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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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Novel conformationally locked nucleosides and nucleotides based on bicyclo[3.2.1]octane scaffold as a pseudosugar moiety
Šála, Michal ; Dejmek, Milan ; Procházková, Eliška ; Hřebabecký, Hubert ; Rybáček, Jiří ; Dračínský, Martin ; Novák, Pavel ; Rosenbergová, Šárka ; Fukal, J. ; Sychrovský, Vladimír ; Rosenberg, Ivan ; Nencka, Radim
A route to a series of novel carbocyclic nucleosides locked in North conformation with bicyclo[3.2.1]octane scaffold was developed. Prepared nucleosides served as a starting material for the synthesis of modified oligomers [d(GCATATCAC), r(GCAUAUCAC), and A9]. Biological effects of the prepared nucleosides as well as the hybridization properties of the appropriate duplexes were evaluated.
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Synthesis and biological properties of polysubstituted 5-nitrosopyrimidines
Janeba, Zlatko ; Čechová, Lucie ; Žurek, Jiří ; Procházková, Eliška ; Dračínský, Martin
2,4,6-Triamino-5-nitrosopyrimidines have been reported to contain a strong intramolecular hydrogen bond between the 5-nitroso and 4- or 6-amino groups, thus forming an additional pseudoring. Such analogues were speculated to be good mimics of fused bicyclic derivatives, e.g. purines. A series of novel polysubstituted 2-amino-5-nitrosopyrimidines, as potential structural mimics of modifi ed purine nucleos(t)ides well-known for their important biological properties, has been designed and synthesized. The physicochemical and biological properties of the prepared polysubstituted 2-amino-5-nitrosopyrimidines are being evaluated.
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Switchable intramolecular hydrogen bond in polysubstituted 5-nitrosopyrimidines
Procházková, Eliška ; Čechová, Lucie ; Žurek, Jiří ; Janeba, Zlatko ; Dračínský, Martin
The formation of strong intramolecular hydrogen bonds was observed in a series of 2-amino-5-nitrosopyrimidines with alkylamino and arylamino substituents in the positions 4 and 6. Mixtures of two rotamers differing in the orientation of the nitroso group were observed in the NMR spectra of the compounds where two distinct intramolecular hydrogen bonds could be formed. In several cases, we were able to isolate and characterize the two hydrogen bond isomers (two conformers) by column chromatography. The ratio of the two rotamers in equilibrium depends strongly on the character of the substituents in the positions 4 and 6 and can be finely tuned in a broad range of conformation ratios. The experimental results were supported by DFT calculations.
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