| 1. |
- Cahill, P. L., et al.
(författare)
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Creating New Antifoulants Using the Tools and Tactics of Medicinal Chemistry
- 2024
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Ingår i: Accounts of Chemical Research. - : American Chemical Society. - 0001-4842 .- 1520-4898. ; 57:3, s. 399-
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Tidskriftsartikel (refereegranskat)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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| 2. |
- Moodie, Lindon W. K., et al.
(författare)
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Design and Biological Evaluation of Antifouling Dihydrostilbene Oxime Hybrids
- 2018
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Ingår i: Marine Biotechnology. - : Springer Science and Business Media LLC. - 1436-2228 .- 1436-2236. ; 20:2, s. 257-267
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Tidskriftsartikel (refereegranskat)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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| 3. |
- Trepos, R., et al.
(författare)
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Evaluation of cationic micropeptides derived from the innate immune system as inhibitors of marine biofouling
- 2015
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Ingår i: Biofouling. - : Informa UK Limited. - 0892-7014 .- 1029-2454. ; 31:4, s. 393-403
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Tidskriftsartikel (refereegranskat)abstract
- A series of 13 short synthetic amphiphilic cationic micropeptides, derived from the antimicrobial iron-binding innate defence protein lactoferrin, have been evaluated for their capacity to inhibit the marine fouling process. The whole biofouling process was studied and microfouling organisms such as marine bacteria and microalgae were included as well as the macrofouling barnacle Balanus improvisus. In total 19 different marine fouling organisms (18 microfoulers and one macrofouler) were included and both the adhesion and growth of the microfoulers were investigated. It was shown that the majority of the peptides inhibited barnacle cyprid settlement via a reversible nontoxic mechanism, with IC50 values as low as 0.5 mu g ml(-1). Six peptides inhibited adhesion and growth of microorganisms. Two of these were particularly active against the microfoulers with MIC-values ranging between 0.01 and 1 mu g ml(-1), which is comparable with the commercial reference antifoulant SeaNine.
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| 4. |
- Abi Nassif, L., et al.
(författare)
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Reduction of potential ennoblement of stainless steel in natural seawater by an ecofriendly biopolymer
- 2020
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Ingår i: Journal of Environmental Chemical Engineering. - : Elsevier Ltd. - 2213-3437. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- The effect of biofilm formation on passive stainless steel in seawater environments is of primary importance since it leads to potential ennoblement of surfaces and subsequently to localized corrosion such as pitting and crevice corrosion. This study aims at developing an ecofriendly alginate biopolymer containing both non-toxic calcium and a limited amount of biocidal zinc ions which inhibits this effect. For this purpose, calcium alginate containing less than 1 % of zinc ions localized in the vicinity of the steel surface in natural and renewed seawater is demonstrated to reduce significantly the ennoblement process of steel. After 1 month of immersion, a mass loss of only 4 % of the active material is observed authorizing thereby long-term protection of steel in real environment.
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| 5. |
- Davis, R. A., et al.
(författare)
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Evaluation of natural resveratrol multimers as marine antifoulants
- 2023
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Ingår i: Biofouling. - : Taylor and Francis Ltd.. - 0892-7014 .- 1029-2454. ; 39:8, s. 775-784
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Tidskriftsartikel (refereegranskat)abstract
- In the current study we investigate the antifouling potential of three polyphenolic resveratrol multimers (-)-hopeaphenol, vaticanol B and vatalbinoside A, isolated from two species of Anisoptera found in the Papua New Guinean rainforest. The compounds were evaluated against the growth and settlement of eight marine microfoulers and against the settlement and metamorphosis of Amphibalanus improvisus barnacle cyprids. The two isomeric compounds (-)-hopeaphenol and vaticanol B displayed a high inhibitory potential against the cyprid larvae metamorphosis at 2.8 and 1.1 mu M. (-)-Hopeaphenol was also shown to be a strong inhibitor of both microalgal and bacterial adhesion at submicromolar concentrations with low toxicity. Resveratrol displayed a lower antifouling activity compared to the multimers and had higher off target toxicity against MCR-5 fibroblasts. This study illustrates the potential of natural products as a valuable source for the discovery of novel antifouling leads with low toxicity.
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| 6. |
- Grant, T. M., et al.
(författare)
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Towards eco-friendly marine antifouling biocides-Nature inspired tetrasubstituted 2,5-diketopiperazines
- 2022
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697. ; 812
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Tidskriftsartikel (refereegranskat)abstract
- Marine biofouling plagues all maritime industries at vast economic and environmental cost. Previous and most current methods to control biofouling have employed highly persistent toxins and heavy metals, including tin, copper, and zinc. These toxic methods are resulting in unacceptable environmental harm and are coming under immense regulatory pressure. Eco-friendly alternatives are urgently required to effectively mitigate the negative consequence of biofouling without causing collateral harm. Amphiphilic micropeptides have recently been shown to exhibit excellent broad-spectrum antifouling activity, with a non-toxic mode of action and innate biodegradability. The present work focused on incorporating the pharmacophore derived from amphiphilic micropeptides into a 2,5-diketopiperazine (DKP) scaffold. This privileged structure is present in a vast number of natural products, including marine natural product antifoulants, and provides advantages of synthetic accessibility and adaptability. A novel route to symmetrical tetrasubstituted DKPs was developed and a library of amphiphilic 2,5-DKPs were subsequently synthesised. These biodegradable compounds were demonstrated to be potent marine antifoulants displaying broad-spectrum activity in the low micromolar range against a range of common marine fouling organisms. The outcome of planned coating and field trials will dictate the future development of the lead compounds.
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| 7. |
- Misko, T. P., et al.
(författare)
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Characterization of nitrotyrosine as a biomarker for arthritis and joint injury
- 2013
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 21:1, s. 151-156
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To characterize the utility of nitrotyrosine (NT) as a biomarker for arthritis and joint injury. Design: Synovial fluid, plasma, and urine from patients diagnosed with osteoarthritis (OA), rheumatoid arthritis (RA), anterior cruciate ligament (ACL) injury, meniscus injury and pseudogout, and knee-healthy volunteers were analyzed for concentrations of NT, nitrate and nitrite (NOx), matrix metalloproteinase (MMP)-3, MMP-1, MMP-9, more than 40 chemokines and cytokines. Results: In OA, plasma and synovial fluid NT were increased versus healthy volunteers. Synovial fluid to plasma NT ratios were elevated in OA patients. Synovial fluid from patients with ACL and meniscus injury and pseudogout had increased levels of NT (P < 0.001). In these samples, NT levels significantly correlated with ARGS-aggrecan neoepitope generated by aggrecanase cleavage of aggrecan (P <= 0.001), cross-linked C-telopeptides of type II collagen (P < 0.001), MMP-1 (P = 0.008), and MMP-3 (P <= 0.001). In RA, plasma NT decreased following 6 months of anti-tumor necrosis factor (TNF) treatment. For every 1.1% change in log(10) NT, there was a 1.0% change in the log(10) disease activity scores (DAS28-3 CRP). Both predicted and observed DAS28-3 CRP showed a robust linear relationship with NT. RA plasma NT positively correlated with CRP, MMP-3 and interferon gamma-induced protein 10. Conclusions: NT may serve as a useful biomarker for arthritis and joint injury. In RA, NT is highly correlated with several biomarkers and clinical correlates of disease activity and responds to anti-TNF therapy. (C) 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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| 8. |
- Moodie, Lindon W. K., et al.
(författare)
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Prevention of Marine Biofouling Using the Natural Allelopathic Compound Batatasin-Ill and Synthetic Analogues
- 2017
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Ingår i: Journal of Natural Products. - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025. ; 80:7, s. 2001-2011
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Tidskriftsartikel (refereegranskat)abstract
- The current study reports the first comprehensive evaluation of a class of allelopathic terrestrial natural products as antifoulants in a marine setting. To investigate the antifouling potential of the natural dihydrostilbene scaffold, a library of 22 synthetic dihydrostilbenes with varying substitution patterns, many of which occur naturally in terrestrial plants, were prepared and assessed for their antifouling capacity. The compounds were evaluated in an extensive screen against 16 fouling marine organisms. The dihydrostilbene scaffold was shown to possess powerful general antifouling effects against both marine microfoulers and macrofoulers with inhibitory activities at low concentrations. The species of microalgae examined displayed a particular sensitivity toward the evaluated compounds at low ng/mL concentrations. It was shown that several of the natural and synthetic compounds exerted their repelling activities via nontoxic and reversible mechanisms. The activities of the most active compounds such as 3,5-dimethoxybibenzyl (5), 3,4-dimethoxybibenzyl (9), and 3-hyolroxy-3',4,5'-trirnethoxybibenzyl (20) were comparable to the commercial antifouling booster biocide. Sea-nine, which was employed as a positive control. The investigation of terrestrial allelopathic natural products to counter marine fouling represents a novel strategy for the design of "green" antifouling technologies, and these compounds offer a potential alternative to traditional biocidal antifoulants.
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| 9. |
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| 10. |
- Witthaut, Jörg, et al.
(författare)
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Determining Clinically Important Changes in Range of Motion in Patients with Dupuytren's Contracture : Secondary Analysis of the Randomized, Double-Blind, Placebo-Controlled CORD I Study
- 2011
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Ingår i: Clinical drug investigation. - 1173-2563 .- 1179-1918. ; 31:11, s. 791-798
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVE: Injectable collagenase Clostridium histolyticum is efficacious in correcting Dupuytren's contracture as assessed by changes in the angle of contracture and range of motion (ROM). However, clinically important changes in ROM have not been evaluated in depth. The objective of this secondary analysis of the CORD I trial was to identify severity levels using baseline ROM, estimate a clinically important difference (CID) for ROM, and link the results to collagenase treatment and patient satisfaction. METHODS: In the CORD I trial, patients with Dupuytren's disease and joint contractures ≥20° were randomized to receive a maximum of three collagenase 0.58 mg or placebo injections into the cord of the affected hand at 30-day intervals. The primary endpoint was reduction in contracture to ≤5° 30 days after the last injection (day 30). The secondary endpoints, which are reported in this analysis, were ROM, physician- and patient-rated severity ('normal', 'mild', 'moderate', 'severe') and improvement, and treatment satisfaction. Linear regression was used to model data for severity classification and CID estimation for ROM based on physician and patient ratings. RESULTS: At baseline, mean ROM was 43.9° in the collagenase-treated joints (n = 197) and 45.3° in the placebo-treated joints (n = 102). On day 30, mean ROM was 80.7° in the collagenase-treated joints and 49.5° in the placebo-treated joints. The mean increase in ROM was 36.7° in the collagenase-treated joints (p < 0.001) and 4.0° in the placebo-treated joints (not significant). The estimated CID for ROM was 13.5° (95% CI 11.9, 15.1), reflecting a one-category change in severity. The mean increase in ROM exceeded the CID in the collagenase-treated joints but not in the placebo-treated joints; the difference between collagenase treatment and placebo in the mean increase in ROM also exceeded the CID, implying that the improvement with collagenase was clinically relevant. The severity classification for ROM was: ≥67.0° ('normal'), ≥54.3 and <67.0° ('mild'), ≥41.6 and <54.3° ('moderate'), and <41.6° ('severe'). More collagenase- than placebo-treated patients achieved 'normal' (81% vs 25%; p < 0.0001) status, and more collagenase- than placebo-treated patients reported being 'very/quite satisfied' (87% vs 32%; p < 0.001). CONCLUSION: Injectable collagenase significantly improves ROM and treatment satisfaction versus placebo. ROM improvements are clinically relevant as well as statistically significant. These data support the potential need to include ROM and physician- and patient-rated severity and satisfaction as standard assessments for Dupuytren's contracture treatment outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00528606; other study identification number: AUX-CC-857 (Auxilium Pharmaceuticals, Inc.).
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