| 1. |
- Al Shemaili, Jasem, et al.
(författare)
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Pharmacokinetics in Mouse and Comparative Effects of Frondosides in Pancreatic Cancer
- 2016
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Ingår i: Marine Drugs. - : MDPI AG. - 1660-3397. ; 14:6
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Tidskriftsartikel (refereegranskat)abstract
- The frondosides are triterpenoid glycosides from the Atlantic sea cucumber Cucumaria frondosa. Frondoside A inhibits growth, invasion, metastases and angiogenesis and induces apoptosis in diverse cancer types, including pancreatic cancer. We compared the growth inhibitory effects of three frondosides and their aglycone and related this to the pharmocokinetics and route of administration. Frondoside A potently inhibited growth of pancreatic cancer cells with an EC50 of similar to 1 mu M. Frondoside B was less potent (EC50 similar to 2.5 mu M). Frondoside C and the aglycone had no effect. At 100 mu g/kg, frondoside A administered to CD2F1 mice as an i.v. bolus, the Cp-max was 129 nM, Cl-tb was 6.35 mL/min/m(2), and half-life was 510 min. With i.p. administration the Cp-max was 18.3 nM, Cl-tb was 127 mL/min/m(2) and half-life was 840 min. Oral dosing was ineffective. Frondoside A (100 mu g/kg/day i.p.) markedly inhibited growth cancer xenografts in nude mice. The same dose delivered by oral gavage had no effect. No evidence of acute toxicity was seen with frondoside A. Frondoside A is more potent inhibitor of cancer growth than other frondosides. The glycoside component is essential for bioactivity. Frondoside A is only effective when administered systemically. Based on the current and previous studies, frondoside A appears safe and may be valuable in the treatment of cancer.
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| 2. |
- Andersen, Toril, et al.
(författare)
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Chitosan-Based Nanomedicine to Fight Genital Candida Infections : Chitosomes
- 2017
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Ingår i: Marine Drugs. - : MDPI. - 1660-3397. ; 15:3
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Tidskriftsartikel (refereegranskat)abstract
- Vaginal infections are associated with high recurrence, which is often due to a lack of efficient treatment of complex vaginal infections comprised of several types of pathogens, especially fungi and bacteria. Chitosan, a mucoadhesive polymer with known antifungal effect, could offer a great improvement in vaginal therapy; the chitosan-based nanosystem could both provide antifungal effects and simultaneously deliver antibacterial drugs. We prepared chitosan-containing liposomes, chitosomes, where chitosan is both embedded in liposomes and surface-available as a coating layer. For antimicrobial activity, we entrapped metronidazole as a model drug. To prove that mucoadhesivness alone is not sufficient for successful delivery, we used Carbopol-containing liposomes as a control. All vesicles were characterized for their size, zeta potential, entrapment efficiency, and in vitro drug release. Chitosan-containing liposomes were able to assure the prolonged release of metronidazole. Their antifungal activity was evaluated in a C. albicans model; chitosan-containing liposomes exhibited a potent ability to inhibit the growth of C. albicans. The presence of chitosan was crucial for the system's antifungal activity. The antifungal efficacy of chitosomes combined with antibacterial potential of the entrapped metronidazole could offer improved efficacy in the treatment of mixed/complex vaginal infections.
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| 3. |
- Andersen, Toril, et al.
(författare)
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Chitosan in Mucoadhesive Drug Delivery : Focus on Local Vaginal Therapy
- 2015
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Ingår i: Marine Drugs. - : MDPI. - 1660-3397. ; 13:1, s. 222-236
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Tidskriftsartikel (refereegranskat)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 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.
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| 4. |
- Andreo-Vidal, Andres, et al.
(författare)
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The Pseudoalteromonas luteoviolacea L-amino Acid Oxidase with Antimicrobial Activity Is a Flavoenzyme
- 2018
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Ingår i: Marine Drugs. - : MDPI. - 1660-3397. ; 16:12
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Tidskriftsartikel (refereegranskat)abstract
- The marine environment is a rich source of antimicrobial compounds with promising pharmaceutical and biotechnological applications. The Pseudoalteromonas genus harbors one of the highest proportions of bacterial species producing antimicrobial molecules. For decades, the presence of proteins with L-amino acid oxidase (LAAO) and antimicrobial activity in Pseudoalteromonas luteoviolacea has been known. Here, we present for the first time the identification, cloning, characterization and phylogenetic analysis of Pl-LAAO, the enzyme responsible for both LAAO and antimicrobial activity in P. luteoviolacea strain CPMOR-2. Pl-LAAO is a flavoprotein of a broad substrate range, in which the hydrogen peroxide generated in the LAAO reaction is responsible for the antimicrobial activity. So far, no protein with a sequence similarity to Pl-LAAO has been cloned or characterized, with this being the first report on a flavin adenine dinucleotide (FAD)-containing LAAO with antimicrobial activity from a marine microorganism. Our results revealed that 20.4% of the sequenced Pseudoalteromonas strains (specifically, 66.6% of P. luteoviolacea strains) contain Pl-laao similar genes, which constitutes a well-defined phylogenetic group. In summary, this work provides insights into the biological significance of antimicrobial LAAOs in the Pseudoalteromonas genus and shows an effective approach for the detection of novel LAAOs, whose study may be useful for biotechnological applications.
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| 5. |
- Baur, Philipp, et al.
(författare)
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Possible Functional Roles of Patellamides in the Ascidian-Prochloron Symbiosis
- 2022
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Ingår i: Marine Drugs. - : MDPI AG. - 1660-3397. ; 20:2
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Tidskriftsartikel (refereegranskat)abstract
- Patellamides are highly bioactive compounds found along with other cyanobactins in the symbiosis between didemnid ascidians and the enigmatic cyanobacterium Prochloron. The biosynthetic pathway of patellamide synthesis is well understood, the relevant operons have been identified in the Prochloron genome and genes involved in patellamide synthesis are among the most highly transcribed cyanobacterial genes in hospite. However, a more detailed study of the in vivo dynamics of patellamides and their function in the ascidian-Prochloron symbiosis is complicated by the fact that Prochloron remains uncultivated despite numerous attempts since its discovery in 1975. A major challenge is to account for the highly dynamic microenvironmental conditions experienced by Prochloron in hospite, where light-dark cycles drive rapid shifts between hyperoxia and anoxia as well as pH variations from pH ~6 to ~10. Recently, work on patellamide analogues has pointed out a range of different catalytic functions of patellamide that could prove essential for the ascidian-Prochloron symbiosis and could be modulated by the strong microenvironmental dynamics. Here, we review fundamental properties of patellamides and their occurrence and dynamics in vitro and in vivo. We discuss possible functions of patellamides in the ascidian-Prochloron symbiosis and identify important knowledge gaps and needs for further experimental studies.
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| 6. |
- Berntzon, Lotta, et al.
(författare)
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BMAA Inhibits Nitrogen Fixation in the Cyanobacterium Nostoc sp PCC 7120
- 2013
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Ingår i: Marine Drugs. - : MDPI AG. - 1660-3397. ; 11:8, s. 3091-3108
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Tidskriftsartikel (refereegranskat)abstract
- Cyanobacteria produce a range of secondary metabolites, one being the neurotoxic non-protein amino acid beta-N-methylamino-L-alanine (BMAA), proposed to be a causative agent of human neurodegeneration. As for most cyanotoxins, the function of BMAA in cyanobacteria is unknown. Here, we examined the effects of BMAA on the physiology of the filamentous nitrogen-fixing cyanobacterium Nostoc sp. PCC 7120. Our data show that exogenously applied BMAA rapidly inhibits nitrogenase activity (acetylene reduction assay), even at micromolar concentrations, and that the inhibition was considerably more severe than that induced by combined nitrogen sources and most other amino acids. BMAA also caused growth arrest and massive cellular glycogen accumulation, as observed by electron microscopy. With nitrogen fixation being a process highly sensitive to oxygen species we propose that the BMAA effects found here may be related to the production of reactive oxygen species, as reported for other organisms.
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| 7. |
- Calabro, K., et al.
(författare)
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Poecillastrosides, Steroidal Saponins from the Mediterranean Deep-Sea Sponge Poecillastra compressa (Bowerbank, 1866)
- 2017
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Ingår i: Marine Drugs. - : MDPI AG. - 1660-3397. ; 15:7
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Tidskriftsartikel (refereegranskat)abstract
- The first chemical investigation of the Mediterranean deep-sea sponge Poecillastra compressa (Bowerbank, 1866) led to the identification of seven new steroidal saponins named poecillastrosides A-G (1-7). All saponins feature an oxidized methyl at C-18 into a primary alcohol or a carboxylic acid. While poecillastrosides A-D (1-4) all contain an exo double bond at C-24 of the side-chain and two osidic residues connected at O-2', poecillastrosides E-G (5-7) are characterized by a cyclopropane on the side-chain and a connection at O-3' between both sugar units. The chemical structures were elucidated through extensive spectroscopic analysis (High-Resolution Mass Spectrometry (HRESIMS), 1D and 2D NMR) and the absolute configurations of the sugar residues were assigned after acidic hydrolysis and cysteine derivatization followed by LC-HRMS analyses. Poecillastrosides D and E, bearing a carboxylic acid at C-18, were shown to exhibit antifungal activity against Aspergillus fumigatus.
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| 8. |
- Cárdenas, Paco, 1976-, et al.
(författare)
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Good Practices in Sponge Natural Product Studies : Revising Vouchers with Isomalabaricane Triterpenes
- 2022
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Ingår i: Marine Drugs. - : MDPI. - 1660-3397. ; 20:3
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Tidskriftsartikel (refereegranskat)abstract
- Species misidentification in the field of natural products is an acknowledged problem. These errors are especially widespread in sponge studies, albeit rarely assessed and documented. As a case study, we aim to revisit reports of isomalabaricane triterpenes, isolated from four demosponge genera: Jaspis, Geodia, Stelletta and Rhabdastrella. From a total of 44 articles (1981-2022), 27 unique vouchers were listed, 21 of which were accessed and re-examined here: 11 (52.4%) of these were misidentified. Overall, 65.9% of the studies published an incorrect species name: previously identified Jaspis and Stelletta species were all in fact Rhabdastrella globostellata. We conclude that isomalabaricane triterpenes were isolated from only two Rhabdastrella species and possibly one Geodia species. In addition to shedding a new light on the distribution of isomalabaricane triterpenes, this study is an opportunity to highlight the crucial importance of vouchers in natural product studies. Doing so, we discuss the impact of species misidentification and poor accessibility of vouchers in the field of sponge natural products. We advocate for stricter voucher guidelines in natural product journals and propose a common protocol of good practice, in the hope of reducing misidentifications in sponge studies, ensure reproducibility of studies, and facilitate follow-up work on the original material.
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| 9. |
- Carrasco Del Amor, Ana Maria, et al.
(författare)
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Application of Bioactive Thermal Proteome Profiling to Decipher the Mechanism of Action of the Lipid Lowering 13(2)-Hydroxy-pheophytin Isolated from a Marine Cyanobacteria
- 2019
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Ingår i: Marine Drugs. - : MDPI. - 1660-3397. ; 17:6
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Tidskriftsartikel (refereegranskat)abstract
- The acceleration of the process of understanding the pharmacological application of new marine bioactive compounds requires identifying the compound protein targets leading the molecular mechanisms in a living cell. The thermal proteome profiling (TPP) methodology does not fulfill the requirements for its application to any bioactive compound lacking chemical and functional characterization. Here, we present a modified method that we called bTPP for bioactive thermal proteome profiling that guarantees target specificity from a soluble subproteome. We showed that the precipitation of the microsomal fraction before the thermal shift assay is crucial to accurately calculate the melting points of the protein targets. As a probe of concept, the protein targets of 13(2)-hydroxy-pheophytin, a compound previously isolated from a marine cyanobacteria for its lipid reducing activity, were analyzed on the hepatic cell line HepG2. Our improved method identified 9 protein targets out of 2500 proteins, including 3 targets (isocitrate dehydrogenase, aldehyde dehydrogenase, phosphoserine aminotransferase) that could be related to obesity and diabetes, as they are involved in the regulation of insulin sensitivity and energy metabolism. This study demonstrated that the bTPP method can accelerate the field of biodiscovery, revealing protein targets involved in mechanisms of action (MOA) connected with future applications of bioactive compounds.
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| 10. |
- Castejon, Natalia, et al.
(författare)
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Valorization of the Red Algae Gelidium sesquipedale by Extracting a Broad Spectrum of Minor Compounds Using Green Approaches
- 2021
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Ingår i: Marine Drugs. - : MDPI. - 1660-3397. ; 19:10
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Tidskriftsartikel (refereegranskat)abstract
- Until now, the red algae Gelidium sesquipedale has been primarily exploited for agar production, leaving an undervalued biomass. In this work, the use of eco-friendly approaches employing ultrasound-assisted extraction (UAE) and green solvents was investigated to valorize the algal minor compounds. The green methods used herein showed an attractive alternative to efficiently extract a broad spectrum of bioactive compounds in short extraction times (15 to 30 min vs. 8 h of the conventional method). Using the best UAE conditions, red seaweed extracts were characterized in terms of total phenolics (189.3 & PLUSMN; 11.7 mg GAE/100 g dw), flavonoids (310.7 & PLUSMN; 9.7 mg QE/100 g dw), mycosporine-like amino acids (MAAs) (sigma MAAs = 1271 mg/100 g dw), and phycobiliproteins (72.4 & PLUSMN; 0.5 mg/100 g dw). Additionally, produced algal extracts exhibited interesting antioxidant and anti-enzymatic activities for potential applications in medical and/or cosmetic products. Thus, this study provides the basis to reach a superior valorization of algal biomass by using alternative methods to extract biologically active compounds following eco-friendly approaches. Moreover, the strategies developed not only open new possibilities for the commercial use of Gelidium sesquipedale, but also for the valorization of different algae species since the techniques established can be easily adapted.
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