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Acyclic nucleosides of 3-hydroxypyrazine-2-carboxamide bases
Chaloupecká, Ema ; Jindřich, Jindřich (advisor) ; Smrček, Stanislav (referee)
This thesis deals with the preparation of acyclic nucleosides and nucleoside phosphonates of compounds T-705 (6-fluoro-3-hydroxypyrazine-2-carboxamide) and T-1105 (3-hydroxypyrazine-2-carboxamide). Acyclic nucleoside phosphonates are substances that can terminate viral RNA or DNA replication, and some of them are used in the treatment of viral diseases. T-705 and T-1105 have shown activity against the influenza virus, and T-705 has already been approved for its treatment in Japan. Since both compounds mimic natural nucleobases in the body, their acyclic nucleosides and nucleoside phosphonates also have the potential to be biologically active. Methods for the synthesis of 3-fluoro-2-(phosphonomethoxy)propyl and 3-hydroxy-2-(phosphonomethoxy)propyl derivatives of T-705 and T-1105, their prodrugs containing lipophilic groups for the improvement of the pharmacokinetic properties and also their phosphonate diphosphates, suitable for the biological activity measurements, have been proposed. Some of these derivatives were subsequently prepared. Key words: acyclic nucleosides, acyclic nucleoside phosphonates, T-705, T-1105, favipiravir, antiviral activity, influenza
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Interaction of selected cosmetic additives with biotransformation enzymes
Bušovská, Radka ; Hodek, Petr (advisor) ; Smrček, Stanislav (referee)
Substances which cause an endocrine dysfunction have a negative impact on the human body and can be found all around us. One of the main mechanisms of their action is the binding to cell receptors or the inhibition of key enzymes involved in steroid hormone synthesis. In this study, the inhibitory effect of selected perfumes and car air fresheners on the activity of aromatase, the key enzyme of steroidogenesis, was examined. Aromatase converts male sex hormones into the female ones. Inhibition of this enzyme results in decreased estrogen concentrations and may thus affects human fertility. The aromatase activity was examined based on the aromatization reaction of testosterone into estradiol. The formation of estradiol was monitored by TLC method. Based on the results of the pilot study the tested perfumes do not significantly inhibit the aromatase activity, while air fresheners in cars appear to be potential aromatase inhibitors. Keywords: Endocrine dysfunction, steroidogenesis, aromatase, perfumes, air fresheners, TLC, chromatography
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Interaction of selected cosmetic additives with biotransformation enzymes
Bušovská, Radka ; Hodek, Petr (advisor) ; Smrček, Stanislav (referee)
Endocrine disruptors are nowadays very often discussed, due to their negative impact on the human body. They can be found all around us and they've become a parf of our everyday life, even if many people don't even realize it. Cosmetic products and perfumes are part of everyday life and just few of many people realize the consequences of having regular contact with our skin. Perfumes and fragrances are part of all cosmetic products or various commonly used industrial products, that people could not even live without. Perfumes can have a negative effect on the health of the organism and, due to the large number of chemicals they consist of and the interactions with each other and the subsequent interaction with important enzymes such as aromatase, they can belong to the group of hormone-active substances. The aim of this work was to find out by TLC (Thin Layer Chromatography) analytical method whether various perfumes and industrial car smells can disturb the endocrine system by inhibiting the key enzyme, aromatase. Experiments have shown that the commonly used fragrances really interact with aromatase. Keywords: Endocrine disruptors, aromatase, TLC, chromatography, perfumes, industrial fragrances
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Phytoextraction of Benzodiazepines from Water Solutions
Grasserová, Alena ; Smrček, Stanislav (advisor) ; Soudek, Petr (referee)
Abstract, key words The aim of this thesis was to perform a phytoextraction experiment with benzodiazepines chlordiazepoxide, diazepam, alprazolam and bromazepam on corn plant (Zea mays). After 14 days of growing of sterile cultivation, new medium (Murashige and Skoog) contaminated with benzodiazepine was added. The starting concentration of benzodiazepine was 10 mg · l-1. After every 24 hours, a sample of medium was collected. The actual concentration of benzodiazepine was measured on HPLC with UV detection. Extractable residues were also analysed to find out whether the benzodiazepine is being translocated to the upper parts of the plant. The same HPLC conditions were used for these samples. The greatest phytoextraction efficiency (the amount of drug extracted by 1 gram of biomass in 24 hours) was observed for chlordiazepoxide, followed by bromazepam, alprazolam and diazepam respectively. The extractable residues analysis confirmed the translocation to the upper parts of the plant for every of the benzodiazepines tested. That indicates a threat for the animals through the food chain contamination. Key words: phytoremediation, phytoextraction, benzodiazepines, extractable residuals, HPLC.
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Biosynthesis of the bumblebee male pheromones and its hormonal regulation.
Bártová, Adéla ; Valterová, Irena (advisor) ; Smrček, Stanislav (referee)
Bumblebees are important pollinators, commercially used in large-scale plant growing in greenhouses. Their males produce marking pheromones for mating, which attract young bumblebee queens. These pheromones are often a complicated mixture of chemicals, which is produced in the male labial gland, and the mixture itself is specific for each bumblebee species. The regulation of bumblebee sexual pheromone biosynthesis is largely unknown, and this Master's thesis is focused on the analysis of the mechanisms which lead to the regulation of the Bombus terrestris male pheromone's fat-acid and terpenes biosynthesis, specifically on stereospecific enzymatic reduction of double bond of farnesol. This thesis studies the influence of potential neurohormones on a specific enzymatic mixture, which is involved in the pheromone biosynthesis. Methods used in this project include biochemical, analytic and molecular-biology methods.
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The study of interactions of drug residues with higher plants
Štrosová, Sofie ; Smrček, Stanislav (advisor) ; Soudek, Petr (referee)
Psychotropic agents are currently commonly used drugs. Their consumption increases dramatically, thus increasing the possibility of environmental contamination. Although these substances are largely metabolized, some of them are excreted through urine into municipal wastewater. Wastewater treatment plants only partially remove these micropolutants. Water effluent from wastewater treatment plants enter surface flows and through them pollutants are spread in the aquatic ecosystem and can contaminate terrestrial organisms. The interaction of drugs with plants provides us with information about the possible use of biotechnological decontamination technology - phytoremediation. In addition, the same process shows us the possibility of contamination of food chains of humans and animals, where these pollutants can cause changes in behavior and reproduction. The active substances trazodone and hydroxyzine are frequently prescribed drugs. The possibility of their phytoextraction and their uptake by the root system of corn plants (Zea mays) in an in vitro sterile model system was studied. Plants were cultivated on Murashige-Skoog medium. After adequate growth, medium with the studied pollutant with concentration 5 mg/L and 10 mg/L was added to the cultivations. The decrease in drug concentration in the...
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Cyclodextrin derivatives containing covalently bound volatile substances and studies of their release
Palágyi, Attila ; Jindřich, Jindřich (advisor) ; Smrček, Stanislav (referee)
The main aim of the work was to prepare a series of β-cyclodextrin derivatives containing covalently bound volatile compounds via an imine bond. The used volatile compounds were cinnamaldehyde, cyclamen aldehyde, lilal, benzaldehyde, anisaldehyde, vanillin, hexanal, heptanal, citral and 5-methylfurfural. Subsequently, the rate of the release of the active compound, as a function of the environment, was studied by 1 H NMR spectroscopy and static headspace-gas chromatography. Key words: cyclodextrin, aldehyde, imine, kinetics, controlled release
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Utilization of mass spectrometry for analysis of biologically active compounds
Kaliba, David ; Jelínek, Ivan (advisor) ; Pacáková, Věra (referee) ; Smrček, Stanislav (referee)
This PhD thesis provides a commented set of four publications. These publications are focused on capillary electrophoresis, liquid chromatography, and UV/Vis spectrometry used to study complexes of rhenium with aromatic ligands. The methods of mass spectrometry with soft ionization techniques, 1 H and 13 C nuclear magnetic resonance, and infrared spectrometry were used for structural characterization of the individual complexes. The complexes were synthetized in reactions of the rhenium precursor tetrabutylammonium tetrachlorooxorhenate with the corresponding ligand under both aerobic and anaerobic conditions. In the course of the research, it was revealed that the prepared complexes (with Re in the oxidation number +V and +VI) are unstable and their oxidation numbers change to another more stable form (Re+VII ). Sub-projects which were successfully implemented during the research were as follows: Design and successful realization of the process of synthesis of selected rhenium complexes with aromatic ligands 1,2-dihydroxybenzene, 1,2,3-trihydroxybenzene, and 2,3-dihydroxynaphthalene in reactions with and without air access, and their structural characterization by ESI-MS, APPI- MS, LDI-MS, ESI-MS/MS, NMR, and IR. ESI-MS SRM and UV/Vis time studies of the behaviour of primary rhenium complexes...
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