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31.
32.
Structural Determinants of the Selectivity of 3‐Benzyluracil‐1‐acetic Acids toward Human Enzymes Aldose Reductase and AKR1B10 下载免费PDF全文
Dr. Francesc X. Ruiz Alexandra Cousido‐Siah Dr. Sergio Porté Dr. Marta Domínguez Isidro Crespo Chris Rechlin Dr. André Mitschler Prof. Dr. Ángel R. de Lera Dr. María Jesús Martín Dr. Jesús Ángel de la Fuente Prof. Dr. Gerhard Klebe Prof. Dr. Xavier Parés Prof. Dr. Jaume Farrés Dr. Alberto Podjarny 《ChemMedChem》2015,10(12):1989-2003
The human enzymes aldose reductase (AR) and AKR1B10 have been thoroughly explored in terms of their roles in diabetes, inflammatory disorders, and cancer. In this study we identified two new lead compounds, 2‐(3‐(4‐chloro‐3‐nitrobenzyl)‐2,4‐dioxo‐3,4‐dihydropyrimidin‐1(2H)‐yl)acetic acid (JF0048, 3 ) and 2‐(2,4‐dioxo‐3‐(2,3,4,5‐tetrabromo‐6‐methoxybenzyl)‐3,4‐dihydropyrimidin‐1(2H)‐yl)acetic acid (JF0049, 4 ), which selectively target these enzymes. Although 3 and 4 share the 3‐benzyluracil‐1‐acetic acid scaffold, they have different substituents in their aryl moieties. Inhibition studies along with thermodynamic and structural characterizations of both enzymes revealed that the chloronitrobenzyl moiety of compound 3 can open the AR specificity pocket but not that of the AKR1B10 cognate. In contrast, the larger atoms at the ortho and/or meta positions of compound 4 prevent the AR specificity pocket from opening due to steric hindrance and provide a tighter fit to the AKR1B10 inhibitor binding pocket, probably enhanced by the displacement of a disordered water molecule trapped in a hydrophobic subpocket, creating an enthalpic signature. Furthermore, this selectivity also occurs in the cell, which enables the development of a more efficient drug design strategy: compound 3 prevents sorbitol accumulation in human retinal ARPE‐19 cells, whereas 4 stops proliferation in human lung cancer NCI‐H460 cells. 相似文献
33.
Valorization of waste thermoset material as a filler in thermoplastic: Mechanical properties of phenolic molding compound waste‐filled PP composites 下载免费PDF全文
Fabien Bernardeau Didier Perrin Anne‐Sophie Caro Jean‐Charles Benezet Patrick Ienny 《应用聚合物科学杂志》2018,135(12)
As most thermoset material, phenolic molding compound (PMC) wastes are an environmental problem. Very few recycling solutions have been proposed so far for this type of material. A mechanical recycling method to valorize these materials is proposed in this work. It relies on the use of phenolic waste as filler in thermoplastic. Such phenolic filler can increase mechanical properties (tensile, flexural) of the matrix, and be used in substitution of traditional particulate fillers such as calcium carbonate or talc. In this study, several morphological parameters influencing the final mechanical properties of a PMC‐filled polypropylene (PP) micro‐composite are studied, such as filler loading rate, particles size distribution of the filler, and interfacial adhesion between the filler and the matrix. Some structural parameters are also studied and linked with mechanical properties, such as dispersion of the filler and crystallinity of the matrix. Finally, the properties of PMC‐filled PP are compared with CaCO3‐ and talc‐filled PP. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 45849. 相似文献
34.
We report a method to improve the thermal stability, up to 900 °C, of bare-metal (naked) gold nanoparticles supported on top of SiO(2) and SrTiO(3) substrates via ligand-assisted pinning. This approach leads to monodisperse naked gold nanoparticles without significant sintering after thermal annealing in air at 900 °C. The ligand-assisted pinning mechanism is described. 相似文献
35.
High temperature tribological characterisation of TiAlSiN coatings produced by cathodic arc evaporation 总被引:2,自引:0,他引:2
Gonzalo G. Fuentes Eluxka Almandoz Rosario Martínez Jaume Caro 《Surface & coatings technology》2010,205(5):1368-1373
This study reports on the wear properties at medium-high temperatures of TiAlSiN films deposited by cathodic arc evaporation on hot work steel substrates. The chemical composition and microstructure of the coatings were characterised by glow discharge optical emission spectroscopy, scanning electron microscopy and X-ray diffraction. The mechanical properties, i.e. hardness and elastic modulus were evaluated by nanoindentation, and the adhesion of the coatings was tested by scratch tests. Coatings with stoichiometries of Ti0.31Al0.1Si0.06N0.53 and Ti0.23Al0.12Si0.09N0.55 exhibit microstructures consisting of solid solutions of (Ti,Al,Si)N, where Al and Si replace Ti atoms. These films show high hardness and good adhesion strength to the hot work steels. Conversely, coatings with a stoichiometry of Ti0.09Al0.34Si0.02N0.55 show a wurtzite-like microstructure, low hardness and poor adhesion strength.The wear rates of the coatings were investigated by ball-on-disc experiments at room temperature, 200 °C, 400 °C and 600 °C, using alumina balls as counter surfaces. At room temperature, the films show wear rates of the same order of magnitude of TiN and TiAlN coatings. On the other hand, the wear rates of solid solution (Ti,Al,Si)N coatings measured at 200, and 400 °C are one order of magnitude smaller than those measured at room temperature due to the formation of oxide-containing tribofilms on the wear tracks. At 600 °C the wear rates increase but still keep smaller than those measured at room temperature, although this effect can be influenced by the softening of the steel substrates by over-tempering. EDS analyses revealed that, between 200 °C and 400 °C, the oxidation of the coating occurs only at the contact zone between the film and the counterpart body due to the sliding process. 相似文献
36.
Fitó M Covas MI Lamuela-Raventós RM Vila J Torrents L de la Torre C Marrugat J 《Lipids》2000,35(6):633-638
The protective effect of phenolic compounds from an olive oil extract, and of olive oils with (extra-virgin) and without (refined)
phenolic components, on low density lipoprotein (LDL) oxidation was investigated. When added to isolated LDL, phenolics [0.025–0.3
mg/L caffeic acid equivalents (CAE)] increased the lag time of conjugated diene formation after copper-mediated LDL oxidation
in a concentration-dependent manner. Concentrations of phenolics greater than 20 mg/L inhibited formation of thiobarbituric-acid
reactive substances after AAPH-initiated LDL oxidation. LDL isolated from plasma after preincubation with phenolics (25–160
mg/L CAE) showed a concentration-dependent increase in the lag time of conjugated diene formation after copper-mediated LDL
oxidation. Refined olive oil (0 mg/L CAE) and extra-virgin olive oil (0.1 and 0.3 mg/L CAE) added to isolated LDL caused an
increase in the lag time of conjugated diene formation after copper-mediated LDL oxidation that was related to olive oil phenolic
content. Multiple regression analysis showed that phenolics were significantly associated with the increase in lag time after
adjustment for effects of other antioxidants; α-tocopherol also achieved a statistically significant effect. These results
indicate that olive oil phenolic compounds protect LDL against peroxyl radical-dependent and metal-induced oxidation in vitro and could associate with LDL after their incubation with plasma. Both types of olive oil protect LDL from oxidation. Olive
oil containing phenolics, however, shows more antioxidant effect on LDL oxidation than refined olive oil. 相似文献
37.
Yanis Caro Pierre Villeneuve Michel Pina Max Reynes Jean Graille 《Journal of the American Oil Chemists' Society》2000,77(8):891-902
The protein contents in crude latices from various varieties of papaya (Carica papaya) and their catalytic activities in proteolysis, lipolysis, and interesterification reactions were studied with regard to
the variety, the geographic location of cultures, and the frequency of fruit tapping. Biocatalytic activities of these raw
materials were compared to several commercially available crude and purified preparations of papain. These investigations
were carried out in order to have a better physicochemical characterization of these raw materials, to select the adequate
papaya latex for protein or lipid bioconversions, and to valorize them on an industrial scale. For the purified preparations
of papain, only proteolytic activity was obtained. All crude papaya latices exhibit proteolytic, lipolytic, and interesterification
activities, and no relationship between the proteolytic and lipolytic activities was observed. The high multiple correlation
coefficient (R) on the order of R=0.93–0.99, obtained from the regression analysis for the lipolytic and interesterification activities for all crude papaya
latices investigated suggested that there was a correlation between these enzyme activities. However, for the same lipase
preparation, the interesterification activity differed substantially depending on the type of interesterification reaction. 相似文献
38.
39.
Oliver Czuprat Steffen Werth Jürgen Caro Thomas Schiestel 《American Institute of Chemical Engineers》2010,56(9):2390-2396
A membrane reactor incorporating a hollow fiber with successive parts of oxygen permeable and passivated surface segments has been developed and was used for the oxidative dehydrogenation (DH) of propane. This membrane geometry allows a controlled oxygen feeding into the reactor over its axial length. In the oxidative DH, the thermodynamic limitation of propane DH can be overcome. By using this novel hollow fiber membrane reactor with a Pt/Sn/K DH catalyst, oxygen separation and propene formation could be established even at temperatures as low as 625°C with long‐term stability. Combining the hollow fiber membrane and the DH catalyst, the highest propene selectivity of 75% was observed at a propane conversion of 26% and 625°C whereas the best propene yield of 36% was obtained at 675°C (48% propene selectivity). The performance of this reactor is evaluated by applying various reaction conditions. © 2010 American Institute of Chemical Engineers AIChE J, 2010 相似文献
40.
Dr. Elena Petit Dr. Lluís Bosch Prof. Anna M. Costa Ignacio Rodríguez-Izquierdo Dr. Daniel Sepúlveda-Crespo Prof. M. Angeles Muñoz-Fernández Prof. Jaume Vilarrasa 《ChemMedChem》2021,16(14):2217-2222
Amides from indole-3-glyoxylic acid and 4-benzoyl-2-methylpiperazine, which are related to entry inhibitors developed by Bristol-Myers Squibb (BMS), have been synthesized with aliphatic chains located at the C7 position of the indole ring. These spacers contain an azido group suitable for the well-known Cu(I)-catalyzed (3+2)-cycloaddition or an activated triple bond for the nucleophilic addition of thiols under physiological conditions. Reaction with polyols (β-cyclodextrin and hyperbranched polyglycerol) decorated with complementary click partners has afforded polyol-BMS-like conjugates that are not cytotoxic (TZM.bl cells) and retain the activity against R5-HIV-1NLAD8 isolates. Thus, potential vaginal microbicides based on entry inhibitors, which can be called of 4th generation, are reported here for the first time. 相似文献