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141.
Eszter Kozma P. Suresh Jayasekara Lucia Squarcialupi Silvia Paoletta Stefano Moro Stephanie Federico Giampiero Spalluto Kenneth A. Jacobson 《Bioorganic & medicinal chemistry letters》2013,23(1):26-36
Interest is increasing in developing fluorescent ligands for characterization of adenosine receptors (ARs), which hold a promise of usefulness in the drug discovery process. The size of a strategically labeled AR ligand can be greatly increased after the attachment of a fluorophore. The choice of dye moiety (e.g. Alexa Fluor 488), attachment point and linker length can alter the selectivity and potency of the parent molecule. Fluorescent derivatives of adenosine agonists and antagonists (e.g. XAC and other heterocyclic antagonist scaffolds) have been synthesized and characterized pharmacologically. Some are useful AR probes for flow cytometry, fluorescence correlation spectroscopy, fluorescence microscopy, fluorescence polarization, fluorescence resonance energy transfer, and scanning confocal microscopy. Thus, the approach of fluorescent labeled GPCR ligands, including those for ARs, is a growing dynamic research field. 相似文献
142.
Luigi Piero Stasi Roberto Artusi Clara Bovino Benedetta Buzzi Luca Canciani Gianfranco Caselli Fabrizio Colace Paolo Garofalo Silvia Giambuzzi Patrice Larger Ornella Letari Stefano Mandelli Lorenzo Perugini Sabrina Pucci Matteo Salvi PierLuigi Toro 《Bioorganic & medicinal chemistry letters》2013,23(9):2653-2658
Starting from a orexin 1 receptor selective antagonist 4,4-disubstituted piperidine series a novel potent 5-azaspiro[2.4]heptane dual orexin 1 and orexin 2 receptor antagonist class has been discovered. SAR and Pharmacokinetic optimization of this series is herein disclosed. Lead compound 15 exhibits potent activity against orexin 1 and orexin 2 receptors along with low cytochrome P450 inhibition potential, good brain penetration and oral bioavailability in rats. 相似文献
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144.
Three Cocconeis Ehrenberg species, epiphytic on the leaves of Posidonia oceanica (L.) Delile, were studied by light and electron microscopy. A new species, C. pseudonotata, is described which is closely related to C. notata Petit and C. diruptoides Hustedt. Gross morphology and the presence of a sigmoid raphe and sternum are the characters shared by the three species, whereas the central areas of sternum and raphe-sternum valves, and the stria and areola densities are the main distinctive characters for the species when observed by light microscopy. Scanning and transmission electron microscopic observations revealed that the fine structure of areolae must be also considered in order to identify the species. Comparison among the three species has been carried out by observations on material from our samples, as well as on the type material of C. diruptoides and cleaned samples from the Hustedt collection. The study also provides new information on the geographical distribution of these species. 相似文献
145.
Annamaria Sinisi Barbara Calcinai Carlo Cerrano Henny A. Dien Angela Zampella Claudio D’Amore Barbara Renga Stefano Fiorucci Orazio Taglialatela-Scafati 《Bioorganic & medicinal chemistry》2013,21(17):5332-5338
Chemical investigation of an Indonesian specimen of Theonella swinhoei afforded the new dimeric macrolides isoswinholide B (5) and swinholide K (6), along with the known swinholides A (1), B (2) and D (3) and isoswinholide A (4). Isoswinholide B showed an unprecedented 21/19′ lactonization pattern, while swinholide K included an sp2 methylene attached at C-4 and an additional oxymethine group at C-5, whose configuration has been determined through application of J-based configuration analysis. The isolated swinholides (1–6), with the exception of isoswinholide B, showed a cytotoxic activity on HepG2 (hepatocarcinoma cell line) in the nanomolar range. 相似文献
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148.
Anna Marchiani Stefano Mammi Giuliano Siligardi Rohanah Hussain Isabella Tessari Luigi Bubacco Giovanna Delogu Davide Fabbri Maria A. Dettori Daniele Sanna Sonia Dedola Pier A. Serra Paolo Ruzza 《Amino acids》2013,45(2):327-338
Curcumin, a dietary polyphenol, has shown a potential to act on the symptoms of neurodegenerative disorders, including Alzheimer’s and Parkinson’s diseases, as a consequence of its antioxidant, anti-inflammatory and anti-protein aggregation properties. Unfortunately, curcumin undergoes rapid degradation at physiological pH into ferulic acid, vanillin and dehydrozingerone, making it an unlikely drug candidate. Here, we evaluated the ability of some curcumin by-products: dehydrozingerone (1), its O-methyl derivative (2), zingerone (3), and their biphenyl analogues (4–6) to interact with α-synuclein (AS), using CD and fluorescence spectroscopy. In addition, the antioxidant properties and the cytoprotective effects in rat pheochromocytoma (PC12) cells prior to intoxication with H2O2, MPP+ and MnCl2 were examined while the Congo red assay was used to evaluate the ability of these compounds to prevent aggregation of AS. We found that the biphenyl zingerone analogue (6) interacts with high affinity with AS and also displays the best antioxidant properties while the biphenyl analogues of dehydrozingerone (4) and of O-methyl-dehydrozingerone (5) are able to partially inhibit the aggregation process of AS, suggesting the potential role of a hydroxylated biphenyl scaffold in the design of AS aggregation inhibitors. 相似文献
149.
Barbara Zambelli Katarzyna Banaszak Anna Merloni Agnieszka Kiliszek Wojciech Rypniewski Stefano Ciurli 《Journal of biological inorganic chemistry》2013,18(8):1005-1017
Urease is a nickel-dependent enzyme that plays a critical role in the biogeochemical nitrogen cycle by catalyzing the hydrolysis of urea to ammonia and carbamate. This enzyme, initially synthesized in the apo form, needs to be activated by incorporation of two nickel ions into the active site, a process driven by the dimeric metallochaperone UreE. Previous studies reported that this protein can bind different metal ions in vitro, beside the cognate Ni(II). This study explores the metal selectivity and affinity of UreE from Sporosarcina pasteurii (Sp, formerly known as Bacillus pasteurii) for cognate [Ni(II)] and noncognate [Zn(II)] metal ions. In particular, the thermodynamic parameters of SpUreE Ni(II) and Zn(II) binding have been determined using isothermal titration calorimetry. These experiments show that two Ni(II) ions bind to the protein dimer with positive cooperativity. The high-affinity site involves the conserved solvent-exposed His100 and the C-terminal His145, whereas the low-affinity site comprises also the C-terminal His147. Zn(II) binding to the protein, occurring in the same protein regions and with similar affinity as compared to Ni(II), causes metal-driven dimerization of the protein dimer. The crystal structure of the protein obtained in the presence of equimolar amounts of both metal ions indicates that the high-affinity metal binding site binds Ni(II) preferentially over Zn(II). The ability of the protein to select Ni(II) over Zn(II) was confirmed by competition experiments in solution as well as by analysis of X-ray anomalous dispersion data. Overall, the thermodynamics and structural parameters that modulate the metal ion specificity of the different binding sites on the protein surface of SpUreE have been established. 相似文献
150.
Landscape context determinants to plant diversity in the permanent meadows of Southern European Alps
Antonio T. Monteiro Francesco Fava João Gonçalves Alfredo Huete Fausto Gusmeroli Gilberto Parolo Donatela Spano Stefano Bocchi 《Biodiversity and Conservation》2013,22(4):937-958
In the Southern Alps, the role of landscape context on meadows plant diversity was evaluated using a multi-model information theoretic approach and five competing hypotheses of landscape context factors: habitat quality (H1), matrix quality (H2), habitat change (H3), matrix quality change (H4) and topography-environmental conditions (H5)- measured at three spatial scales (125, 250 and 500 m). Shannon diversity index and species richness represented plant diversity obtained in 34 plots (100 m2 size). Landscape context affected plant diversity measures differently. Matrix quality change at larger scale (500 m) was the most supported hypothesis explaining Shannon diversity index, while species richness responded mostly to topography-environmental conditions in the immediate surroundings (125 m). No effects of present-day habitat and matrix quality (H1 and H2) were found. Matrix quality change affected positively Shannon diversity index through an effect of landscape neighbourhood context on farming management practices. Due to the importance of exposure and inclination of slopes, topography-environmental conditions influenced species richness mostly through energy-driven processes and farming management strategies. In terms of scale, matrix quality change was the strongest hypothesis explaining Shannon diversity index at all scales, while the underlying process affecting species richness changed with scale (H5 or H3). Overall, landscape context explained only 25–28 % of the variation in plant diversity, suggesting that landscape management may support biodiversity conservation when comprised in a global strategy including farming practices. In the study area, change in landscape diversity may be a good indicator for Shannon diversity index and south-eastern facing meadows should be preserved. 相似文献