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111.
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
112.
Cristhiane Caroline Ferrari Silvia Pimentel Marconi Germer José Maurício de Aguirre 《Drying Technology》2013,31(2):154-163
The purpose of this work was to study the effects of spray-drying conditions on the physicochemical characteristics of blackberry powder using a central composite rotatable design. Inlet air temperature (140–180°C) and maltodextrin concentration (5–25%) were employed as independent variables. Moisture content, hygroscopicity, anthocyanin retention, color, powder morphology, and particle size were analyzed. A higher inlet air temperature significantly increased the hygroscopicity of the powder, decreased its moisture content, and led to the formation of larger particles with smooth surfaces. Powders produced with higher maltodextrin concentrations were less hygroscopic, slightly lighter and less red, and had a lower moisture content. Anthocyanin retention was mainly affected by drying temperature due to the heat sensitivity of the pigment. The optimal processing conditions were an inlet air temperature of 140–150°C and maltodextrin concentration of 5–7%. Overall, these results indicate that good quality powders can be obtained by spray drying, with potential applications for the food industry. 相似文献
113.
Giuseppe Spoto Silvia Bordiga Domenica Scarano Adriano Zecchina 《Catalysis Letters》1992,13(1-2):39-44
In this note an exchange procedure of the acidic protons of H-ZSM5 by CuI ions through reaction with CuCl in the gas phase is described. In the so obtained CuI-ZSM5 exchanged zeolite the CuI ions are in well defined configuration and form with NO mono and di-nitrosyl complexes of high structural and spectroscopic quality. The CuI(NO)2 species are transformed at RT into CuII(NO)X (X=O– and/or NO
2
–
) species which could represent an intermediate in NO decomposition. 相似文献
114.
Silvia F. Moya Ruth L. Martins Antje Ota Edward L. Kunkes Malte Behrens Martin Schmal 《Applied Catalysis A: General》2012
The Pd on α-Al2O3 catalysts with Pd particles in the low nanometer range have been prepared by a sonochemical reduction and a colloidal method, respectively. The two catalysts differ in their particle size, the widths of their particle size distributions and the amount of carbon incorporation in the Pd lattice.The adsorptive properties of the Pd/Al2O3 samples are different as a result of the different preparation methods. The methane adsorption capacity of that sample with smaller particles is lower than that of the catalyst with larger particles and the energy of activation is nearly doubled. DRIFTS and TPD results of CO adsorption supported by transmission electron microscopy data indicate that the PdSON catalyst with smaller and more homogeneous particles than PdCOL is highly dispersed which influences the coupling-hydrogenolysis process.The catalytic activity evidenced the formation of different adspecies during methane coupling and chemisorption on both catalysts. During the hydrogenation the carbon adspecies formed mainly methane at low adsorption temperatures. The significant amount of adsorbed methane at 773 K is governed by the highly active coordination unsaturated sites at the surface. 相似文献
115.
Silvia Carra Germano Gaudenzi Alessandra Dicitore Davide Saronni Maria Celeste Cantone Alice Plebani Anna Ghilardi Maria Orietta Borghi Leo J. Hofland Luca Persani Giovanni Vitale 《International journal of molecular sciences》2021,22(6)
Medullary thyroid carcinoma (MTC) is a tumor deriving from the thyroid C cells. Vandetanib (VAN) and cabozantinib (CAB) are two tyrosine kinase inhibitors targeting REarranged during Transfection (RET) and other kinase receptors and are approved for the treatment of advanced MTC. We aim to compare the in vitro and in vivo anti-tumor activity of VAN and CAB in MTC. The effects of VAN and CAB on viability, cell cycle, and apoptosis of TT and MZ-CRC-1 cells are evaluated in vitro using an MTT assay, DNA flow cytometry with propidium iodide, and Annexin V-FITC/propidium iodide staining, respectively. In vivo, the anti-angiogenic potential of VAN and CAB is evaluated in Tg(fli1a:EGFP)y1 transgenic fluorescent zebrafish embryos by analyzing the effects on the physiological development of the sub-intestinal vein plexus and the tumor-induced angiogenesis after TT and MZ-CRC-1 xenotransplantation. VAN and CAB exert comparable effects on TT and MZ-CRC-1 viability inhibition and cell cycle perturbation, and stimulated apoptosis with a prominent effect by VAN in MZ-CRC-1 and CAB in TT cells. Regarding zebrafish, both drugs inhibit angiogenesis in a dose-dependent manner, in particular CAB shows a more potent anti-angiogenic activity than VAN. To conclude, although VAN and CAB show comparable antiproliferative effects in MTC, the anti-angiogenic activity of CAB appears to be more relevant. 相似文献
116.
Yikai Chen Yang Tan Silvia Tessarini Sanjay Sampath 《Journal of Thermal Spray Technology》2013,22(2-3):110-115
Spray parameters play an important role on the microstructure and properties of plasma-sprayed coatings. Parameters such as spray distance, plasma gas flow and current, raster speed, and spray angle all can be varied. In this paper, an integrated study to investigate the effects and influences of spray angle on properties of yttria-stabilized zirconia coatings was carried out with spray angles of 60°, 75°, and 90° (to the substrate surface). In situ coating property sensor based on beam curvature measurements was used to measure the evolving stress and elastic moduli of the resultant coatings and combined with other characterization tools for thermo-physical property and microstructure analysis, such as laser flash and scanning electron microscopy. The results indicate that the coating with 60° spray angle had the lowest thermal conductivity and more compliant structure. This study seeks to understand the mechanism for this effect and will provide important insight into parametric sensitivities on complex spray parts. 相似文献
117.
Andrea Brenna Silvia Beretta Riccardo Uglietti Luciano Lazzari MariaPia Pedeferri Marco Ormellese 《腐蚀工程科学与技术》2017,52(4):253-260
The criterion used to verify the cathodic protection condition of a structure is based on structure-to-electrolyte potential measurement, which can include an ohmic drop contribution. Among the available techniques, the use of potential probes with internal reference electrode and of corrosion coupons with a so-called soil-access tube represents the most appropriate way to measure the IR-free potential, eliminating the ohmic drop contribution. An alternative is represented by on-off technique if equalising, galvanic or stray currents are not present. Laboratory tests have been carried out in soil-simulating solution on cathodically protected carbon steel in order to evaluate the effectiveness of off-potential for the assessment of cathodic protection. Instant-off potential is not reliable in overprotection condition; moreover, the accuracy of the measurement is strongly influenced by the presence of external current as galvanic or equalising currents. The effect of low-pass filter in the data acquisition system on the potential reading is discussed. 相似文献
118.
Maria Lisa Garavaglia Daniela Giustarini Graziano Colombo Francesco Reggiani Silvia Finazzi Marta Calatroni Lucia Landoni Nicola Marcello Portinaro Aldo Milzani Salvatore Badalamenti Ranieri Rossi Isabella Dalle-Donne 《International journal of molecular sciences》2022,23(5)
Thiols (sulfhydryl groups) are effective antioxidants that can preserve the correct structure of proteins, and can protect cells and tissues from damage induced by oxidative stress. Abnormal levels of thiols have been measured in the blood of patients with moderate-to-severe chronic kidney disease (CKD) compared to healthy subjects, as well as in end-stage renal disease (ESRD) patients on haemodialysis or peritoneal dialysis. The levels of protein thiols (a measure of the endogenous antioxidant capacity inversely related to protein oxidation) and S-thiolated proteins (mixed disulphides of protein thiols and low molecular mass thiols), and the protein thiolation index (the molar ratio of the S-thiolated proteins to free protein thiols in plasma) have been investigated in the plasma or red blood cells of CKD and ESRD patients as possible biomarkers of oxidative stress. This type of minimally invasive analysis provides valuable information on the redox status of the less-easily accessible tissues and organs, and of the whole organism. This review provides an overview of reversible modifications in protein thiols in the setting of CKD and renal replacement therapy. The evidence suggests that protein thiols, S-thiolated proteins, and the protein thiolation index are promising biomarkers of reversible oxidative stress that could be included in the routine monitoring of CKD and ESRD patients. 相似文献
119.
Pablo J. Giraudi Noel Salvoza Deborah Bonazza Carlo Saitta Daniele Lombardo Biagio Casagranda Nicol de Manzini Teresa Pollicino Giovanni Raimondo Claudio Tiribelli Silvia Palmisano Natalia Rosso 《International journal of molecular sciences》2022,23(5)
Fibrosis is the strongest predictor for disease-specific mortality in non-alcoholic fatty liver diseases (NAFLD), but the need for liver biopsy limits its diagnosis. We assessed the performance of plasma ficolin-2 (FCN-2) as a biomarker of fibrosis identified by an in silico discovery strategy. Two hundred and thirty-five morbidly obese (MO) subjects with biopsy-proven NAFLD stratified by fibrosis stage (F0, n = 44; F1, n = 134; F2, n = 46; F3/F4, n = 11) and 40 cirrhotic patients were enrolled. The cohort was subdivided into discovery (n = 76) and validation groups (n = 159). The plasma level of FCN-2 and other candidate markers was determined. FCN-2 was inversely correlated with the stage of liver fibrosis (ρ = −0.49, p < 0.001) independently of steatosis (p = 0.90), inflammation (p = 0.57), and ballooning (p = 0.59). In the global cohort, FCN-2 level decreased significantly in a stepwise fashion from F0/F1 (median 4753 ng/mL) to F2–F3–F4 (2760 ng/mL) and in cirrhotic subjects (1418 ng/mL). The diagnostic performance of FCN-2 in detecting F ≥ 2 was higher than other indexes (APRI, FIB-4) (AUROC 0.82, 0.68, and 0.6, respectively). The accuracy improved when combined with APRI score and HDL values (FCNscore, AUROC 0.85). Overall, the FCN-2 plasma level can accurately discriminate liver fibrosis status (minimal vs. moderate/advanced) significantly improving the fibrosis diagnostic algorithms. 相似文献
120.
Anna Liguori Alessandro De Vita Giulia Rossi Luisa Stella Dolci Silvia Panzavolta Chiara Gualandi Laura Mercatali Toni Ibrahim Maria Letizia Focarete 《International journal of molecular sciences》2022,23(6)
In the clinical management of solid tumors, the possibility to successfully couple the regeneration of injured tissues with the elimination of residual tumor cells left after surgery could open doors to new therapeutic strategies. In this work, we present a composite hydrogel–electrospun nanofiber scaffold, showing a modular architecture for the delivery of two pharmaceutics with distinct release profiles, that is potentially suitable for local therapy and post-surgical treatment of solid soft tumors. The composite was obtained by coupling gelatin hydrogels to poly(ethylene oxide)/poly(butylene terephthalate) block copolymer nanofibers. Results of the scaffolds’ characterization, together with the analysis of gelatin and drug release kinetics, displayed the possibility to modulate the device architecture to control the release kinetics of the drugs, also providing evidence of their activity. In vitro analyses were also performed using a human epithelioid sarcoma cell line. Furthermore, publicly available expression datasets were interrogated. Confocal imaging showcased the nontoxicity of these devices in vitro. ELISA assays confirmed a modulation of IL-10 inflammation-related cytokine supporting the role of this device in tissue repair. In silico analysis confirmed the role of IL-10 in solid tumors including 262 patients affected by sarcoma as a negative prognostic marker for overall survival. In conclusion, the developed modular composite device may provide a key-enabling technology for the treatment of soft tissue sarcoma. 相似文献