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National Repository of Grey Literature 2 records found  Search took 0.00 seconds. 
Chemical and biochemical transformation of bioactive compounds
 Šimášková, Ema ; Sokolová, Romana (advisor) ; Martínková, Markéta (referee)
Xenobiotics, such as pharmaceuticals, food additives, environmental pollutants, and dietary bioactive compounds in organism are metabolized by various enzymes, resulting in their bioactivation or detoxification. Identification of structure of resulting metabolites is important for their detection in bodily fluids and tissues for diagnostic and forensic purposes. This thesis reviews known biochemical processes and enzymes involved in xenobiotic metabolism, including cytochromes 450 (CYP) and flavine monooxygenases (FMO). Given that biochemical reactions are to a major extent composed of electron-transfer reactions (i.e. oxidation and reduction), the thesis includes a section dealing with the practical approaches to determination of the oxidative or reductive mechanism of bioactive compounds.
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Metabolism of tyrosine kinase inhibitor cabozantinib by rat liver microsomes
 Jurečka, Tomáš ; Indra, Radek (advisor) ; Mrízová, Iveta (referee)
Cabozantinib is an anticancer drug that was approved for treatment of progressive thyroid cancer by FDA and EMA organizations. Cabozantinib is a tyrosine kinase inhibitor. It blocks signal pathway receptors that are important for growth of tumors. This bachelor's thesis describes the findings about the metabolism of cabozantinib. It studies metabolism of cabozantinib in hepatic microsomes isolated from various laboratory animals (rat, mouse and rabbit) and impact of particular isoforms of cytochromes P450 (CYP) on metabolism of cabozantinib in rat hepatic microsomes. The bachelor's thesis also describes the optimization of method for separation metabolites of cabozantinib by high performance liquid chromatography (HPLC) and also identification of metabolites using mass spectrometry. Up to three different metabolites were detected by utilizing hepatic microsomes isolated from various laboratory animals. Those were M1, monohydroxycabozantinib and O-desmethylcabozantinib. Mouse microsomes oxidized cabozantinib mainly to O-desmethylcabozantinib and rabbit microsomes metabolised cabozantinib mainly to monohydroxycabozantinib. Microsomes from controlled rats produced two metabolites with the overall majority of monohydroxycabozantinib. The highest number of metabolites was produced by microsomes from...
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