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Václav Bolemír Nebeský as a translator of Ancient literature
VEJVODOVÁ, Lucie
This bachelor´s thesis: "Václav Bolemír Nebeský as a translator of Ancient literature," deals with the Czech poet of the 19th century, Václav Bolemír Nebeský and especially with his translations from ancient literature. Above all, this work reveals his relationship to antiquity as to a certain period of history and his motivation to translate ancient authors. This thesis also works with the original sources from which Václav Bolemír Nebeský could draw upon and presents their final importance in the final translations. Last but least, this thesis also focuses on the theory of translation, the history of translation practices and compares the translation techniques of the past with the current ones. As a result, this bachelor´s thesis presents a comprehensive picture of Václav Bolemír Nebeský as an important translator of antiquity, explains his inner motivation for the translation of ancient literature and stresses the importance of his works as a part of the Czech literary canon of the 19th century.
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Study of mechanism of action of anticancer drug ellipticine and its metabolism
Vejvodová, Lucie ; Stiborová, Marie (advisor) ; Moserová, Michaela (referee)
This bachelor thesis is aimed to study the mechanisms of action of anticancer drugs, their side effects, their resistance and pharmacokinetics. Anticancer alkaloid ellipticine was chosen as a model for this work. Bachelor thesis describes the metabolism of this substance in organisms and its potential to induce of drug metabolizing enzymes. An antineoplastic alkaloid ellipticine is a prodrug, whose mode of action is based mainly on DNA intercalation, inhibition of topoisomerasa II, and formation of covalent DNA adducts mediated by cytochromes P450 and/or peroxidases in target tissues. A variety cytochromes P450 oxidize ellipticine forming up to five metabolites (7-hydroxyellipticine, 9- hydroxyellipticine, 12-hydroxyellipticine, 13-hydroxyellipticine and ellipticine N2 - oxide). 7- hydroxy- and 9-hydroxyellipticine metabolites are considered to be mainly the detoxication products of ellipticine, while 12-hydroxyellipticine, 13-hydroxyellipticine and ellipticine N2 - oxide are considered to be mainly the activation products of ellipticine. The major ellipticine- derived DNA adducts are generated from these activation metabolites. These adducts were found in cancer cells in culture, such as human breast adenocarcinoma MCF-7 cells, neuroblastoma IMR-32, UKF-NB-3, and UKF-NB-4 cells and glioblastoma...
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Oxidation of ellipticine by human cytochromes P450 expressed in prokaryotic and eukaryotic systems
Vejvodová, Lucie ; Stiborová, Marie (advisor) ; Hýsková, Veronika (referee)
Ellipticine is an alkaloid with antitumor activity, whose mechanism of action is based on intercalation into DNA, inhibition of topoisomerase II and formation of covalent adducts with DNA, after its enzymatic activation by cytochromes P450 and/or peroxidases. Ellipticine is oxidized by cytochromes P450 to form up to five metabolites (7-hydroxy-, 9-hydroxy, 12- hydroxy-, 13-hydroxyellipticine and N2 -oxide ellipticine). 9-Hydroxy- and 7- hydroxyellipticine are considered to be detoxification metabolites, whereas 12-hydroxy-, 13- hydroxyellipticine and N2 -oxide of ellipticine are considered as activation metabolites, which are responsible for formation of covalent DNA adducts. The aim of this thesis was to examine the efficiency of human recombinant cytochromes P450 expressed in eukaryotic (SupersomesTM ) and two prokaryotic expression systems (Bactosomes) in oxidation of ellipticine. Cytochromes P450 expressed in prokaryotic systems differed in the amounts of "coexpressed" NADPH:CYP reductase. The resulting ellipticine metabolites were analyzed by HPLC. The results obtained in this thesis demonstrate that human cytochromes P450 2C9/2D6/2C19 expressed in prokaryotic or eukaryotic systems oxidize ellipticine to form up to four metabolites: 9-hydroxy-, 12-hydroxy-, 13-hydroxyellipticine and N2 -oxide...
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Oxidation of ellipticine by human cytochromes P450 expressed in prokaryotic and eukaryotic systems
Vejvodová, Lucie ; Stiborová, Marie (advisor) ; Hýsková, Veronika (referee)
Ellipticine is an alkaloid with antitumor activity, whose mechanism of action is based on intercalation into DNA, inhibition of topoisomerase II and formation of covalent adducts with DNA, after its enzymatic activation by cytochromes P450 and/or peroxidases. Ellipticine is oxidized by cytochromes P450 to form up to five metabolites (7-hydroxy-, 9-hydroxy, 12- hydroxy-, 13-hydroxyellipticine and N2 -oxide ellipticine). 9-Hydroxy- and 7- hydroxyellipticine are considered to be detoxification metabolites, whereas 12-hydroxy-, 13- hydroxyellipticine and N2 -oxide of ellipticine are considered as activation metabolites, which are responsible for formation of covalent DNA adducts. The aim of this thesis was to examine the efficiency of human recombinant cytochromes P450 expressed in eukaryotic (SupersomesTM ) and two prokaryotic expression systems (Bactosomes) in oxidation of ellipticine. Cytochromes P450 expressed in prokaryotic systems differed in the amounts of "coexpressed" NADPH:CYP reductase. The resulting ellipticine metabolites were analyzed by HPLC. The results obtained in this thesis demonstrate that human cytochromes P450 2C9/2D6/2C19 expressed in prokaryotic or eukaryotic systems oxidize ellipticine to form up to four metabolites: 9-hydroxy-, 12-hydroxy-, 13-hydroxyellipticine and N2 -oxide...
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Study of mechanism of action of anticancer drug ellipticine and its metabolism
Vejvodová, Lucie ; Stiborová, Marie (advisor) ; Moserová, Michaela (referee)
This bachelor thesis is aimed to study the mechanisms of action of anticancer drugs, their side effects, their resistance and pharmacokinetics. Anticancer alkaloid ellipticine was chosen as a model for this work. Bachelor thesis describes the metabolism of this substance in organisms and its potential to induce of drug metabolizing enzymes. An antineoplastic alkaloid ellipticine is a prodrug, whose mode of action is based mainly on DNA intercalation, inhibition of topoisomerasa II, and formation of covalent DNA adducts mediated by cytochromes P450 and/or peroxidases in target tissues. A variety cytochromes P450 oxidize ellipticine forming up to five metabolites (7-hydroxyellipticine, 9- hydroxyellipticine, 12-hydroxyellipticine, 13-hydroxyellipticine and ellipticine N2 - oxide). 7- hydroxy- and 9-hydroxyellipticine metabolites are considered to be mainly the detoxication products of ellipticine, while 12-hydroxyellipticine, 13-hydroxyellipticine and ellipticine N2 - oxide are considered to be mainly the activation products of ellipticine. The major ellipticine- derived DNA adducts are generated from these activation metabolites. These adducts were found in cancer cells in culture, such as human breast adenocarcinoma MCF-7 cells, neuroblastoma IMR-32, UKF-NB-3, and UKF-NB-4 cells and glioblastoma...
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