| 1. |
- Ahlberg, Simon, et al.
(author)
-
An information fusion demonstrator for tactical intelligence processing in network-based defense
- 2007
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In: Information Fusion. - : Elsevier BV. - 1566-2535 .- 1872-6305. ; 8:1, s. 84-107
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Journal article (peer-reviewed)abstract
- The Swedish Defence Research Agency (FOI) has developed a concept demonstrator called the Information Fusion Demonstrator 2003 (IFD03) for demonstrating information fusion methodology suitable for a future Network Based Defense (NBD) C4ISR system. The focus of the demonstrator is on real-time tactical intelligence processing at the division level in a ground warfare scenario. The demonstrator integrates novel force aggregation, particle filtering, and sensor allocation methods to create, dynamically update, and maintain components of a tactical situation picture. This is achieved by fusing physically modelled and numerically simulated sensor reports from several different sensor types with realistic a priori information sampled from both a high-resolution terrain model and an enemy organizational and behavioral model. This represents a key step toward the goal of creating in real time a dynamic, high fidelity representation of a moving battalion-sized organization, based on sensor data as well as a priori intelligence and terrain information, employing fusion, tracking, aggregation, and resource allocation methods all built on well-founded theories of uncertainty. The motives behind this project, the fusion methods developed for the system, as well as its scenario model and simulator architecture are described. The main services of the demonstrator are discussed and early experience from using the system is shared.
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| 2. |
- Ahlberg, Simon, et al.
(author)
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The IFD03 information fusion demonstrator
- 2004
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In: Proceedings of the Seventh International Conference on Information Fusion, FUSION 2004. - 917056115X ; , s. 936-943
-
Conference paper (peer-reviewed)abstract
- The paper discusses a recently developed demonstrator system where new ideas in tactical information fusion may be tested and demonstrated. The main services of the demonstrator are discussed, and essential experience from the use and development of the system is shared.
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| 3. |
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| 4. |
- Håkansson, Joakim, 1975, et al.
(author)
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In vitro and in vivo antibacterial properties of peptide AMC-109 impregnated wound dressings and gels
- 2021
-
In: Journal of Antibiotics. - : Springer Science and Business Media LLC. - 0021-8820 .- 1881-1469. ; 74, s. 337-345
-
Journal article (peer-reviewed)abstract
- Synthetic mimics of antimicrobial peptides (AMPs) is a promising class of molecules for a variety of antimicrobial applications. Several hurdles must be passed before effective systemic infection therapies with AMPs can be achieved, but the path to effective topical treatment of skin, nail, and soft tissue infections appears less challenging to navigate. Skin and soft tissue infection is closely coupled to the emergence of antibiotic resistance and represents a major burden to the healthcare system. The present study evaluates the promising synthetic cationic AMP mimic, AMC-109, for treatment of skin infections in vivo. The compound is evaluated both in impregnated cotton wound dressings and in a gel formulation against skin infections caused by Staphylococcus aureus and methicillin resistant S. aureus. Both the ability to prevent colonization and formation of an infection, as well as eradicate an ongoing infection in vivo with a high bacterial load, were evaluated. The present work demonstrates that AMC-109 displays a significantly higher antibacterial activity with up to a seven-log reduction in bacterial loads compared to current clinical standard therapy; Altargo cream (1% retapamulin) and Fucidin cream (2% fusidic acid) in the in vivo wound models. It is thus concluded that AMC-109 represents a promising entry in the development of new and effective remedies for various skin infections.
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| 5. |
- Labriere, C., et al.
(author)
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Development and evaluation of cationic amphiphilic antimicrobial 2,5-diketopiperazines
- 2018
-
In: Journal of Peptide Science. - : Wiley. - 1075-2617 .- 1099-1387. ; 24:7
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Journal article (peer-reviewed)abstract
- Both pathogenic bacteria and fungi are developing resistance to common antimicrobial treatment at an alarming rate. To counteract this development, it is of essence to develop new classes of antimicrobial agents. One such class is antimicrobial peptides, most of which are derived from the innate immune system. In this study, a series of novel 2,5-diketopiperazines were designed, synthesized, and evaluated for their antimicrobial abilities. The compounds were designed to probe the pharmacophore dictated for short linear mimics of antimicrobial cationic peptides, and as such, the compounds contain a range of cationic and hydrophobic functionalities. Several of the prepared compounds displayed high antimicrobial activities toward bacteria and also against human pathogenic fungi. Of particular interest was the high activity toward fungal strains with an inherent increased resistance toward conventional antifungal agents. The most effective compounds displayed inhibition of Candida glabrata and Candida krusei growth at concentrations between 4 and 8 mu g/mL, which is comparable to commercial antifungal agents in use. Structure activity relationship studies revealed a similar dependence on cationic charge and the volume of the hydrophobic bulk as for linear cationic antimicrobial peptides. Finally, the hemolytic activity of selected compounds was evaluated, which revealed a potential to produce active compounds with attenuation of unwanted hemolysis. The findings highlight the potential of cyclic cationic amphiphilic peptidomimetics as a class of promising compounds for the treatment of infections caused by microorganisms with an increased resistance to conventional antimicrobial agents.
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| 6. |
- Olsen, Elisabeth K., et al.
(author)
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Marine AChE inhibitors isolated from Geodia barretti : Natural compounds and their synthetic analogs
- 2016
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In: Organic and biomolecular chemistry. - : Royal Society of Chemistry. - 1477-0520 .- 1477-0539. ; 14:5, s. 1629-1640
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Journal article (peer-reviewed)abstract
- Barettin, 8,9-dihydrobarettin, bromoconicamin and a novel brominated marine indole were isolated from the boreal sponge Geodia barretti collected off the Norwegian coast. The compounds were evaluated as inhibitors of electric eel acetylcholinesterase. Barettin and 8,9-dihydrobarettin displayed significant inhibition of the enzyme, with inhibition constants (Ki) of 29 and 19 μM respectively towards acetylcholinesterase via a reversible noncompetitive mechanism. These activities are comparable to those of several other natural acetylcholinesterase inhibitors of marine origin. Bromoconicamin was less potent against acetylcholinesterase, and the novel compound was inactive. Based on the inhibitory activity, a library of 22 simplified synthetic analogs was designed and prepared to probe the role of the brominated indole, common to all the isolated compounds. From the structure-activity investigation it was shown that the brominated indole motif is not sufficient to generate a high acetylcholinesterase inhibitory activity, even when combined with natural cationic ligands for the acetylcholinesterase active site. The four natural compounds were also analysed for their butyrylcholinesterase inhibitory activity in addition and shown to display comparable activities. The study illustrates how both barettin and 8,9-dihydrobarettin display additional bioactivities which may help to explain their biological role in the producing organism. The findings also provide new insights into the structure-activity relationship of both natural and synthetic acetylcholinesterase inhibitors.
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| 7. |
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| 8. |
- Solstad, Runar Gjerp, et al.
(author)
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Novel antimicrobial peptides EeCentrocins 1, 2 and EeStrongylocin 2 from the Edible sea urchin Echinus esculentus have 6-br-trp post-translational modifications
- 2016
-
In: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 11:3
-
Journal article (peer-reviewed)abstract
- The global problem of microbial resistance to antibiotics has resulted in an urgent need to develop new antimicrobial agents. Natural antimicrobial peptides are considered promising candidates for drug development. Echinoderms, which rely on innate immunity factors in the defence against harmful microorganisms, are sources of novel antimicrobial peptides. This study aimed to isolate and characterise antimicrobial peptides from the Edible sea urchin Echinus esculentus. Using bioassay-guided purification and cDNA cloning, three antimicrobial peptides were characterised from the haemocytes of the sea urchin; two heterodimeric peptides and a cysteine-rich peptide. The peptides were named EeCentrocin 1 and 2 and EeStrongylocin 2, respectively, due to their apparent homology to the published centrocins and strongylocins isolated from the green sea urchin Strongylocentrotus droebachiensis. The two centrocin-like peptides EeCentrocin 1 and 2 are intramolecularly connected via a disulphide bond to form a heterodimeric structure, containing a cationic heavy chain of 30 and 32 amino acids and a light chain of 13 amino acids. Additionally, the light chain of EeCentrocin 2 seems to be N-terminally blocked by a pyroglutamic acid residue. The heavy chains of EeCentrocins 1 and 2 were synthesised and shown to be responsible for the antimicrobial activity of the natural peptides. EeStrongylocin 2 contains 6 cysteines engaged in 3 disulphide bonds. A fourth peptide (Ee4635) was also discovered but not fully characterised. Using mass spectrometric and NMR analyses, EeCentrocins 1 and 2, EeStrongylocin 2 and Ee4635 were all shown to contain post-translationally brominated Trp residues in the 6 position of the indole ring.
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| 9. |
- Vinagre, Pedro, et al.
(author)
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Probing the correlation between corrosion resistance and biofouling of thermally sprayed metallic substrata in the field
- 2022
-
In: Biofouling (Print). - : Taylor and Francis Ltd.. - 0892-7014 .- 1029-2454. ; 38:2, s. 147-161
-
Journal article (peer-reviewed)abstract
- The correlation between inherent corrosion resistance and biofouling was investigated for five different metallic coatings. Steel panels thermally spray-coated with either aluminium, Monel, bronze or different aluminium alloys were tested in controlled salt mist conditions and electrochemical corrosion tests and subsequently employed at sea. The biofouling of the panels was monitored at different depths (5, 10 and 15 m) at periods ranging from 5 to 12 months. The main macrofouling organisms were quantified and analysed using permutational multivariate analysis. The results indicate a significant difference in fouling pressure between depths and the geographic sites used. No statistically significant link between high corrosion resistance and lower biofouling pressure was observed, indicating that the main marine macrofoulers settled equally well on corrosion resistant and corrosion prone metallic surfaces. This work sheds light on biofouling of thermally sprayed metallic substrata and it characterizes and compares biofouling assemblages from different biogeographical regions in Europe.
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| 10. |
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| 11. |
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| 12. |
- Berglin, Mattias, 1970, et al.
(author)
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Flexible and Biocompatible Antifouling Polyurethane Surfaces Incorporating Tethered Antimicrobial Peptides through Click Reactions
- 2024
-
In: Macromolecular Bioscience. - : John Wiley and Sons Inc. - 1616-5187 .- 1616-5195. ; 24:4
-
Journal article (peer-reviewed)abstract
- Efficient, simple antibacterial materials to combat implant-associated infections are much in demand. Herein, the development of polyurethanes, both cross-linked thermoset and flexible and versatile thermoplastic, suitable for “click on demand” attachment of antibacterial compounds enabled via incorporation of an alkyne-containing diol monomer in the polymer backbone, is described. By employing different polyolic polytetrahydrofurans, isocyanates, and chain extenders, a robust and flexible material comparable to commercial thermoplastic polyurethane is prepared. A series of short synthetic antimicrobial peptides are designed, synthesized, and covalently attached in a single coupling step to generate a homogenous coating. The lead material is shown to be biocompatible and does not display any toxicity against either mouse fibroblasts or reconstructed human epidermis according to ISO and OECD guidelines. The repelling performance of the peptide-coated materials is illustrated against colonization and biofilm formation by Staphylococcus aureus and Staphylococcus epidermidis on coated plastic films and finally, on coated commercial central venous catheters employing LIVE/DEAD staining, confocal laser scanning microscopy, and bacterial counts. This study presents the successful development of a versatile and scalable polyurethane with the potential for use in the medical field to reduce the impact of bacterial biofilms.
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| 13. |
- Brooke, Darby G., et al.
(author)
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Antifouling activity of portimine, select semisynthetic analogues, and other microalga-derived spirocyclic imines
- 2018
-
In: Biofouling. - : Informa UK Limited. - 0892-7014 .- 1029-2454. ; 34:8, s. 950-961
-
Journal article (peer-reviewed)abstract
- © 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group. A range of natural products from marine invertebrates, bacteria and fungi have been assessed as leads for nature-inspired antifouling (AF) biocides, but little attention has been paid to microalgal-derived compounds. This study assessed the AF activity of the spirocyclic imine portimine (1), which is produced by the benthic mat-forming dinoflagellate Vulcanodinium rugosum. Portimine displayed potent AF activity in a panel of four macrofouling bioassays (EC 50 0.06–62.5 ng ml −1 ), and this activity was distinct from that of the related compounds gymnodimine-A (2), 13-desmethyl spirolide C (3), and pinnatoxin-F (4). The proposed mechanism of action for portimine is induction of apoptosis, based on the observation that portimine inhibited macrofouling organisms at developmental stages known to involve apoptotic processes. Semisynthetic modification of select portions of the portimine molecule was subsequently undertaken. Observed changes in bioactivity of the resulting semisynthetic analogues of portimine were consistent with portimine’s unprecedented 5-membered imine ring structure playing a central role in its AF activity.
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| 14. |
- Cahill, P. L., et al.
(author)
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Creating New Antifoulants Using the Tools and Tactics of Medicinal Chemistry
- 2024
-
In: Accounts of Chemical Research. - : American Chemical Society. - 0001-4842 .- 1520-4898. ; 57:3, s. 399-
-
Journal article (peer-reviewed)abstract
- Conspectus The unwanted accumulation of marine micro- and macroorganisms such as algae and barnacles on submerged man-made structures and vessel hulls is a major challenge for any marine operation. Known as biofouling, this problem leads to reduced hydrodynamic efficiency, significantly increased fuel usage, microbially induced corrosion, and, if not managed appropriately, eventual loss of both performance and structural integrity. Ship hull biofouling in the international maritime transport network conservatively accounts for 0.6% of global carbon emissions, highlighting the global scale and the importance of this problem. Improved antifouling strategies to limit surface colonization are paramount for essential activities such as shipping, aquaculture, desalination, and the marine renewable energy sector, representing both a multibillion dollar cost and a substantial practical challenge. From an ecological perspective, biofouling is a primary contributor to the global spread of invasive marine species, which has extensive implications for the marine environment. Historically, heavy metal-based toxic biocides have been used to control biofouling. However, their unwanted collateral ecological damage on nontarget species and bioaccumulation has led to recent global bans. With expanding human activities within aquaculture and offshore energy, it is both urgent and apparent that environmentally friendly surface protection remains key for maintaining the function of both moving and stationary marine structures. Biofouling communities are typically a highly complex network of both micro- and macroorganisms, representing a broad section of life from bacteria to macrophytes and animals. Given this diversity, it is unrealistic to expect that a single antifouling “silver bullet” will prevent colonization with the exception of generally toxic biocides. For that reason, modern and future antifouling solutions are anticipated to rely on novel coating technologies and “combination therapies” where mixtures of narrow-spectrum bioactive components are used to provide coverage across fouling species. In contrast to the existing cohort of outdated, toxic antifouling strategies, such as copper- and tributyltin-releasing paints, modern drug discovery techniques are increasingly being employed for the rational design of effective yet safe alternatives. The challenge for a medicinal chemistry approach is to effectively account for the large taxonomic diversity among fouling organisms combined with a lack of well-defined conserved molecular targets within most taxa. The current Account summarizes our work employing the tools of modern medicinal chemistry to discover, modify, and develop optimized and scalable antifouling solutions based on naturally occurring antifouling and repelling compounds from both marine and terrestrial sources. Inspiration for rational design comes from targeted studies on allelopathic natural products, natural repelling peptides, and secondary metabolites from sessile marine organisms with clean exteriors, which has yielded several efficient and promising antifouling leads.
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| 15. |
- Cahill, Patrick, et al.
(author)
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Nature-Inspired Peptide Antifouling Biocide : Coating Compatibility, Field Validation, and Environmental Stability
- 2023
-
In: ACS Applied Bio Materials. - : American Chemical Society. - 2576-6422. ; 6:6, s. 2415-2425
-
Journal article (peer-reviewed)abstract
- This study reports the development of a class of eco-friendly antifouling biocides based on a cyclic dipeptide scaffold, 2,5-diketopiperazine (2,5-DKP). The lead compound cyclo(N-Bip-l-Arg-N-Bip-l-Arg) (1) was synthesized in gram amounts and used to assess the compatibility with an ablation/hydration coating, efficacy against biofouling, and biodegradation. Leaching of 1 from the coating into seawater was assessed via a rotating drum method, revealing relatively stable and predictable leaching rates under dynamic shear stress conditions (36.1 ± 19.7 to 25.2 ± 9.1 ng-1 cm-2 day-1) but low or no leaching under static conditions. The coatings were further analyzed using time-of-flight secondary ion mass spectrometry (ToF-SIMS), with 1 seen to localize at the surface of the coating in a surfactant-like fashion. When coatings were deployed in the ocean, detectable reductions in biofouling development were measured for up to 11 weeks. After this time, biofouling overwhelmed the performance of the coating, consistent with leaching kinetics. Biodegradation of 1 in seawater was assessed using theoretical oxygen demand and analytical quantification. Masking effects were observed at higher concentrations of 1 due to antimicrobial properties, but half-lives were calculated ranging from 13.4 to 16.2 days. The results can rationally inform future development toward commercial antifouling products.
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| 16. |
- Craig, Alexander J., et al.
(author)
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Antimicrobial Peptides Incorporating Halogenated Marine-Derived Amino Acid Substituents
- 2023
-
In: ACS Medicinal Chemistry Letters. - : American Chemical Society (ACS). - 1948-5875 .- 1948-5875. ; 14:6, s. 802-809
-
Journal article (peer-reviewed)abstract
- Small synthetic mimics of cationic antimicrobial peptides represent a promising class of compounds with leads in clinical development for the treatment of persistent microbial infections. The activity and selectivity of these compounds rely on a balance between hydrophobic and cationic components, and here, we explore the activity of 19 linear cationic tripeptides against five different pathogenic bacteria and fungi, including clinical isolates. The compounds incorporated modified hydrophobic amino acids inspired by motifs often found in bioactive marine secondary metabolites in combination with different cationic residues to probe the possibility of generating active compounds with improved safety profiles. Several of the compounds displayed high activity (low mu M concentrations), comparable with the positive controls AMC-109, amoxicillin, and amphotericin B. A higher activity was observed against the fungal strains, and a low in vitro off-target toxicity was observed against erythrocytes and HeLa cells, thereby illustrating effective means for tuning the activity and selectivity of short antimicrobial peptides.
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| 17. |
- Dahlin, Johan, et al.
(author)
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Combining Entity Matching Techniques for Detecting Extremist Behavior on Discussion Boards
- 2012
-
In: Advances in Social Networks Analysis and Mining (ASONAM), 2012. - : IEEE. - 9781467324977 - 9780769547992 ; , s. 850-857
-
Conference paper (peer-reviewed)abstract
- Many extremist groups and terrorists use the Web for various purposes such as exchanging and reinforcing their beliefs, making monitoring and analysis of discussion boards an important task for intelligence analysts in order to detect individuals that might pose a threat towards society. In this work we focus on how to automatically analyze discussion boards in an effective manner. More specifically, we propose a method for fusing several alias (entity) matching techniques, that can be used to identify authors with multiple aliases. This is one part of a larger system, where the aim is to provide the analyst with a list of potential extremist worth investigating further.
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| 18. |
- Greco, I., et al.
(author)
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Correlation between hemolytic activity, cytotoxicity and systemic in vivo toxicity of synthetic antimicrobial peptides
- 2020
-
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
-
Journal article (peer-reviewed)abstract
- The use of non-standard toxicity models is a hurdle in the early development of antimicrobial peptides towards clinical applications. Herein we report an extensive in vitro and in vivo toxicity study of a library of 24 peptide-based antimicrobials with narrow spectrum activity towards veterinary pathogens. The haemolytic activity of the compounds was evaluated against four different species and the relative sensitivity against the compounds was highest for canine erythrocytes, intermediate for rat and human cells and lowest for bovine cells. Selected peptides were additionally evaluated against HeLa, HaCaT and HepG2 cells which showed increased stability towards the peptides. Therapeutic indexes of 50-500 suggest significant cellular selectivity in comparison to bacterial cells. Three peptides were administered to rats in intravenous acute dose toxicity studies up to 2-8 x MIC. None of the injected compounds induced any systemic toxic effects in vivo at the concentrations employed illustrating that the correlation between the different assays is not obvious. This work sheds light on the in vitro and in vivo toxicity of this class of promising compounds and provides insights into the relationship between the different toxicity models often employed in different manners to evaluate the toxicity of novel bioactive compounds in general.
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| 19. |
- Hanssen, Kine Œ, et al.
(author)
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The Bromotyrosine derivative Ianthelline isolated from the arctic marine sponge Stryphnus fortis inhibits marine micro- and macrobiofouling
- 2014
-
In: Marine Biotechnology. - : Springer Science and Business Media LLC. - 1436-2228 .- 1436-2236. ; 16:6, s. 684-694
-
Journal article (peer-reviewed)abstract
- The inhibition of marine biofouling by the bromotyrosine derivative ianthelline, isolated from the Arctic marine sponge Stryphnus fortis, is described. All major stages of the fouling process are investigated. The effect of ianthelline on adhesion and growth of marine bacteria and microalgae is tested to investigate its influence on the initial microfouling process comparing with the known marine antifoulant barettin as a reference. Macrofouling is studied via barnacle (Balanus improvisus) settlement assays and blue mussel (Mytilus edulis) phenoloxidase inhibition. Ianthelline is shown to inhibit both marine micro- and macrofoulers with a pronounced effect on marine bacteria (minimum inhibitory concentration (MIC) values 0.1–10 μg/mL) and barnacle larval settlement (IC50=3.0 μg/mL). Moderate effects are recorded on M. edulis (IC50=45.2 μg/mL) and microalgae, where growth is more affected than surface adhesion. The effect of ianthelline is also investigated against human pathogenic bacteria. Ianthelline displayed low micromolar MIC values against several bacterial strains, both Gram positive and Gram negative, down to 2.5 μg/mL. In summary, the effect of ianthelline on 20 different representative marine antifouling organisms and seven human pathogenic bacterial strains is presented.
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| 20. |
- Herzberg, Moshe, et al.
(author)
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Efficient prevention of marine biofilm formation employing a surface-grafted repellent marine peptide
- 2021
-
In: ACS Applied Bio Materials. - : American Chemical Society. - 2576-6422. ; 4:4, s. 3360-3373
-
Journal article (peer-reviewed)abstract
- Creation of surfaces resistant to the formation of microbial biofilms via biomimicry has been heralded as a promising strategy to protect a range of different materials ranging from boat hulls to medical devices and surgical instruments. In our current study, we describe the successful transfer of a highly effective natural marine biofilm inhibitor to the 2D surface format. A series of cyclic peptides inspired by the natural equinatoxin II protein produced by Beadlet anemone (Actinia equine) have been evaluated for their ability to inhibit the formation of a mixed marine microbial consortium on polyamide reverse osmosis membranes. In solution, the peptides are shown to effectively inhibit settlement and biofilm formation in a nontoxic manner down to 1 nM concentrations. In addition, our study also illustrates how the peptides can be applied to disperse already established biofilms. Attachment of a hydrophobic palmitic acid tail generates a peptide suited for strong noncovalent surface interactions and allows the generation of stable noncovalent coatings. These adsorbed peptides remain attached to the surface at significant shear stress and also remain active, effectively preventing the biofilm formation over 24 h. Finally, the covalent attachment of the peptides to an acrylate surface was also evaluated and the prepared coatings display a remarkable ability to prevent surface colonization at surface loadings of 55 ng/cm2 over 48 h. The ability to retain the nontoxic antibiofilm activity, documented in solution, in the covalent 2D-format is unprecedented, and this natural peptide motif displays high potential in several material application areas.
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| 21. |
- Karlsen, Eskil, et al.
(author)
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Anti-colonization effect of au surfaces with self-assembled molecular monolayers functionalized with antimicrobial peptides on s. Epidermidis
- 2021
-
In: Antibiotics. - : MDPI. - 0066-4774 .- 2079-6382. ; 10:12
-
Journal article (peer-reviewed)abstract
- Medical devices with an effective anti-colonization surface are important tools for com-batting healthcare-associated infections. Here, we investigated the anti-colonization efficacy of antimicrobial peptides covalently attached to a gold model surface. The gold surface was modified by a self-assembled polyethylene glycol monolayer with an acetylene terminus. The peptides were covalently connected to the surface through a copper-catalyzed [3 + 2] azide-acetylene coupling (CuAAC). The anti-colonization efficacy of the surfaces varied as a function of the antimicrobial activity of the peptides, and very effective surfaces could be prepared with a 6 log unit reduction in bacterial colonization. © 2021 by the authors.
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| 22. |
- Labriere, Christophe, et al.
(author)
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Heterocyclic cellular lipid peroxidation inhibitors inspired by the marine antioxidant barettin
- 2019
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In: Bioorganic chemistry (Print). - : Elsevier BV. - 0045-2068. ; 84, s. 106-114
-
Journal article (peer-reviewed)abstract
- The marine environment remains a rich source for the discovery and development of novel bioactive compounds. The present paper describes the design, synthesis and biological evaluation of a library of small molecule heterocyclic mimetics of the marine 2,5-diketopiperazine barettin which is a powerful natural antioxidant. By mainly focusing on the influence from the brominated indole and heterocyclic core of barettin, a library of 19 compounds was prepared. The compounds comprised a heterocyclic core, either a 2,5 diketopiperazine, an imidazolidinedione or a thioxothiazolidinone, which were mainly monosubstituted with ranging bulky substituents. The prepared compounds were screened for activity in a cellular lipid peroxidation assay using HepG2 cells. Several of the synthetic compounds showed antioxidant properties superior to the positive control barettin. Two of the prepared compounds displayed inhibitory activity similar to commercial antioxidants with significant inhibition at low µg/mL concentrations. The toxicity of the compounds was also investigated against MRC-5 lung fibroblasts and none of the included compounds displayed any toxicity at 50 µg/mL.
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| 23. |
- Labriere, Chrostophe, et al.
(author)
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Phidianidine A and synthetic analogues as naturally inspired marine antifoulants
- 2020
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In: Journal of Natural Products. - : American Chemical Society. - 0163-3864 .- 1520-6025. ; 83:11, s. 3413-3423
-
Journal article (peer-reviewed)abstract
- Stationary and slow-moving marine organisms regularly employ a natural product chemical defense to prevent being colonized by marine micro- and macroorganisms. While these natural antifoulants can be structurally diverse, they often display highly conserved chemistries and physicochemical properties, suggesting a natural marine antifouling pharmacophore. In our current report, we investigate the marine natural product phidianidine A, which displays several chemical properties found in highly potent marine antifoulants. Phidianidine A and synthetic analogues were screened against the settlement and metamorphosis of Amphibalanus improvisus cyprids, and several of the compounds displayed inhibitory activities at low micromolar concentrations with IC50 values down to 0.7 μg/mL observed. The settlement study highlights that phidianidine A is a potent natural antifoulant and that the scaffold can be tuned to generate simpler and improved synthetic analogues. The bioactivity is closely linked to the size of the compound and to its basicity. The study also illustrates that active analogues can be prepared in the absence of the natural constrained 1,2,4-oxadiazole ring. A synthetic lead analogue of phidianidine A was incorporated in a coating and included in antifouling field trials, where it was shown that the coating induced potent inhibition of marine bacteria and microalgae settlement.
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| 24. |
- Legrand, Sacha, et al.
(author)
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Preparation, characterization and application of a stationary chromatographic phase from a new (+)-tartaric acid derivative
- 2010
-
In: Tetrahedron Letters. - : Elsevier BV. - 0040-4039 .- 1359-8562. ; 51:17, s. 2258-2261
-
Journal article (peer-reviewed)abstract
- The preparation, characterization and application of a new stationary phase derived from 1,4-cyclohexanedione and diethyl (+)-tartrate are described. A suitable TADDOL for immobilization has been synthesized and grafted to a gamma-mercaptopropylsilylated silica gel. The resulting modified stationary phase has been characterized and its ability to separate enantiomers has been studied. While the free TADDOL in solution was able to resolve a range of enantiomers, the resolving properties were lost on immobilization. Solid state C-13 CPMAS NMR of the new stationary phase was used to explain the lack of stereoselective recognition. (C) 2010 Elsevier Ltd. All rights reserved.
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| 25. |
- Moe, Morten K., et al.
(author)
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The structure of the fire fighting foam surfactant Forafac (R) 1157 and its biological and photolytic transformation products
- 2012
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In: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 89:7, s. 869-875
-
Journal article (peer-reviewed)abstract
- For several decades, perfluorooctane sulfonate (PFOS) has widely been used as a fluorinated surfactant in aqueous film forming foams used as hydrocarbon fuel fire extinguishers. Due to concerns regarding its environmental persistence and toxicological effects, PFOS has recently been replaced by novel fluorinated surfactants such as Forafac (R) 1157, developed by the DuPont company. The major component of Forafac (R) 1157 is a 6:2 fluorotelomer sulfonamide alkylbetaine (6:2 FTAB), and a link between the trade name and the exact chemical structure is presented here to the scientific community for the first time. In the present work, the structure of the 6:2 FTAB was elucidated by H-1, C-13 and F-19 nuclear magnetic resonance Spectroscopy and high-resolution mass spectrometry. Moreover, its major metabolites from blue mussel (Mytilus edulis) and turbot (Scophthalmus maximus) and its photolytic transformation products were identified. Contrary to what has earlier been observed for PFOS, the 6:2 FTAB was extensively metabolized by blue mussel and turbot exposed to Forafac (R) 1157. The major metabolite was a deacetylated betaine species, from which mono- and di-demethylated metabolites also were formed. Another abundant metabolite was the 6:2 fluorotelomer sulfonamide. In another experiment, Forafac (R) 1157 was subjected to UV-light induced photolysis. The experimental conditions aimed to simulate Arctic conditions and the deacetylated species was again the primary transformation product of 6:2 FTAB. A 6:2 fluorotelomer sulfonamide was also formed along with a non-identified transformation product. The environmental presence of most of the metabolites and transformation products was qualitatively demonstrated by analysis of soil samples taken in close proximity to an airport fire training facility.
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| 26. |
- Moodie, Lindon W. K., et al.
(author)
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Design and Biological Evaluation of Antifouling Dihydrostilbene Oxime Hybrids
- 2018
-
In: Marine Biotechnology. - : Springer Science and Business Media LLC. - 1436-2228 .- 1436-2236. ; 20:2, s. 257-267
-
Journal article (peer-reviewed)abstract
- By combining the recently reported repelling natural dihydrostilbene scaffold with an oxime moiety found in many marine antifoulants, a library of nine antifouling hybrid compounds was developed and biologically evaluated. The prepared compounds were shown to display a low antifouling effect against marine bacteria but a high potency against the attachment and growth of microalgae down to MIC values of 0.01 mu g/mL for the most potent hybrid. The mode of action can be characterized as repelling via a reversible non-toxic biostatic mechanism. Barnacle cyprid larval settlement was also inhibited at low mu g/mL concentrations with low levels or no toxicity observed. Several of the prepared compounds performed better than many reported antifouling marine natural products. While several of the prepared compounds are highly active as antifoulants, no apparent synergy is observed by incorporating the oxime functionality into the dihydrostilbene scaffold. This observation is discussed in light of recently reported literature data on related marine natural antifoulants and antifouling hybrids as a potentially general strategy for generation of improved antifoulants.
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| 27. |
- Moodie, Lindon W. K., et al.
(author)
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Natural cholinesterase inhibitors from marine organisms
- 2019
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In: Natural product reports (Print). - : Royal Society of Chemistry (RSC). - 0265-0568 .- 1460-4752. ; 36:8, s. 1053-1092
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Research review (peer-reviewed)abstract
- Inhibition of cholinesterases is a common approach for the management of several disease states. Most notably, cholinesterase inhibitors are used to alleviate the symptoms of neurological disorders like dementia and Alzheimer's disease and treat myasthenia gravis and glaucoma. Historically, most drugs of natural origin have been isolated from terrestrial sources and inhibitors of cholinesterases are no exception. However, the last 50 years have seen a rise in the quantity of marine natural products with close to 25 000 reported in the scientific literature. A number of marine natural products with potent cholinesterase inhibitory properties have also been reported; isolated from a variety of marine sources from algae to ascidians. Representing a diverse range of structural classes, these compounds provide inspirational leads that could aid the development of therapeutics. The current paper aims to, for the first time, comprehensively summarize the literature pertaining to cholinesterase inhibitors derived from marine sources, including the first papers published in 1974 up to 2018. The review does not report bioactive extracts, only isolated compounds, and a specific focus lies on compounds with reported doseresponse data. In vivo and mechanistic data is included for compounds where this is reported. In total 185 marine cholinesterase inhibitors and selected analogs have been identified and reported and some of the compounds display inhibitory activities comparable or superior to cholinesterase inhibitors in clinical use.
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| 28. |
- Moodie, Lindon W. K., et al.
(author)
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Probing the Structure-Activity Relationship of the Natural Antifouling Agent Polygodial against both Micro- and Macrofoulers by Semisynthetic Modification
- 2017
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In: Journal of natural products (Print). - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025. ; 80:2, s. 515-525
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Journal article (peer-reviewed)abstract
- The current study represents the first comprehensive investigation into the general antifouling activities of the natural drimane sesquiterpene polygodial. Previous studies have highlighted a high antifouling effect toward macrofoulers, such as ascidians, tubeworms, and mussels, but no reports about the general antifouling effect of polygodial have been communicated before. To probe the structural and chemical basis for antifouling activity, a library of 11 polygodial analogues was prepared by semisynthesis. The library was designed to yield derivatives with ranging polarities and the ability to engage in both covalent and noncovalent interactions, while still remaining within the drimane sesquiterpene scaffold. The prepared compounds were screened against 14 relevant marine micro- and macrofouling species. Several of the polygodial analogues displayed inhibitory activities at sub-microgram/mL concentrations. These antifouling effects were most pronounced against the macrofouling ascidian Ciona savignyi and the barnacle Balanus improvisus, with inhibitory activities observed for selected compounds comparable or superior to several commercial antifouling products. The inhibitory activity against the microfouling bacteria and microalgae was reversible and significantly less pronounced than for the macrofoulers. This study illustrates that the macro- and microfoulers are targeted by the compounds via different mechanisms.
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| 29. |
- Moodie, Lindon W. K., et al.
(author)
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Synthetic analogs of stryphnusin isolated from the marine sponge : Stryphnus fortis inhibit acetylcholinesterase with no effect on muscle function or neuromuscular transmission
- 2016
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In: Organic and biomolecular chemistry. - : Royal Society of Chemistry (RSC). - 1477-0520 .- 1477-0539. ; 14:47, s. 11220-11229
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Journal article (peer-reviewed)abstract
- The marine secondary metabolite stryphnusin (1) was isolated from the boreal sponge Stryphnus fortis, collected off the Norwegian coast. Given its resemblance to other natural acetylcholinesterase antagonists, it was evaluated against electric eel acetylcholinesterase and displayed inhibitory activity. A library of twelve synthetic phenethylamine analogs, 2a-7a and 2b-7b, containing tertiary and quaternary amines respectively were synthesized to investigate the individual structural contributions to the activity. Compound 7b was the strongest competitive inhibitor of both acetylcholinesterase and butyrylcholinesterase with IC50 values of 57 and 20 μM, respectively. This inhibitory activity is one order of magnitude higher than the positive control physostigmine, and is comparable with several other marine acetylcholinesterase inhibitors. The physiological effect of compound 7b on muscle function and neuromuscular transmission was studied and revealed a selective mode of action at the investigated concentration. This data is of importance as the interference of therapeutic acetylcholinesterase inhibitors with neuromuscular transmission can be problematic and lead to unwanted side effects. The current findings also provide additional insights into the structure-activity relationship of both natural and synthetic acetylcholinesterase inhibitors.
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| 30. |
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| 31. |
- Nicholls, Ian A., et al.
(author)
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Can we rationally design molecularly imprinted polymers?
- 2001
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In: Analytica Chimica Acta. ; 435:1, s. 9-18
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Journal article (peer-reviewed)abstract
- The nearly exponential growth in the molecular imprinting literature has to a large extent been fuelled by an increasing awareness of the potential of molecular imprinting based technologies. Despite the acceptance of the technique by cognate disciplines and the demonstration of its usefulness in a number of enabling technologies, relatively little is known about the molecular level events underlying the imprinting process and subsequent recognition events. What rules govern imprint formation? Can we use such rules to rationally design molecularly imprinted polymers?
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| 32. |
- Nicholls, Ian A., et al.
(author)
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Molecularly imprinted polymers: unique possibilities for environmental monitoring
- 2002
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In: Proceedings of Kalmar Eco-Tech'01 : conference on leachate and waste water treatment with high-tech and natural systems : the 3rd International Conference on the Establishment of Cooperation Between Companies/Institutions in the Nordic Countries and the Countries in the Baltic Sea Region : November 26 to 28, 2001 Kalmar, Sweden. - : Högskolan i Kalmar. ; , s. 285-288, s. 285-288
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Conference paper (other academic/artistic)
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| 33. |
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| 34. |
- Rosengren-Holmberg, Jenny P., et al.
(author)
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Synthesis and ligand recognition of paracetamol selective polymers: semi-covalent versus non-covalent molecular imprinting.
- 2009
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In: Organic and biomolecular chemistry. - : Royal Society of Chemistry (RSC). - 1477-0520 .- 1477-0539. ; 7, s. 3148-3155
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Journal article (peer-reviewed)abstract
- Three molecular imprinting strategies, each based upon a series of ethylene glycol dimethacrylate (EGDMA) cross-linked co-polymers, have been used to produce materials selective for the commonly used analgesic and antipyretic agent paracetamol (p-acetaminophen or 4-acetamidophenol) (1). The polymers were synthesised using either a semi-covalent imprinting strategy based upon 4-acetamidophenyl-(4-vinylphenyl) carbonate (4) or a non-covalent strategy based on methacrylic acid (MAA) as the functional monomer, or by employing a combination of these strategies. Radioligand binding studies demonstrated low template affinity in polymers offering only a single electrostatic interaction point for recognition via the phenolic residue in the template, whereas binding was substantially increased upon the introduction of a second binding mode, namely interaction at the acetamide moiety. HPLC analyses revealed no imprinting effect in the purely semi-covalent system, and only a minor effect in the purely non-covalent systems. However, a pronounced imprinting effect was demonstrated for polymers prepared by a combination of semi-covalent and non-covalent imprinting. This study illustrates a limitation of both the non-covalent and the semi-covalent strategies when it comes to achieving imprinted selectivity for small and poorly functionalised templates such as paracetamol. Parallels with conclusions from studies with antibodies are discussed.
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| 35. |
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| 36. |
- Sidenbladh, Hedvig, et al.
(author)
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Comparing future situation pictures
- 2005
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In: 2005 7th International Conference on Information Fusion (FUSION), Vols 1 and 2. ; , s. 963-968
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Conference paper (peer-reviewed)
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| 37. |
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| 38. |
- Sivertsen, A, et al.
(author)
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Synthetic cationic antimicrobial peptides bind with their hydrophobic parts to drug site II of human serum albumin
- 2014
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In: BMC Structural Biology. - : Springer Science and Business Media LLC. - 1472-6807. ; 14:1
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Journal article (peer-reviewed)abstract
- Background Many biologically active compounds bind to plasma transport proteins, and this binding can be either advantageous or disadvantageous from a drug design perspective. Human serum albumin (HSA) is one of the most important transport proteins in the cardiovascular system due to its great binding capacity and high physiological concentration. HSA has a preference for accommodating neutral lipophilic and acidic drug-like ligands, but is also surprisingly able to bind positively charged peptides. Understanding of how short cationic antimicrobial peptides interact with human serum albumin is of importance for developing such compounds into the clinics. Results The binding of a selection of short synthetic cationic antimicrobial peptides (CAPs) to human albumin with binding affinities in the μM range is described. Competitive isothermal titration calorimetry (ITC) and NMR WaterLOGSY experiments mapped the binding site of the CAPs to the well-known drug site II within subdomain IIIA of HSA. Thermodynamic and structural analysis revealed that the binding is exclusively driven by interactions with the hydrophobic moieties of the peptides, and is independent of the cationic residues that are vital for antimicrobial activity. Both of the hydrophobic moieties comprising the peptides were detected to interact with drug site II by NMR saturation transfer difference (STD) group epitope mapping (GEM) and INPHARMA experiments. Molecular models of the complexes between the peptides and albumin were constructed using docking experiments, and support the binding hypothesis and confirm the overall binding affinities of the CAPs. Conclusions The biophysical and structural characterizations of albumin-peptide complexes reported here provide detailed insight into how albumin can bind short cationic peptides. The hydrophobic elements of the peptides studied here are responsible for the main interaction with HSA. We suggest that albumin binding should be taken into careful consideration in antimicrobial peptide studies, as the systemic distribution can be significantly affected by HSA interactions.
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| 39. |
- Stensen, Wenche, et al.
(author)
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Short cationic antimicrobial peptides display superior antifungal activities toward Candidiasis and Onychomycosis in comparison with Terbinafine and Amorolfine
- 2016
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In: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 13:10, s. 3595-3600
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Journal article (peer-reviewed)abstract
- Novel antifungals are in high demand due to the challenges associated with resistant, persistent, and systemic fungal infections. Synthetic mimics of antimicrobial peptides are emerging as a promising class of compounds for antifungal treatment. In the current study, five synthetic cationic antimicrobial tripeptides were evaluated as antifungal therapeutics against 24 pathogenic strains of fungi. Three of the peptides displayed strong general antifungal properties at low micromolar inhibitory concentrations. The most promising peptide, compound 5, was selected and evaluated as an antifungal remedy for Candida albicans candidiasis in a human skin model and for the treatment of Trichophyton rubrum induced onychomycosis in an infected human nail model. Compound 5 was shown to display antifungal properties and a rapid mode of action superior to those of both the commercial comparators Loceryl and Lamisil. Compound 5 was also active against a clinical isolate of Candida albicans with acquired fluconazole resistance.
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| 40. |
- Svendsen, John, et al.
(author)
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Very Short and Stable Lactoferricin-Derived Antimicrobial Peptides : Design Principles and Potential Uses
- 2019
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In: Accounts of Chemical Research. - : American Chemical Society (ACS). - 0001-4842 .- 1520-4898. ; 52:3, s. 749-759
-
Journal article (peer-reviewed)abstract
- ConspectusThe alarming rate at which micro-organisms are developing resistance to conventional antibiotics represents one of the global challenges of our time. There is currently ample space in the antibacterial drug pipeline, and scientists are trying to find innovative and novel strategies to target the microbial enemies. Nature has remained a source of inspiration for most of the antibiotics developed and used, and the immune molecules produced by the innate defense systems, as a first line of defense, have been heralded as the next source of antibiotics. Most living organisms produce an arsenal of antimicrobial peptides (AMPs) to rapidly fend off intruding pathogens, and several different attempts have been made to transform this versatile group of compounds into the next generation of antibiotics. However, faced with the many hurdles of using peptides as drugs, the success of these defense molecules as therapeutics remains to be realized. AMPs derived from the proteolytic degradation of the innate defense protein lactoferrin have been shown to display several favorable antimicrobial properties. In an attempt to investigate the biological and pharmacological properties of these much shorter AMPs, the sequence dependence was investigated, and it was shown, through a series of truncation experiments, that these AMPs in fact can be prepared as tripeptides, with improved antimicrobial activity, via the incorporation of unnatural hydrophobic residues and terminal cappings. In this Account, we describe how this class of promising cationic tripeptides has been developed to specifically address the main challenges limiting the general use of AMPs. This has been made possible through the identification of the antibacterial pharmacophore and via the incorporation of a range of unnatural hydrophobic and cationic amino acids. Incorporation of these residues at selected positions has allowed us to extensively establish how these compounds interact with the major proteolytic enzymes trypsin and chymotrypsin and also the two major drug-binding plasma proteins serum albumin and α-1 glycoprotein. Several of the challenges associated with using AMPs relate to their size, susceptibility to rapid proteolytic degradation, and poor oral bioavailability. Our studies have addressed these issues in detail, and the results have allowed us to effectively design and prepare active and metabolically stable AMPs that have been evaluated in a range of functional settings. The optimized short AMPs display inhibitory activities against a plethora of micro-organisms at low micromolar concentrations, and they have been shown to target resistant strains of both bacteria and fungi alike with a very rapid mode of action. Our Account further describes how these compounds behave in in vivo experiments and highlights both the challenges and possibilities of the intriguing compounds. In several areas, they have been shown to exhibit comparable or superior activity to established antibacterial, antifungal, and antifouling commercial products. This illustrates their ability to effectively target and eradicate various microbes in a variety of settings ranging from the ocean to the clinic.
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| 41. |
- Svenson, Johan, et al.
(author)
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1H-nuclear magnetic resonance study of the molecular imprinting of (-)-nicotine : template self-association, a molecular basis for cooperative ligand binding
- 2004
-
In: Journal of Chromatography A. - : Elsevier. - 0021-9673 .- 1873-3778. ; 1024:1-2, s. 39-44
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Journal article (peer-reviewed)abstract
- In the present study, the interactions of components in a (−)-nicotine molecular imprinting polymerization mixture have been studied by NMR spectroscopy. The dissociation constants for complexation of template by a functional monomer analogue, acetic acid, have been determined. Nicotine was shown to self-associate at concentrations comparable to those used in previous molecular imprinting studies (app Kdiss=0.082 M in CDCl3 at 298 K). The extent of self-association was enhanced by the presence of acetic acid. Previous studies on (−)-nicotine–imprinted methacrylic acid–ethylene dimethacrylate co-polymers suggested the involvement of recognition sites for template–template complexes. Collectively these results provide the first direct evidence for the presence of template–template complexes, and support the previously hypothesized basis for cooperative ligand recognition events in this polymer system.
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| 42. |
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| 43. |
- Svenson, Johan
(author)
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Alcohol consumption and harm among adolescents in Sweden : is smuggled alcohol more harmful?
- 2012
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In: Journal of Child & Adolescent Substance Abuse. - 1067-828X .- 1547-0652. ; 21:2, s. 167-180
-
Journal article (peer-reviewed)abstract
- As a consequence of Sweden joining the European Union, privately imported alcohol is increasingly sold within illegal contexts (i.e., smuggled alcohol). One implication of the smuggled alcohol is that alcohol becomes more available to underage drinkers. In the Swedish debate, smuggled alcohol has been formulated as a youth problem. The aim of this article is to examine the relationship between consumption of smuggled alcohol and alcohol-related harm among adolescents in Sweden. Data on consumption of smuggled alcohol were obtained from monthly surveys, and data on harm originates from the National Board of Health and Welfare. The analysis was made by means of time-series analysis (ARIMA models). The results highlight the importance of overall consumption per se and not the type of alcohol (illegal or not) consumed.
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| 44. |
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| 45. |
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| 46. |
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| 47. |
- Svenson, Johan
(author)
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På jakt efter nya läkemedel i Ishavet
- 2016
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In: Naturvetare. - : Naturvetarna. - 2000-2424. ; 6, s. 24-28
-
Journal article (pop. science, debate, etc.)abstract
- Ungefär en tredjedel av alla läkemedel har sin källa i naturen. Forskaren Johan Svenson skriver själv om sin expedition i Arktis, där forskarna samlar in alger och andra organismer i sökandet efter nya molekyler, som till exempel kan bli ny antibiotika.
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| 48. |
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| 49. |
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| 50. |
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