A5054788356- Pharmacogenetics and Drug Metabolism
- Drug Transport and Resistance Mechanisms
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Analytical Chemistry and Chromatography
- Chemical Reactions and Isotopes
- Gut microbiota and health
- Cancer Treatment and Pharmacology
- Computational Drug Discovery Methods
- Drug-Induced Hepatotoxicity and Protection
- Porphyrin and Phthalocyanine Chemistry
- Molecular Sensors and Ion Detection
- Eicosanoids and Hypertension Pharmacology
- Diet and metabolism studies
- Metabolomics and Mass Spectrometry Studies
- Luminescence and Fluorescent Materials
- Hormonal Regulation and Hypertension
- Free Radicals and Antioxidants
- Pharmacological Effects and Toxicity Studies
- Analytical Chemistry and Sensors
- Mass Spectrometry Techniques and Applications
- Metabolism and Genetic Disorders
- Silymarin and Mushroom Poisoning
- Genomics, phytochemicals, and oxidative stress
- Hemoglobin structure and function
Palacký University Olomouc
2015-2024
Institute of Molecular and Translational Medicine
2014-2023
University Hospital Olomouc
2016-2019
Institute of Pharmacology
2003-2016
Washington State University
2016
Regional Centre of Advanced Technologies and Materials
2012-2016
Ninewells Hospital
2016
University of Dundee
2016
University of Kansas
2016
Louisiana State University Health Sciences Center New Orleans
2016
A new Ru(II) complex is described which serves as a luminescence lifetime-based sensor for fluoride and cyanide anions (KF = 640 000 mol-1, KCN 430 mol-1). This chromophore displays observable changes in its UV−vis steady-state spectra upon binding. Prior to addition, this exhibits single-exponential lifetime (τ 377 ± 20 ns). With increasing concentrations, the intensity decays are composed of two exponentials: long τ (320−370 ns) short (13−17 The average lifetimes shorten function...
The use of the 3,4-difluoro-1H-pyrrole as a building block for preparation octamethyloctafluorocalix[4]pyrrole and 2,3-di(3',4'-difluoropyrrol-2'yl)quinoxaline is described. These latter two entities act neutral anion receptors were found to bind anions such fluoride, chloride, or dihydrogen phosphate with an enhanced affinity compared their non-fluorinated congeners judged from 1H NMR, 19F fluorescence emission spectroscopic analyses. increase in was especially high case chloride anion,...
Reliable sensing of structurally similar anions in water is a difficult problem, and analytical tests sensor devices for reliable multiple are very rare. This study describes method fabrication simple colorimetric array-based assays aqueous anion solutions, including complex analytes encountered real-life applications. On the fundamental level, this shows how discriminatory capacity arrays utilizing pattern recognition operating multianalyte environments may be dramatically improved by...
In our study, we tested the hypothesis whether valproic acid (VPA) in therapeutic concentrations has potential to affect expression of CYP3A4 and MDR1 via constitutive androstane receptor (CAR) pregnane X (PXR) pathways. Interaction VPA with CAR PXR nuclear receptors was studied using luciferase reporter assays, real-time reverse transcriptase polymerase chain reaction (RT-PCR), electrophoretic mobility shift assay (EMSA), analysis catalytic activity. Using transient transfection assays...
Cytochrome P450 2C9 (CYP2C9) is a membrane-anchored human microsomal protein involved in the drug metabolism liver. CYP2C9 consists of an N-terminal transmembrane anchor and catalytic cytoplasmic domain. While structure domain well-known from X-ray experiments, complete its incorporation into membrane remains unsolved. We constructed atomistic model dioleoylphosphatidylcholine evolved it by molecular dynamics simulations explicit water on 100+ ns time-scale. The agrees well with known...
Human cytochromes P450 (CYPs) are membrane-anchored enzymes involved in biotransformation of many marketed drugs. We constructed atomic models six human CYPs (CYP1A2, 2A6, 2C9, 2D6, 2E1, and 3A4) anchored to a lipid bilayer investigate the positions orientations on membrane. equilibrated by molecular dynamics simulations 100+ ns time scale. Catalytic domains all studied were found be partially immersed bilayer, whereas N-terminal part F'/G' loop deeply immersed. The proximal side enzyme...
Silybin and related flavonolignans form a major part of the Silybum marianum extract, silymarin, which has been used to treat liver diseases for hundreds years. Although regarded as safe, many extract constituents remain thus far untested their possible effects on biotransformation enzymes. Cytochromes P450 (CYP) are very important in this regard. We tested effect four flavonolignans: silybin, its hemisynthetic derivative dehydrosilybin, silydianin, silycristin three specific CYP activities:...
Molecular dynamics (MD) simulations at normal and high temperature were used to study the flexibility malleability of three microsomal cytochromes P450 (CYPs): CYP3A4, CYP2C9, CYP2A6. Comparison B-factors (describing atomic fluctuations) between X-ray MD data shows that are significantly lower in regions where crystal contacts occur than for other regions. Consequently, conclusions about CYP based solely on might be misleading. patterns CYPs enabled common features variations studied...
The growing interest in the composition and effects of microbiota raised question how drug pharmacokinetics could be influenced by concomitant application probiotics. aim this study was to find whether probiotic E. coli strain Nissle 1917 (EcN) influences concomitantly taken antiarrhythmic amiodarone (AMI). Live bacterial suspension EcN (or non-probiotic ATCC 25922) applied orally male Wistar rats for seven days, while a control group treated with saline solution. On eighth day,...
5,8-Diaryl-2,3-dipyrrolylquinoxaline materials display anion-induced changes in color and fluorescence quenching, thus acting as potential sensors for inorganic anions with affinity fluoride dihydrogenpyrophosphate. Such polyurethane matrix allow colorimetric screening of aqueous anion solutions.
We investigated cytochrome P450 (P450)-catalyzed metabolism of the important cancer drugs paclitaxel and docetaxel in rat, pig, minipig, human liver microsomes cDNA-expressed enzymes. In rat microsomes, was metabolized mainly to C3′-hydroxypaclitaxel (C3′-OHP) a lesser extent C2-hydroxypaclitaxel (C2-OHP), di-hydroxypaclitaxel (di-OHP), another unknown monohydroxylated paclitaxel. pig minipig this hydroxypaclitaxel main metabolite, whereas C3′-OHP minor product. minipigs, C2-OHP next...
ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTDirect Synthesis of Expanded Fluorinated Calix[n]pyrroles: Decafluorocalix[5]pyrrole and Hexadecafluorocalix[8]pyrroleJonathan L. Sessler, , James A. Shriver, Karolina Jursíková, Vincent M. Lynch, Manuel MarquezView Author Information Department Chemistry Biochemistry Institute for Cellular Molecular Biology University Texas at Austin, 78712-1167 Cite this: J. Am. Chem. Soc. 2000, 122, 48, 12061–12062Publication Date (Web):November 15,...