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The separation and quantitation of coumarinic anticoagulant drug enantiomers were achieved by direct chiral capillary electrophoresis using complex maltooligosaccharide mixtures as stereoselective electrolyte modifiers. Chiral separations were characterized by a high selectivity and efficiency, enabling enantiomeric excess determinations. In addition, preliminary results indicate the applicability of the method for the determination of individual enantiomers in biological samples. So the method can be used to perform stereoselective pharmacokinetic studies. © 1994 Wiley-Liss, Inc. 相似文献
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BackgroundSchiff base metal complexes are considered promising chemotherapeutic agents due to their potential application in cancer therapy.MethodsThe current work sought to synthesize a brand-new Schiff base ligand obtained from 2-hydroxybenzohydrazide and (E)− 1-(2-(p-tolyl)hydrazono)propan-2-one with metal ions which included Pd(II) and Zn(II) ions. Elemental analyses, FT-IR, mass spectra, 1H NMR, UV-Vis spectrometer, and computational analysis characterized the compound's structure. In vitro, the breast cancer cell line (MCF-7) was tested for its sensitivity to Schiff base (HL) and its Pd(II) and Zn(II) complexes. The half-maximal inhibitory concentration IC50 of the compounds was determined and used to perform the comet assay, which was carried out to reveal the photo-induced DNA damaging ability of the compounds of individual cells. Moreover, the compounds' effects on antioxidant defense systems of enzymes in cells: superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities and oxidant Malondialdehyde (MDA) were examined in MCF-7 cells.ResultsThe Pd(II) complex displayed approximately the same IC50 as Cisplatin, while Zn(II) complex had better activity than Cisplatin with very low IC50, 1.40 μg/ml. Significant alterations in SOD, CAT, GPx, and MDA production were discovered, inducing oxidative stress, enlarging ROS production, and reducing the antioxidant amount. This change was approximately similar in most compounds. Consequently, it promoted apoptosis, particularly the Zn(II) complex, which demonstrated an improved impact because of its ability to influence the antioxidant defense systems of enzymes, mostly SOD and GPx, besides increasing MDA levels.ConclusionIt can be concluded that Zn(II) complex is the most effective anticancer drug since it induced a very similar genotoxic effect as Cisplatin and has a very low IC50 value. 相似文献
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Hannah Maus Gerald Hinze Stefan Josef Hammerschmidt Thomas Basché Tanja Schirmeister 《Protein science : a publication of the Protein Society》2023,32(1):e4526
Ligand binding to proteins often is accompanied by conformational transitions. Here, we describe a competition assay based on single molecule Förster resonance energy transfer (smFRET) to investigate the ligand-induced conformational changes of the dengue virus (DENV) NS2B-NS3 protease, which can adopt at least two different conformations. First, a competitive ligand was used to stabilize the closed conformation of the protease. Subsequent addition of the allosteric inhibitor reduced the fraction of the closed conformation and simultaneously increased the fraction of the open conformation, demonstrating that the allosteric inhibitor stabilizes the open conformation. In addition, the proportions of open and closed conformations at different concentrations of the allosteric inhibitor were used to determine its binding affinity to the protease. The KD value observed is in accordance with the IC50 determined in the fluorometric assay. Our novel approach appears to be a valuable tool to study conformational transitions of other proteases and enzymes. 相似文献
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Effects of in vivo exposure with fenvalerate, esfenvalerate andDDT on hepatic gap junctional intercellular communication (GJIC) in Sprague-Dawley (SD) rats were examined by in vivolin vitro dye-transfer assay and by immunohistochemical staining of connexin 32 (C×32, major liver gap junction protein). Fenvalerate (75 mg/kg/day), esfenvalerate (25 mg/kg/day), DDT (50 mg/kg/day) and corn oil (vehicle control, 5mllkglday) were administered orally once a day. Animals were killed at weeks 1, 2, 4 and 6 after starting the experiment. In the fenvalerate- and esfenvalerate-groups, no compound-related changes in GJIC and C×32 expression were observed. On the contrary, in the DDT-group, average sizes of the dye spread after injection of Lucifer Yellow decreased at weeks 1, 2 and 4, and the area per GJ spot shown by C×32-immunohistochemical staining decreased at weeks 4 and 6. It is concluded that neither fenvalerate nor esfenvalerate inhibits hepatic GJIC with in vivo exposure. 相似文献
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《Journal of molecular biology》2023,435(13):168129
Mitochondrial protein import is critical for organelle biogenesis, bioenergetic function, and health. The mechanism of which is poorly understood, particularly of the mammalian system. To address this problem we have established an assay to quantitatively monitor mitochondrial import inside mammalian cells. The reporter is based on a split luciferase, whereby the large fragment is segregated in the mitochondrial matrix and the small complementary fragment is fused to the C-terminus of a purified recombinant precursor protein destined for import. Following import the complementary fragments combine to form an active luciferase–providing a sensitive, accurate and continuous measure of protein import. This advance allows detailed mechanistic examination of the transport process in live cells, including the analysis of import breakdown associated with disease, and high-throughput drug screening. Furthermore, the set-up has the potential to be adapted for the analysis of alternative protein transport systems within different cell types, and multicellular model organisms. 相似文献