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排序方式: 共有1415条查询结果,搜索用时 78 毫秒
1.
Dr. Eduarda Mendes Enrico Cadoni Filipa Carneiro Dr. Marta B. Afonso Hugo Brito Dr. João Lavrado Dr. Daniel J. V. A. dos Santos Dr. Jorge B. Vítor Prof. Stephen Neidle Prof. Cecília M. P. Rodrigues Prof. Alexandra Paulo 《ChemMedChem》2019,14(14):1325-1328
Quadruplex nucleic acids are promising targets for cancer therapy. In this study we used a fragment-based approach to create new flexible G-quadruplex (G4) DNA-interactive small molecules with good calculated oral drug-like properties, based on quinoline and triazole heterocycles. G4 melting temperature and polymerase chain reaction (PCR)-stop assays showed that two of these compounds are selective G4 ligands, as they were able to induce and stabilize G4s in a dose- and DNA sequence-dependent manner. Molecular docking studies have suggested plausible quadruplex binding to both the G-quartet and groove, with the quinoline module playing the major role. Compounds were screened for cytotoxicity against four cancer cell lines, where 4,4′-(4,4′-(1,3-phenylene)bis(1H-1,2,3-triazole-4,1-diyl))bis(1-methylquinolin-1-ium) ( 1 d ) showed the greater activity. Importantly, dose–response curves show that 1 d is cytotoxic in the human colon cancer HT-29 cell line enriched in cancer stem-like cells, a subpopulation of cells implicated in chemoresistance. Overall, this study identified a new small molecule as a promising lead for the development of drugs targeting G4 in cancer stem cells. 相似文献
2.
Miguel Pallares Davide Fascione Gianluca Iannotta Alessandro Laner Alessandro Leanti Enrico Pellegrini Jenny Spagnolatti Santiago Trujillo Anna Zauli Andrea Martiradonna 《世界建筑导报》2018,(5)
正Piuarch建筑师事务所负责设计了2015年米兰世博会埃内尔(意大利国家电力公司)展馆及卡里塔斯展馆。为了将客户想表达的含义与价值观更好地传达给观众,Piuarch选择了一种特殊的建筑语言来体现两个展馆的特点。埃内尔展馆沿东西大街而建,占地900平方米。设计体现出智能电网这一概念,传达出以智能科技优化世博会整体用电的理念。 相似文献
3.
Dr. Ivan A. Yaremenko Dr. Paolo Coghi Parichat Prommana Congling Qiu Peter S. Radulov Yuanqing Qu Yulia Yu. Belyakova Dr. Enrico Zanforlin Dr. Vladimir A. Kokorekin Yuki Yu Jun Wu Prof. Fabrice Fleury Dr. Chairat Uthaipibull Dr. Vincent Kam Wai Wong Prof. Alexander O. Terent'ev 《ChemMedChem》2020,15(13):1118-1127
This article discloses a new horizon for the application of peroxides in medical chemistry. Stable cyclic peroxides are demonstrated to have cytotoxic activity against cancer cells; in addition a mechanism of cytotoxic action is proposed. Synthetic bridged 1,2,4,5-tetraoxanes and ozonides were effective against HepG2 cancer cells and some ozonides selectively targeted liver cancer cells (the selectivity indexes for compounds 11 b and 12 a are 8 and 5, respectively). In some cases, tetraoxanes and ozonides were more selective than paclitaxel, artemisinin, and artesunic acid. Annexin V flow-cytometry analysis revealed that the active ozonides 22 a and 23 a induced cell death of HepG2 by apoptosis. Further study showed that compounds 22 a and 23 a exhibited a strong inhibitory effect on P-glycoprotein (P-gp/ABCB5)-overexpressing HepG2 cancer cells. ABCB5 is a key player in the multidrug-resistant phenotype of liver cancer. Peroxides failed to demonstrate a direct correlation between oxidative potential and their biological activity. To our knowledge this is the first time that peroxide diastereoisomers have been found to show stereospecific antimalarial action against the chloroquine-sensitive 3D7 strain of Plasmodium falciparum. Stereoisomeric ozonide 12 b is 11 times more active than stereoisomeric ozonide 12 a (IC50=5.81 vs 65.18 μm ). Current findings mean that ozonides merit further investigation as potential therapeutic agents for drug-resistant hepatocellular carcinoma. 相似文献
4.
Enrico Casella Marco Ortolani Simone Silvestri Sajal K. Das 《Personal and Ubiquitous Computing》2020,24(4):451-464
Recognizing users’ daily life activities without disrupting their lifestyle is a key functionality to enable a broad variety of advanced services for 相似文献
5.
Dr. Blijke S. Kroezen Gabriele Conti Benedetta Girardi Dr. Jonathan Cramer Dr. Xiaohua Jiang Dr. Said Rabbani Jennifer Müller Maja Kokot Enrico Luisoni Prof. Daniel Ricklin Dr. Oliver Schwardt Prof. Beat Ernst 《ChemMedChem》2020,15(18):1706-1719
Siglecs are members of the immunoglobulin gene family containing sialic acid binding N-terminal domains. Among them, Siglec-8 is expressed on various cell types of the immune system such as eosinophils, mast cells and weakly on basophils. Cross-linking of Siglec-8 with monoclonal antibodies triggers apoptosis in eosinophils and inhibits degranulation of mast cells, making Siglec-8 a promising target for the treatment of eosinophil- and mast cell-associated diseases such as asthma. The tetrasaccharide 6’-sulfo-sialyl Lewisx has been identified as a specific Siglec-8 ligand in glycan array screening. Here, we describe an extended study enlightening the pharmacophores of 6’-sulfo-sialyl Lewisx and the successful development of a high-affinity mimetic. Retaining the neuraminic acid core, the introduction of a carbocyclic mimetic of the Gal moiety and a sulfonamide substituent in the 9-position gave a 20-fold improved binding affinity. Finally, the residence time, which usually is the Achilles tendon of carbohydrate/lectin interactions, could be improved. 相似文献
6.
Enrico Kleebusch Christian Patzig Thomas Höche Christian Rüssel 《Ceramics International》2018,44(16):19818-19824
Glass-ceramics based on lithium-alumo-silicate glasses are commercially important for a wide range of applications, due to their special properties, like a vanishing thermal expansion. In order to tailor these properties, the composition of the glass and the temperature/time schedule are crucial factors. For the industrial production of most lithium-alumo-silicate glasses, high melting temperatures are required due to the high viscosities of the respective melt compositions. In this study, a simplified lithium-alumo-silicate glass composition with ZrO2 as nucleating agent, on the basis of the commercially available Robax® composition, is studied. Adding boron oxide leads to lower viscosities of the glass melt and notably lower melting temperatures may be supplied. The resulting glass is investigated using X-ray diffraction and transmission electron microscopy. During the crystallization process, phases such as ZrO2 and β-quartz types are formed. The microstructure of the glass ceramics is notably coarser than that of glass-ceramics which are obtained from lithium-alumo-silicate glasses of standard compositions. EDX-analyses indicate a considerable enrichment of chemical elements in comparatively small areas of the microstructure. Especially boron oxide is found to be enriched in the residual glass of the investigated glass-ceramics. 相似文献
7.
Anna Enrico Wenjing Zhang Marie Lund Traulsen Elena Marzia Sala Paola Costamagna Peter Holtappels 《Journal of the European Ceramic Society》2018,38(7):2677-2686
Water-based sol-gel electrospinning is employed to manufacture perovskite oxide La0.6Sr0.4Co0.2Fe0.8O3-δ (LSCF) nanofiber cathodes for intermediate-temperature solid oxide fuel cells. LSCF fibrous scaffolds are synthesized through electrospinning of a sol-gel solution employing water as the only solvent. Morphological characterizations demonstrate that the LSCF fibers have highly crystalline structure with uniform elemental distribution. After heat treatment, the average fiber diameter is 250 nm and the porosity of the nanofiber tissue is 37.5 %. The heat treated LSCF nanofibers are applied directly onto a Ce0.9Gd0.1O1.95 (CGO) electrolyte disk to form a symmetrical cell. Electrochemical characterization is carried out through electrochemical impedance spectroscopy (EIS) in the temperature range 550?°C–950?°C, and reproducibility of the electrochemical performance for a series of cells is demonstrated. At 650?°C, the average measured polarization resistance Rp is 1.0 Ω cm2. Measured performance decay is 1 % during the first 33?h of operation at 750?°C, followed by an additional 0.7 % over the subsequent 70?h. 相似文献
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