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Enzymes metabolizing drugs
Škodová, Petra ; Stiborová, Marie (advisor) ; Kubíčková, Božena (referee)
Mixed function oxidase system (MFO) is one of the most effective systems of enzymes of the first phase of biotransformation of xenobiotics. Cytochromes P450 seem to be the most important part of the MFO system, which also contains other components such as NADPH:CYP reductase and membrane lipids. Cytochromes P450 function as a terminal oxidase of the mixed function oxidase (MFO) system. Many xenobiotics, including drugs, are the substrates of these enzymes. Endogenous substances can serve as the substrates of these enzymes as well. Peroxidases are a group of enzymes which are able to metabolize drugs. The function of cytochromes P450 can be substituted by peroxidases. Both groups of enzymes are able to potentiate the effect of the drugs by activating them or they form deactivated metabolites, which are excreted from the organism. The action of cytochromes P450 and peroxidases is shown on the metabolism of the drug ellipticine. Ellipticine has anticancer effects. The advantage of this drug is its low number of side-effects. The oxidation of ellipticine by cytochromes P450 and peroxidases leads to its metabolic activation or detoxification. Carbenium ions are generated by spontaneous cleavage of two active metabolites, 12-hydroxyellipticine and 13-hydroxyellipticine. Carbenium ions then form adducts...
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Preparation of derivatives of anticancer drug ellipticine and their oxidation by cytochromes P450
Škodová, Petra ; Stiborová, Marie (advisor) ; Smrček, Stanislav (referee)
Ellipticine is a plant alkaloid, which exhibits significant antitumor activity; therefore it was a center of interest since 60's of 20th century. There were a lot of ways published to obtain this anticancer drug. Ellipticine is actually a pro-drug, whose pharmacological efficiencies are dependent on the activation of two groups of enzymes, cytochrome P450 and peroxidases. The resulting effect of these groups of enzymes is either detoxification or activation of ellipticine metabolites. 13-Hydroxyellipticine and 12-hydroxyellipticine are products of activation reactions, which subsequently spontaneously cleave to carbenium ions, which in this form are bound to deoxyguanosine while generating DNA adducts. 13-Hydroxyellipticine may have potentially higher biological efficiencies than ellipticine, because it does not need enzymes for its activation and formation of DNA adducts. The aim of the diploma thesis was to synthesize this ellipticine derivative. 9- Nitroellipticin (another derivative of ellipticine) is an intermediate product of the 13- hydroxyellipticine synthesis. Results of this diploma thesis show that 9-nitroellipticine is oxidized by liver microsomal systems, which contain cytochromes P450, forming at least 4 metabolites. 9-Nitroellipticine shows similar behavior as ellipticine. Another...
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Assessment of changes in land tenure and land use in selected locality
ŠKODOVÁ, Petra
This diploma thesis called "Assessment of changes in land tenure and land use in selected locality" is divided into a theoretical and practical part. In the first part, there is written a literary research, introducing the issue of land tenure in the Czech Republic. In the research, there is a comprehensive overview of historical registers of land tenure, coupled with major historical events and milestones affecting land ownership. Particular attention is paid here to the stable cadastre, from which is the practical part of this work based. An integral part of the research is the analysis of current land use of the Czech Republic, with the factors influencing it. The second part is devoted to the cadastral territory of Roupov, where a complete analysis and comparison of historical and current land use is made, together with comparison of ownership relations and evaluation of their mutual analogy within the time span between periods. Here are presented own map outputs, tables and charts. At the end of the thesis, attention was focused on identification of possible causes, causing changes in land use and comparison of land ownership.
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Preparation of derivatives of anticancer drug ellipticine and their oxidation by cytochromes P450
Škodová, Petra ; Stiborová, Marie (advisor) ; Smrček, Stanislav (referee)
Ellipticine is a plant alkaloid, which exhibits significant antitumor activity; therefore it was a center of interest since 60's of 20th century. There were a lot of ways published to obtain this anticancer drug. Ellipticine is actually a pro-drug, whose pharmacological efficiencies are dependent on the activation of two groups of enzymes, cytochrome P450 and peroxidases. The resulting effect of these groups of enzymes is either detoxification or activation of ellipticine metabolites. 13-Hydroxyellipticine and 12-hydroxyellipticine are products of activation reactions, which subsequently spontaneously cleave to carbenium ions, which in this form are bound to deoxyguanosine while generating DNA adducts. 13-Hydroxyellipticine may have potentially higher biological efficiencies than ellipticine, because it does not need enzymes for its activation and formation of DNA adducts. The aim of the diploma thesis was to synthesize this ellipticine derivative. 9- Nitroellipticin (another derivative of ellipticine) is an intermediate product of the 13- hydroxyellipticine synthesis. Results of this diploma thesis show that 9-nitroellipticine is oxidized by liver microsomal systems, which contain cytochromes P450, forming at least 4 metabolites. 9-Nitroellipticine shows similar behavior as ellipticine. Another...
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Enzymes metabolizing drugs
Škodová, Petra ; Stiborová, Marie (advisor) ; Kubíčková, Božena (referee)
Mixed function oxidase system (MFO) is one of the most effective systems of enzymes of the first phase of biotransformation of xenobiotics. Cytochromes P450 seem to be the most important part of the MFO system, which also contains other components such as NADPH:CYP reductase and membrane lipids. Cytochromes P450 function as a terminal oxidase of the mixed function oxidase (MFO) system. Many xenobiotics, including drugs, are the substrates of these enzymes. Endogenous substances can serve as the substrates of these enzymes as well. Peroxidases are a group of enzymes which are able to metabolize drugs. The function of cytochromes P450 can be substituted by peroxidases. Both groups of enzymes are able to potentiate the effect of the drugs by activating them or they form deactivated metabolites, which are excreted from the organism. The action of cytochromes P450 and peroxidases is shown on the metabolism of the drug ellipticine. Ellipticine has anticancer effects. The advantage of this drug is its low number of side-effects. The oxidation of ellipticine by cytochromes P450 and peroxidases leads to its metabolic activation or detoxification. Carbenium ions are generated by spontaneous cleavage of two active metabolites, 12-hydroxyellipticine and 13-hydroxyellipticine. Carbenium ions then form adducts...
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Driving forces of land use changes in the Czech Republic
ŠKODOVÁ, Petra
In this thesis entitled "The driving forces causing the changes of land use in the Czech Republic" is a comprehensive overview of the major historical events and milestones affecting land use in the Czech Republic and abroad. The first part is devoted to the historical development of land use in Europe from prehistory to the modern times. Special attention is paid to the development of land use in the Czech Republic in the 19th and 20th centuries, whose events are immediately reflected in the subsequent development of land use in our country. An integral part of the work is examined in detail the current land use CR with factors affecting its current form. There are presented pictures and tables comparing the current land use with the land use of previous years, in the Czech Republic as well as internationally. Furthermore the thesis assesses the factors that affect land ownership in the country. Significant attention was paid to the work in determining the driving forces of land use changes and their comparison with Europe and the world. Except the natural driving forces, the work in detail evaluate social driving forces and a significant impact of grants, subsidies, financing and international organizations.
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