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排序方式: 共有177条查询结果,搜索用时 15 毫秒
81.
Simone Schierle Moritz Helmstädter Dr. Jurema Schmidt Markus Hartmann Maximiliane Horz Astrid Kaiser Lilia Weizel Dr. Pascal Heitel Dr. Anna Proschak Dr. Victor Hernandez-Olmos Prof. Dr. Ewgenij Proschak Dr. Daniel Merk 《ChemMedChem》2020,15(1):50-67
The nuclear farnesoid X receptor (FXR) and the enzyme soluble epoxide hydrolase (sEH) are validated molecular targets to treat metabolic disorders such as non-alcoholic steatohepatitis (NASH). Their simultaneous modulation in vivo has demonstrated a triad of anti-NASH effects and thus may generate synergistic efficacy. Here we report dual FXR activators/sEH inhibitors derived from the anti-asthma drug Zafirlukast. Systematic structural optimization of the scaffold has produced favorable dual potency on FXR and sEH while depleting the original cysteinyl leukotriene receptor antagonism of the lead drug. The resulting polypharmacological activity profile holds promise in the treatment of liver-related metabolic diseases. 相似文献
82.
Prof. Mikhail Krasavin Daniil Zhukovsky Igor Solovyev Darina Barkhatova Prof. Dmitry Dar'in Denia Frank Giada Martinelli Lilia Weizel Dr. Anna Proschak Marco Rotter Dr. Jan S. Kramer Steffen Brunst Prof. Thomas A. Wichelhaus Prof. Ewgenij Proschak 《ChemMedChem》2021,16(22):3410-3417
Diversity-oriented synthesis (DOS) is a rich source for novel lead structures in Medicinal Chemistry. In this study, we present a DOS-compatible method for synthesis of compounds bearing a free thiol moiety. The procedure relies on Rh(II)-catalyzed coupling of dithiols to diazo building blocks. The synthetized library was probed against metallo-β-lactamases (MBLs) NDM-1 and VIM-1. Biochemical and biological evaluation led to identification of novel potent MBL inhibitors with antibiotic adjuvant activity. 相似文献
83.
Manuel Hofer Stefan Adamsmaier Thomas S. van Zanten Lilia A. Chtcheglova Carlo Manzo Memed Duman Barbara Mayer Andreas Ebner Manuel Moertelmaier Gerald Kada Maria F. Garcia-Parajo Peter Hinterdorfer Ferry Kienberger 《Ultramicroscopy》2010
We demonstrate simultaneous transverse dynamic force microscopy and molecular recognition imaging using tuning forks as piezoelectric sensors. Tapered aluminum-coated glass fibers were chemically functionalized with biotin and anti-lysozyme molecules and attached to one of the prongs of a 32 kHz tuning fork. The lateral oscillation amplitude of the tuning fork was used as feedback signal for topographical imaging of avidin aggregates and lysozyme molecules on mica substrate. The phase difference between the excitation and detection signals of the tuning fork provided molecular recognition between avidin/biotin or lysozyme/anti-lysozyme. Aggregates of avidin and lysozyme molecules appeared as features with heights of 1–4 nm in the topographic images, consistent with single molecule atomic force microscopy imaging. Recognition events between avidin/biotin or lysozyme/anti-lysozyme were detected in the phase image at high signal-to-noise ratio with phase shifts of 1–2°. Because tapered glass fibers and shear-force microscopy based on tuning forks are commonly used for near-field scanning optical microscopy (NSOM), these results open the door to the exciting possibility of combining optical, topographic and biochemical recognition at the nanometer scale in a single measurement and in liquid conditions. 相似文献
84.
The average energy efficiency of microwave convective drying is strongly related to drying time and thus to drying kinetics. This study investigates the energy efficiency of materials with different material properties and drying rates. Four solid, porous materials (swede, potato, bread, and lightweight concrete) were dried under the same microwave convective drying conditions. Drying behaviour, temperature development, hygroscopicity, dielectric properties, and specific energy consumption were studied. Despite differences in kinetics and product properties, the specific energy consumption (MJ/kg evaporated water) was approximately the same for all materials at intermediate to high moisture contents. When drying was pursued into the hygroscopic region, however, the specific energy consumption increased. The results indicate that a relationship between microwave penetration depth and water activity of the materials may be found. Drying of the food materials was limited by burning either due to temperature runaway in the hygroscopic region or due to development of hot spots, possibly induced by material structure. 相似文献
85.
Normal prostate tissue contains high levels of citrate. In the presence of prostate cancer, the citrate level is diminished. In this paper we show that it is possible to use europium-oxytetracycline complex as a citrate fluorescent probe and consequently as a prostate cancer probe. We analyzed normal nude male mice urine and urine from nude male mice in which prostate cancer was induced by intraprostatic inoculation of DU145 cells. The urine samples were collected from the animals at the 7th, 14th, 21st, and 35th days after the surgery procedures. The intensity of europium emission at 615 nm in europium-oxytetracycline complex in the presence of citrate increases linearly. The citrate concentrations were determined from a calculated calibration curve. A concentration decrease in malignant prostate urine from the normal (PBS group) urine value from ~8.0 mM to ~2.4 mM (tumor group at 35th day) was found. The obtained results indicated that europium-oxytetracycline provides a significant biomarker for prostate cancer detection with a direct, accurate, noninvasive, and non-enzymatic method for measurement of citrate in biological fluids. 相似文献
86.
Marco Rito‐Palomares Lilia Nuez Daniel Amador 《Journal of chemical technology and biotechnology (Oxford, Oxfordshire : 1986)》2001,76(12):1273-1280
A novel process for the recovery of c‐phycocyanin from Spirulina maxima exploiting aqueous two‐phase systems (ATPS), ultrafiltration and precipitation was developed in order to reduce the number of unit operations and benefit from an increased yield of the protein product. The evaluation of system parameters such as PEG molecular mass, concentration of PEG as well as salt, system pH and volume ratio was carried out to determine under which conditions the c‐phycocyanin and contaminants concentrate to opposite phases. PEG1450–phosphate ATPS proved to be suitable for the recovery of c‐phycocyanin because the target protein concentrated in the top phase whilst the cell debris concentrated in the bottom phase. A two‐stage ATPS process with a phase volume ratio (Vr) equal to 0.3, PEG1450 7% (w/w), phosphate 20% (w/w) and system pH of 6.5 allowed c‐phycocyanin recovery with a purity of 2.4 (estimated as the relationship of the 620 nm to 280 nm absorbances). The use of ultrafiltration (with a 30 kDa membrane cut‐off) and precipitation (with ammonium sulfate) resulted in a recovery process that produced a protein purity of 3.8 ± 0.1 and an overall product yield of 29.5% (w/w). The results reported here demonstrated the practical implementation of ATPS for the design of a prototype recovery process as a first step for the commercial purification of c‐phycocyanin produced by Spirulina maxima. © 2001 Society of Chemical Industry 相似文献
87.
R. Lilia Centeno-Sánchez Derek J. Fray George Z. Chen 《Journal of Materials Science》2007,42(17):7494-7501
Reduction of porous titanium oxide precursors by the FFC-Cambridge process is reported in this paper. Porous TiO2 precursors were prepared by mixing the powder with different concentrations of graphite and polyethylene as fugitive agents
and sintered at 1,073 K. The maximum porosity achieved before the mixture saturation was approximately 75%. After the electro-deoxidation
by the FFC-Cambridge process, shrinkage of approximately 40% in volume and increase in porosity were observed, which might
be due to atomic rearrangement, change of density and subsequent grain growth during reduction. The potential applied (below
the decomposition potential of CaCl2) had a direct effect on the minimum level of oxygen achieved, which was approximately 3,000 ppm for 48 h at 3.00 V and the
same level at half the time (24 h) when increasing potential to 3.15 V. On the other hand, thin layers (300 μm thickness)
screen-printed on titanium foils showed shorter reduction time than that observed for thicker porous pellets. This led to
the conclusion that cathode geometry (porosity and thickness of the pellet) might have an effect on the rate of reduction
by increasing the surface area available and improving the mass diffusion of oxygen ions. 相似文献
88.
89.
A simple and robust "off-on" signaling genosensor platform with improved selectivity for single-nucleotide polymorphism (SNP) detection based on the electronic DNA hairpin molecular beacons has been developed. The DNA beacons were immobilized onto gold electrodes in their folded states through the alkanethiol linker at the 3'-end, while the 5'-end was labeled with a methylene blue (MB) redox probe. A typical "on-off" change of the electrochemical signal was observed upon hybridization of the 27-33 nucleotide (nt) long hairpin DNA to the target DNA, in agreement with all the hitherto published data. Truncation of the DNA hairpin beacons down to 20 nts provided improved genosensor selectivity for SNP and allowed switching of the electrochemical genosensor response from the on-off to the off-on mode. Switching was consistent with the variation in the mechanism of the electron transfer reaction between the electrode and the MB redox label, for the folded beacon being characteristic of the electrochemistry of adsorbed species, while for the "open" duplex structure being formally controlled by the diffusion of the redox label within the adsorbate layer. The relative current intensities of both processes were governed by the length of the formed DNA duplex, potential scan rate, and apparent diffusion coefficient of the redox species. The off-on genosensor design used for detection of a cancer biomarker TP53 gene sequence favored discrimination between the healthy and SNP-containing DNA sequences, which was particularly pronounced at short hybridization times. 相似文献
90.