: 4 November 2014 / Revised: 10 December 2014 / Accepted: 9 January 2015 / Published: 19 January 2015
Cited by 4 | PDF Full-text (460 KB) | HTML Full-text | XML Full-text
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 111 were evaluated
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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 111 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
Mar. Drugs 2015, 13(1), 618-654; https://doi.org/10.3390/md13010618
Received: 11 November 2014 / Accepted: 1 January 2015 / Published: 16 January 2015
Cited by 42 | PDF Full-text (1268 KB) | HTML Full-text | XML Full-text
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
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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
Mar. Drugs 2015, 13(1), 597-617; https://doi.org/10.3390/md13010597
Received: 8 August 2014 / Accepted: 1 January 2015 / Published: 16 January 2015
Cited by 6 | PDF Full-text (1473 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Sea cucumbers produce numerous compounds with a wide range of chemical structural diversity. Among these, saponins are the most diverse and include sulfated, non-sulfated, acetylated and methylated congeners with different aglycone and sugar moieties. In this study, MALDI and ESI tandem mass spectrometry,
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Sea cucumbers produce numerous compounds with a wide range of chemical structural diversity. Among these, saponins are the most diverse and include sulfated, non-sulfated, acetylated and methylated congeners with different aglycone and sugar moieties. In this study, MALDI and ESI tandem mass spectrometry, in the positive ion mode, were used to elucidate the structure of new saponins extracted from the viscera of H. lessoni. Fragmentation of the aglycone provided structural information on the presence of the acetyl group. The presence of the O-acetyl group was confirmed by observing the mass transition of 60 u corresponding to the loss of a molecule of acetic acid. Ion fingerprints from the glycosidic cleavage provided information on the mass of the aglycone (core), and the sequence and type of monosaccharides that constitute the sugar moiety. The tandem mass spectra of the saponin precursor ions [M + Na]+ provided a wealth of detailed structural information on the glycosidic bond cleavages. As a result, and in conjunction with existing literature, we characterized the structure of five new acetylated saponins, Lessoniosides A–E, along with two non-acetylated saponins Lessoniosides F and G at m/z 1477.7, which are promising candidates for future drug development. The presented strategy allows a rapid, reliable and complete analysis of native saponins. Full article
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Open AccessArticle Biosynthesis of Akaeolide and Lorneic Acids and Annotation of Type I Polyketide Synthase Gene Clusters in the Genome of Streptomyces sp. NPS554
Mar. Drugs 2015, 13(1), 581-596; https://doi.org/10.3390/md13010581
Received: 3 December 2014 / Accepted: 9 January 2015 / Published: 16 January 2015
Cited by 4 | PDF Full-text (968 KB) | HTML Full-text | XML Full-text | Supplementary Files
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
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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)
Mar. Drugs 2015, 13(1), 558-580; https://doi.org/10.3390/md13010558
Received: 11 November 2014 / Accepted: 4 January 2015 / Published: 16 January 2015
Cited by 15 | PDF Full-text (747 KB) | HTML Full-text | XML Full-text
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,
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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
Mar. Drugs 2015, 13(1), 543-557; https://doi.org/10.3390/md13010543
Received: 16 November 2014 / Accepted: 7 January 2015 / Published: 16 January 2015
Cited by 14 | PDF Full-text (1815 KB) | HTML Full-text | XML Full-text | Supplementary Files
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
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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 p21WAF1/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
Mar. Drugs 2015, 13(1), 529-542; https://doi.org/10.3390/md13010529
Received: 12 November 2014 / Accepted: 7 January 2015 / Published: 16 January 2015
Cited by 18 | PDF Full-text (1285 KB) | HTML Full-text | XML Full-text
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
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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
Mar. Drugs 2015, 13(1), 509-528; https://doi.org/10.3390/md13010509
Received: 30 June 2014 / Accepted: 21 November 2014 / Published: 16 January 2015
Cited by 30 | PDF Full-text (1012 KB) | HTML Full-text | XML Full-text
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
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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
Mar. Drugs 2015, 13(1), 493-508; https://doi.org/10.3390/md13010493
Received: 12 November 2014 / Accepted: 4 January 2015 / Published: 16 January 2015
Cited by 10 | PDF Full-text (1484 KB) | HTML Full-text | XML Full-text
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,
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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
Mar. Drugs 2015, 13(1), 460-492; https://doi.org/10.3390/md13010460
Received: 14 November 2014 / Accepted: 4 January 2015 / Published: 16 January 2015
Cited by 25 | PDF Full-text (983 KB) | HTML Full-text | XML Full-text
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
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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
Mar. Drugs 2015, 13(1), 444-459; https://doi.org/10.3390/md13010444
Received: 3 December 2014 / Accepted: 4 January 2015 / Published: 16 January 2015
Cited by 26 | PDF Full-text (877 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The study of the secondary metabolites contained in the organic extract of Caribbean sponge Smenospongia aurea led to the isolation of smenothiazole A (3) and B (4), hybrid peptide/polyketide compounds. Assays performed using four solid tumor cell lines 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
Mar. Drugs 2015, 13(1), 431-443; https://doi.org/10.3390/md13010431
Received: 9 May 2014 / Accepted: 26 November 2014 / Published: 16 January 2015
Cited by 8 | PDF Full-text (1174 KB) | HTML Full-text | XML Full-text
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
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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
Mar. Drugs 2015, 13(1), 389-430; https://doi.org/10.3390/md13010389
Received: 28 August 2014 / Accepted: 17 December 2014 / Published: 16 January 2015
Cited by 20 | PDF Full-text (1690 KB) | HTML Full-text | XML Full-text
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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