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21.
Potent,Metabolically Stable 2‐Alkyl‐8‐(2H‐1,2,3‐triazol‐2‐yl)‐9H‐adenines as Adenosine A2A Receptor Ligands 下载免费PDF全文
Dr. Silvia Pace Dr. Giandomenico Brogin Dr. Maria Antonietta Stasi Dr. Teresa Riccioni Franco Borsini Dr. Francesca Capocasa Dr. Francesco Manera Carlo Tallarico Dr. Pietro Grossi Dr. Federica Vacondio Dr. Michele Bassi Dr. Francesca Bartoccini Dr. Simone Lucarini Dr. Giovanni Piersanti Prof. Giorgio Tarzia Walter Cabri Dr. Patrizia Minetti 《ChemMedChem》2015,10(7):1149-1152
Inhibition of adenosine A2A receptors has been shown to elicit a therapeutic response in preclinical animal models of Parkinson’s disease (PD). We previously identified the triazolo‐9H‐purine, ST1535, as a potent A2AR antagonist. Studies revealed that ST1535 is extensively hydroxylated at the ω‐1 position of the butyl side chain. Here, we describe the synthesis and evaluation of derivatives in which the ω‐1 position has been substituted (F, Me, OH) in order to block metabolism. The stability of the compounds was evaluated in human liver microsomes (HLM), and the affinity for A2AR was determined. Two compounds, (2‐(3,3‐dimethylbutyl)‐9‐methyl‐8‐(2H‐1,2,3‐triazol‐2‐yl)‐9H‐purin‐6‐amine ( 3 b ) and 4‐(6‐amino‐9‐methyl‐8‐(2H‐1,2,3‐triazol‐2‐yl)‐9H‐purin‐2‐yl)‐2‐methylbutan‐2‐ol ( 3 c ), exhibited good affinity against A2AR (Ki=0.4 nM and 2 nM , respectively) and high in vitro metabolic stability (89.5 % and 95.3 % recovery, respectively, after incubation with HLM for two hours). 相似文献
22.
伽利略EPTS中原子钟频率稳定度与噪声类型分析 总被引:3,自引:0,他引:3
本文对伽利略系统实验精确授时中心(EPTS)中四台原子钟的主要特性进行了分析.首先基于原子钟的信号模型和时域上的实验测量数据,用Allan方差对各原子钟的频率稳定度进行了计算与分析.其次运用最小二乘算法对短期和长期的时域稳定度数据进行线性拟合,根据拟合斜率鉴别了影响EPTS中各原子钟的主要噪声类型.实验结果表明,EPTS中具有高短期稳定度的氢原子钟和三台高长期稳定度的铯原子钟满足在GSTB-V1阶段产生实验伽利略系统时间(EGST)的设计要求. 相似文献
23.
Giuseppe Genova Patrizia Iacopini Massimiliano Baldi Annamaria Ranieri Paolo Storchi Luca Sebastiani 《International Journal of Food Science & Technology》2012,47(1):13-23
The effect of temperature and storage time on the phenolic composition and on the antioxidant activity of grape (Vitis vinifera L.) juices made using a red (Sangiovese, SG) and a white (Muscat of Alexandria, MA) variety was studied. Total phenolics, flavonoids, flavan‐3‐ols and hydroxycinnamoyl‐tartrates (HCT) were determined on grape extracts (GE) and juices. Total anthocyanins and anthocyanins composition were measured on GE. The antioxidant activity was assessed by means of two different in vitro tests: scavenging of the stable 2,2‐diphenyl‐1‐picrylhydrazyl radical and the inhibition of tyrosine nitration mediated by authentic peroxynitrite (ONOO?). All the juices were analysed after 24 h and 2 weeks of storage by means of two‐way anova (factors being cultivar and temperature). Anthocyanins were not detected in MA extract, whereas in SG their content was 534 mg malvidin‐equivalent per 100 g of dry matter (d.m.) and malvidin derivatives (glycosylated and coumaroylated) were the most represented (respectively 169 and 41 malvidin‐equivalent per 100 g of d.m.). HCT content of the extracts was higher in SG (overall +33%). Also in grape juices, HCT were lower in MA and in this variety, the trans‐fertaric and cis‐coutaric acids were also undetectable. Cultivar effect proved to be highly significant, while no significant differences in the phenolic composition were observed for storage temperatures (4 and ?20 °C) and cultivar × temperature interaction. However, when statistical analysis was focused on each cultivar, MA was found to be more sensible to storage conditions and a significant reduction in total phenolics (?20%) and flavonoids (?53%) content and in the ONOO? scavenging potential (?32%) was evident after 2 weeks at 4 °C (when compared with the same storage temperature after 24 h). On the contrary, SG juices did not show significant differences among the four storage treatments investigated. These results could be explained suggesting that anthocyanins presence in red grape plays a key role in juice stability. 相似文献
24.
Inulin was used as a prebiotic to improve quality of skim milk fermented by pure cultures of Lactobacillus acidophilus, Lactobacillus rhamnosus, Lactobacillus bulgaricus and Bifidobacterium lactis, binary co-cultures with Streptococcus thermophilus, or a cocktail containing all them. Inulin supplementation to pure cultures lowered the generation time, with particular concern to S. thermophilus and L. acidophilus. The generation time of all micro-organisms decreased in the following order: mono-cultures, co-cultures, cocktail. It was demonstrated a synergism between S. thermophilus and the other strains and a bifidogenic effect of inulin. Enumerations of L. rhamnosus in cocktail markedly decreased compared to co-cultures likely because of greater competition for the same substrates. The results of this work highlight the industrial potential of the cocktail, mainly in terms of fermentation acceleration. 相似文献
25.
Carotenoids from tomatoes inhibit heterocyclic amine formation 总被引:1,自引:0,他引:1
Paola Vitaglione Simona Monti Patrizia Ambrosino Kerstin Skog Vincenzo Fogliano 《European Food Research and Technology》2002,215(2):108-113
Tomatoes are a rich source of antioxidants and they are commonly used for meat cooking in Mediterranean countries. The effects of tomato antioxidants on the formation of carcinogenic/mutagenic heterocyclic amines were investigated. A liquid model system containing as precursors creatinine, glucose and glycine in molar concentrations comparable to those present in bovine meat (chemical model system) was employed. A freeze-dried bovine meat juice (meat juice model system) was also used for some experiments. In both model systems, an inhibiting effect of tomato carotenoid fraction on the formation of imidazoquinolines (IQx, MeIQx and DiMeIQx) was observed. Using carotenoid extract at a concentration of 1000 ppm, inhibitions of 36% and 11% of IQx and MeIQx formation respectively in the chemical system and of 13% of MeIQx and of 5% of 4,8-DiMeIQx in the meat juice system was observed. The effect of the main tomato flavonoid, quercetin, was investigated using the meat juice system. Quercetin gave an inhibition of MeIQx formation between 9% and 57% with a maximum effect of 67% at 10 ppm. 相似文献
26.
Reduction of immunoreactivity of bovine beta-lactoglobulin upon combined physical and proteolytic treatment 总被引:3,自引:0,他引:3
Bonomi F Fiocchi A Frøkiaer H Gaiaschi A Iametti S Poiesi C Rasmussen P Restani P Rovere P 《The Journal of dairy research》2003,70(1):51-59
Bovine beta-lactoglobulin was hydrolyzed with trypsin or chymotrypsin before, during and after treatment at 600 MPa and pH 6.8 for 10 min at 30, 37 and 44 degrees C. The extent of beta-lactoglobulin hydrolysis under pressure was noticeably higher than at atmospheric pressure, particularly when chymotrypsin was used. Addition of proteases at ambient pressure to previously pressure-treated beta-lactoglobulin gave only a modest increase in proteolysis with respect to the untreated protein. Products of enzyme hydrolysis under pressure were separated by reverse-phase HPLC, and were found to be different from those obtained at atmospheric pressure when chymotrypsin was used. The residual immunochemical reactivity of the products of combined pressure-enzyme treatment was assessed on the unresolved hydrolysates by ELISA tests using polyclonal and monoclonal antibodies, and on individual hydrolytic fractions by Western Blotting using sera of paediatric patients allergic to whey proteins in cow milk. The immunoreactivity of the whole hydrolysates was related to their content of residual intact beta-lactoglobulin, and no immunochemical reactivity was found for all the products of chymotrypsin hydrolysis under pressure. The results indicate that chymotrypsin effectively hydrolysed hydrophobic regions of beta-lactoglobulin that were transiently exposed during the pressure treatments and that were not accessible in the native protein or in the protein that had been previously pressure treated. 相似文献
27.
Mohamed Latoui Bahar Aliakbarian Alessandro A. Casazza Mongi Seffen Attilio Converti Patrizia Perego 《Food and Bioproducts Processing》2012,90(4):748-754
The primary objective of this study was to valorized Vitex agnus-castus residues in terms of phenolic compounds. The effects of extraction time (30–360 min), solid to liquid ratio (0.1–0.3 gDryBiomass/mlSolvent), type of solvent and different tissue types (leave, roots and seeds) on total polyphenols, o-diphenols, total flavonoids and anthocyanins were evaluated. The highest total polyphenol (31.5 mgCaffeicAcidEquivalent/gDryBiomass) and o-diphenol (12.4 mgCaffeicAcidEquivalent/gDryBiomass) contents were obtained from methanolic extract of leaves after 180 min using a solid/liquid ratio of 0.1 gDryBiomass/mlSolvent, while total flavonoids, reached a maximum value of 19.4 mgCatechinEquivalent/gDryBiomass after 360 min under the same conditions. Roots of V. agnus-castus were found to be a good source of anthocyanins with the highest yield of 0.62 mgMalvidinEquivalent/gDryBiomass using ethanol as a solvent (180 min and 0.2 gDryBiomass/mlSolvent). The maximum antiradical power (178.5 μlextract/μgDPPH) was exhibited by the methanolic leave extract obtained after 360 min at solid/liquid ratio of 0.3 gDryBiomass/mlSolvent. 相似文献
28.
29.
Andrea Pietro Reverberi Patrizia Bagnerini Luigi Maga Agostino Giacinto Bruzzone 《International Journal of Heat and Mass Transfer》2008,51(21-22):5327-5332
A numerical study on a non-linear hyperbolic diffusion equation is proposed. The Hartree hybrid method combining finite difference techniques with the method of characteristics is used in the presence of discontinuities between initial and boundary conditions. The technique proved to be an useful tool to overcome oscillation problems and spurious solutions in case of strong non-linearities related to both attractive or repulsive interactions between diffusing species. Two different expressions for the diffusion coefficient are used in order to compare our results with the ones obtained in previous studies relying upon the Laplace transform technique and the MacCormack predictor–corrector method. Finally, an analytic approach based on the singular surface theory is proposed to motivate the numerical results and to clarify some controversial aspects concerning the penetration depth of a diffusive front in the presence of interactions. 相似文献
30.