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Antioxidative effects of the analogues of nucleic acid components.
Procházková, Eliška
Reactive oxygen species (ROS) naturally occur in the organisms where they play e.g. signaling and antimicrobial roles. The imbalance between ROS production and removal results in the oxidative stress. This condition is largely considered as unfavourable leading to the oxidative damage of the biomolecules (lipids, proteins, nucleic acids). The oxidative stress accompanies a number of civilization diseases and may also arise as a consequence of pharmacotherapy (side effects of some drugs). Modulation of the oxidative stress with the use of antioxidants remains a subject of intense research. The analogs of nucleic acid components represent a structurally diverse class of compounds with important pharmacological potential. While their antiviral and cytostatic activities have been described in detail, information on their potential antioxidant activity is missing. The aim of this study was to identify the antioxidant activity in a series of 126 analogs of nucleotides, nucleosides and nucleobases and to describe structural motives responsible for this activity. Several methodological approaches have been used to reach the goal: 1) determination of the ability of the compounds to scavenge ABTS radical in vitro (TEAC), 2) the influence of the compounds on lipid peroxidation and 3) their ability to...
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Paradise Lost and Silmarillion:Rebellion and evil in literary myths by John Milton and J.R.R. Tolkien
Procházková, Eliška ; Charypar, Michal (advisor) ; Sládek, Miloš (referee)
There is no doubt that profesor John Ronald Reuel Tolkien, while he was creating the oldest myths of his literary world, published under the title Silmarillion, worked not only with the Nordic, Germanic or Celtic myths, but as a Catholic did not forget about the christian stories. His inspirational sources certainly included it's biggest conflict, the Lucifer's rebellion against God. He apparently knew the most famous depiction of this theme, an extensive epic poem by an english baroque writer John Milton. In this thesis I will focus on Tolkien's own mythology and the strongest influences that could have affected it. And I will compare the story and destiny of Tolkien's Melkor with those of Satan. The biblical one and also the one as depicted by John Milton in his work. Keywords Tolkien, Milton, Silmarillion, Paradise lost, evil, mythology
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Separation of rotamers of 5-nitrosopyrimidines by capillary electrophoresis
Štěpánová, Sille ; Procházková, Eliška ; Čechová, Lucie ; Žurek, Jiří ; Janeba, Zlatko ; Dračínský, Martin ; Kašička, Václav
A new capillary electrophoresis (CE) method was developed for the separation of a new type of stereoisomers - rotamers of polysubstituted 5-nitrosopyrimidine derivatives. Partial separation of some rotamers was obtained in sodium borate, pH 9.3, or in Tris-phosphate, pH 2.2, background electrolytes (BGEs) free of cyclodextrins (CDs). However, the best, baseline separations of the rotamers of 5-nitrosopyrimidines were achieved in sodium borate BGE, pH 9.3, containing 20 mg/mL beta-CD as stereoselector, or in Tris-phosphate BGE, pH 2.2, with carboxymethyl-beta-CD as stereoselector.
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The effect of flavonoids on selected biotransformation enzymes
Procházková, Eliška ; Szotáková, Barbora (advisor) ; Skálová, Lenka (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Eliška Procházková Supervisor: Prof. Ing. Barbora Szotáková, Ph.D. Title of diploma thesis: The effect of flavonoids on selected biotransformation enzymes In recent years, catechins which belong to flavonoids have been studied polyphenolic constituents of green tea. Especially their beneficial effects on the human health are mostly studied. The popularity of dietary supplements with high levels of flavonoids is growing and thus they can affect a wide range of biotransformation enzymes and also the metabolism of many drugs. The aim of this diploma thesis was to find out how the selected catechins - catechin (C), epicatechin (EC), epicatechin 3-gallate (ECG), epigallocatechin (EGC), epigallocatechin 3-gallate (EGCG) and the green tea extract - polyphenon 60 (P) influence the viability of the Caco-2 cells and the activity and expression of the selected biotransformation enzymes in these cells - cytochromes P450 (CYP) isoforms 1A1, 1A2, and 3A, aldehyde reductase (AKR1A1), aldo-keto reductase 1C (AKR1C), carbonyl reductase 1 (CBR1), UDP-glucuronosyltransferase (UGT), sulfotransferase (SULT) and glutathione S-transferase (GST). The viability tests (NRU test and MTT test) proved that catechins (EGC,...
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Struktura a vlastnosti modifikovaných složek nukleových kyselin
Procházková, Eliška ; Dračínský, Martin (advisor) ; Lyčka, Antonín (referee) ; Hrabal, Richard (referee)
Modified nucleic acid components (nucleotides, nucleosides, nucleobases) display a wide range of biological activities such as antiviral, cytostatic, antimicrobial or antioxidative. Many of them are successfully used in clinical practice, for instance as anti-HIV drugs or in hepatitis B treatment. The first precondition for understanding biological effects is to evaluate the chemical structure as well as the conformation of the studied compounds correctly. For this purpose, solution-state nuclear magnetic resonance (NMR) spectroscopy in combination with mass spectrometry is the most frequently used method. Not only the structure, but also physico- chemical properties can be investigated using NMR spectroscopy, for instance, conformational changes, tautomeric forms, protonation sites, acido-basic properties, non-covalent interactions, isotopic exchanges or interactions with biomolecules. Similarly to solutions, NMR spectroscopy can be employed in studies of nucleic acid components (NACs) in solid state. This technique found assertion after computational-chemistry methods development during the last decades. Different solid-state structures (polymorphic forms) or dynamics of these compounds can be established by solid-state NMR spectroscopy in combination with quantum-chemical calculations. In this...
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Antioxidative effects of the analogues of nucleic acid components.
Procházková, Eliška
Reactive oxygen species (ROS) naturally occur in the organisms where they play e.g. signaling and antimicrobial roles. The imbalance between ROS production and removal results in the oxidative stress. This condition is largely considered as unfavourable leading to the oxidative damage of the biomolecules (lipids, proteins, nucleic acids). The oxidative stress accompanies a number of civilization diseases and may also arise as a consequence of pharmacotherapy (side effects of some drugs). Modulation of the oxidative stress with the use of antioxidants remains a subject of intense research. The analogs of nucleic acid components represent a structurally diverse class of compounds with important pharmacological potential. While their antiviral and cytostatic activities have been described in detail, information on their potential antioxidant activity is missing. The aim of this study was to identify the antioxidant activity in a series of 126 analogs of nucleotides, nucleosides and nucleobases and to describe structural motives responsible for this activity. Several methodological approaches have been used to reach the goal: 1) determination of the ability of the compounds to scavenge ABTS radical in vitro (TEAC), 2) the influence of the compounds on lipid peroxidation and 3) their ability to...
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The effect of flavonoids on selected biotransformation enzymes
Procházková, Eliška ; Szotáková, Barbora (advisor) ; Svobodová, Hana (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Eliška Procházková Supervisor: Doc. Ing. Barbora Szotáková, Ph.D. Title of diploma thesis: The effect of flavonoids on selected biotransformation enzymes In recent years, catechins which belong to flavonoids have been studied polyphenolic constituents of green tea. Especially their beneficial effects on the human health are mostly studied. The popularity of dietary supplements with high levels of flavonoids is growing and thus they can affect a wide range of biotransformation enzymes and also the metabolism of many drugs. The aim of this diploma thesis was to find out how the selected catechins - catechin (C), epicatechin (EC), epicatechin-3-gallate (ECG), epigallocatechin (EGC), epigallocatechin-3-gallate (EGCG) and the green tea extract - polyphenon 60 (P) influence the viability of the Caco-2 cells and the activity and expression of the selected biotransformation enzymes in these cells - cytochromes P450 (CYP) isoforms 1A1, 1A2, and 3A, aldehydreductase (AKR1A1), aldo-ketoreductases 1C (AKR1C), carbonylreductase 1 (CBR1), UDP-glucuronosyltransferase (UGT), sulfotransferase (SULT) and glutathione S-transferase (GST). The viability tests (NRU test and MTT test) proved that catechins...
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Antioxidative effects of the analogues of nucleic acid components.
Procházková, Eliška ; Mertlíková Kaiserová, Helena (advisor) ; Zusková, Iva (referee)
Reactive oxygen species (ROS) naturally occur in the organisms where they play e.g. signaling and antimicrobial roles. The imbalance between ROS production and removal results in the oxidative stress. This condition is largely considered as unfavourable leading to the oxidative damage of the biomolecules (lipids, proteins, nucleic acids). The oxidative stress accompanies a number of civilization diseases and may also arise as a consequence of pharmacotherapy (side effects of some drugs). Modulation of the oxidative stress with the use of antioxidants remains a subject of intense research. The analogs of nucleic acid components represent a structurally diverse class of compounds with important pharmacological potential. While their antiviral and cytostatic activities have been described in detail, information on their potential antioxidant activity is missing. The aim of this study was to identify the antioxidant activity in a series of 126 analogs of nucleotides, nucleosides and nucleobases and to describe structural motives responsible for this activity. Several methodological approaches have been used to reach the goal: 1) determination of the ability of the compounds to scavenge ABTS radical in vitro (TEAC), 2) the influence of the compounds on lipid peroxidation and 3) their ability to...
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