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71.
72.
Rebecca Vande Voorde Elizaveta Dzalamidze Dylan Nelson Lia Danelishvili 《Molecules (Basel, Switzerland)》2022,27(18)
Mycobacterial pathogens are intrinsically resistant to many available antibiotics, making treatment extremely challenging, especially in immunocompromised individuals and patients with underlying and chronic lung conditions. Even with lengthy therapy and the use of a combination of antibiotics, clinical success for non-tuberculous mycobacteria (NTM) is achieved in fewer than half of the cases. The need for novel antibiotics that are effective against NTM is urgent. To identify such new compounds, a whole cell high-throughput screen (HTS) was performed in this study. Compounds from the Chembridge DIVERSet library were tested for their ability to inhibit intracellular survival of M. avium subsp. hominissuis (MAH) expressing dtTomato protein, using fluorescence as a readout. Fifty-eight compounds were identified to significantly inhibit fluorescent readings of MAH. In subsequent assays, it was found that treatment of MAH-infected THP-1 macrophages with 27 of 58 hit compounds led to a significant reduction in intracellular viable bacteria, while 19 compounds decreased M. abscessus subsp. abscessus (Mab) survival rates within phagocytic cells. In addition, the hit compounds were tested in M. tuberculosis H37Ra (Mtb) and 14 compounds were found to exhibit activity in activated THP-1 cells. While the majority of compounds displayed inhibitory activity against both replicating (extracellular) and non-replicating (intracellular) forms of bacteria, a set of compounds appeared to be effective exclusively against intracellular bacteria. The efficacy of these compounds was examined in combination with current antibiotics and survival of both NTM and Mtb were evaluated within phagocytic cells. In time-kill dynamic studies, it was found that co-treatment promoted increased bacterial clearance when compared with the antibiotic or compound group alone. This study describes promising anti-NTM and anti-Mtb compounds with potential novel mechanisms of action that target intracellular bacteria in activated macrophages. 相似文献
73.
Matthew P. Stevens Emily Spray Iigo J. Vitorica-Yrezabal Kuldip Singh Vanessa M. Timmermann Lia Sotorrios Fabrizio Ortu 《Molecules (Basel, Switzerland)》2022,27(14)
Herein, we report the synthesis of a series of heteroleptic magnesium complexes stabilized with the scorpionate ligand tris(2-pyridylthio)methanide (Tptm). The compounds of the general formula [Mg(Tptm)(X)] (1-X; X = Cl, Br, I) were obtained via protonolysis reaction between the proligand and selected Grignard reagents. Attempts to isolate the potassium derivative K(Tptm) lead to decomposition of Tptm and formation of the alkene (C5H4N-S)2C=C(C5H4N-S)2, and this degradation was also modelled using DFT methods. Compound 1-I was treated with K(CH2Ph), affording the degradation product [Mg(Bptm)2] (2; Bptm = {CH(S-C5NH3)2}−). We analyzed and quantified the steric properties of the Tptm ligand using the structural information of the compounds obtained in this study paired with buried volume calculations, also adding the structural data of HTptm and its CF3-substituted congener (HTptmCF3). These studies highlight the highly flexible nature of this ligand scaffold and its ability to stabilize various coordination motifs and geometries, which is a highly desirable feature in the design of novel organometallic reagents and catalysts. 相似文献
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The commercially available diphosphane ligand MeO-BIPHEP was first investigated in the palladium-catalyzed Sonogashira reaction in the absence of copper and amine.The coupling of various aryl bromides and aryl chlorides with phenylacetylene gave moderate to excellent yields. 相似文献
77.
Mb2O5 -carbon nanocomposite is synthesized through a facile one-step hydrothermal reaction from sucrose as the carbon source,and studied as an anode material for high-performance lithium ion battery.The structural characterizations reveal that the nanocomposite possesses a core-shell structure with a thin layer of carbon shell homogeneously coated on the Nb2O5 nanocrystals.Such a unique structure enables the composite electrode with a long cycle life by preventing the Nb2O5 from volume change and pulverization during the charge-discharge process. In addition,the carbon shell efficiently improves the rate capability.Even at a current density of 500 mA·g-1,the composite electrode still exhibits a specific capacity of~100 mAh·g-1.These results suggest the possibility to utilize the Nb2O5-carbon core-shell composite as a high performance anode material in the practical application of lithium ion battery. 相似文献
78.
Tsuneaki Maeda 《中国化学快报》2010,21(6):730-733
<正>Triacontyl modified silica gel as a sorbent coupled with gas chromatography-mass spectrometry(GC-MS) was developed to determine EPA prior 16 polycyclic aromatic hydrocarbons(PAHs) in water samples.Various parameters of solid-phase extraction such as organic modifier solvent,eluent,sample flow rate and volume were optimized.The developed method was found to yield a linear calibration curve in the concentration range of 0.05-8μg/L with respect to naphthalene,acenaphthylene,acenaphthene and 0.01-8μg/L for dibenz[a,h]anthracene and 0.05-14μg/L for fluorene,phenanthrene,anthracene and 0.01-14μg/L for the rest of analytes.Furthermore,the good accuracy and repeatability of the method made sure the requirements for achieving reliable analysis of PAHs in the environmental water samples,and the recoveries of optimal method were in the range of 80-120%except to higher volatility PAHs.C_(30)-bonded silica was proved to be an efficient sorbent for extraction of high molecular weight PAHs. 相似文献
79.
The giant polyelectrolyte glycosaminoglycan hyaluronan (1-10 MDa) is a major component of the pericellular coat on a variety of cells, where it is an important modulator and mediator of early cell adhesion events. This pericellular layer can reach 5 mum thickness on cells that produce cartilage (chondrocytes), and up to 2 mum on Xenopus laevis kidney epithelial cells (A6). We are interested in generating model systems for the pericellular coat in order to learn more about the structure and function of hyaluronan on biological or artificial surfaces. We report here the synthesis of model systems where a coat of coordinatively cross-linked hyaluronan of up to 2 mum thickness was covalently photografted onto polystyrene microspheres. The hydrated coat was imaged directly by environmental scanning electron microscopy (ESEM) at close to 100% relative humidity. The key feature of the procedure is the reversible reverse-temperature phase transition of hyaluronan induced by trivalent lanthanide cations, which is exploited to achieve sufficient density for grafting of thick layers. The microsphere-grafted coat shows a temperature-dependent swelling when labeled with lanthanide ions (Gd(3+) or Tb(3+)). We directly observed a volume contraction of 20% with increasing temperature between 1 and 11 degrees C by wet-mode ESEM. 相似文献
80.
Ying Lu Yu Xian Li Chang Qiang Ke Chun Ping Tang Xin Zhou Yang Xi Qiang Li Yang Ye 《中国化学快报》2010,21(6):709-711
<正>A new iridoid glucoside,allamanoid(1),was isolated from the aerial parts of Allamanda neriifolia,together with three known glucosides,plumieride,protoplumericin,and nicotiflorin.Their structures were elucidated by 1D and 2D spectroscopic analyses, hydrolysis,and comparison with literature data. 相似文献