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Synthesis of coumarin based fluorophore probes
Koutníková, Barbora ; Doležal, Martin (advisor) ; Nováková, Veronika (referee)
Charles University Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Student: Barbora Koutníková Supervisor: prof. PharmDr. Martin Doležal, Ph.D. Consultant: prof. Janez Ilaš, M. Pharm., Ph.D. Title of diploma thesis: Synthesis of coumarin based fluorophore probes Cancer remains to be one of the leading causes of death worldwide. Despite the progress in anti-cancer treatment, therapy of cancer is still associated with many disadvantages including an absence of selectivity as a major issue. The aim in development of chemotherapeutic drugs is to prepare more selective and better tolerated anti-cancer agents. Topoisomerases play an important role in the therapy of bacterial infections as well as anti-cancer treatment. Both types (human topo I and II) can be targeted during anti-cancer therapy. Isoform IIα is overexpressed during proliferation of the cell and therefore it is characteristic for cancer cells. Inhibition of this isoform leads to excessive DNA damage or to malfunctions during cell proliferation and consequently to cell apoptosis. This is why inhibitors of topoisomerase IIα are studied as candidates for anti-cancer therapy. The aim of this work was to prepare three compounds that would be later tested for inhibitory activity on human topoisomerase IIα. Optimization of the...
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Synthesis and study of subphthalocyanines axially modified with an amino adamantyl
Danková, Eva ; Nováková, Veronika (advisor) ; Demuth, Jiří (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Candidate Eva Danková Supervisor doc. PharmDr. Veronika Nováková, Ph.D. Title of Thesis Synthesis and study of subphthalocyanines axially modified by amino adamanthyl Photodynamic therapy is a promising approach for cancer treatment that relies on the administration of a photosensitizer, followed by illumination of the tumor. The generated oxidative stress subsequently activates several mechanisms of cell death. One of the novel groups of photosensitizers are subphthalocyanines with a conical π surface, which renders them less prone to aggregation and offers the possibility to tune their properties through axial substitution (aside peripheral modification). Due to the lipofilicity of the macrocycle, it is necessary to increase its water solubility. This work focused on the possibility of forming supramolecular host-guest complexes with hydrophilic macrocycles in order to increase the hydrophilicity of a subphthalocyanine. In particular, cucurbituril-7 (CB[7]) was chosen since it forms one of the most stable supramolecular interactions in water with 1-aminoadamantane, which was therefore proposed as the axial substituent on subphthalocyanine core. Synthesis of the...
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Detection of human adenoviruses from the respiratory samples from the patients of Motol University Hospital
NOVÁKOVÁ, Veronika
Human adenoviruses are world-wide pathogens causing endemic and epidemic outbre-aks of disease. Adenoviral infections are related with high morbidity and mortality especially among the paediatric allogeneic haematopoietic stem cell recipients. Presented work is comparing the commercial and in-house assay for detection of the adenoviruses to improve the diagnostics of these viruses in Motol University Hospital, especially among the immunocompromissed patients, in which is the rapid and precise detection highly important. Theoretical part of work presents the characteristics of adenoviruses, clinical symptoms and diseases of the adenoviral infection, their use in the experimental therapy. Practical part is aiming the screening of the respiratory tract samples with quantitative in-house test and comparing of the results with previously performed detection by commercial Anyplex TM II RV16 test. Detection of adenoviruses was performed in 1,881 samples from 1,420 patients with symptoms of respiratory tract infection by real-time PCR. In total, adenovirus was detected in 187 samples (9.9%) from 169 patients (11.9%). One hundred samples (53.5%) was positive by both methods, 26 (13.9%) with commercial detection only and 61 (32.6%) was positive only with in-house assay. Most frequently, adenoviruses were detected among the patients from Dept. of Paediatrics, Dept. of Paediatric Haematology and Oncology and from adult patients from 3rd Dept. of Surgery and Dept. of Anaestesiology, resuscitation and intensive medicine. In all positive samples, subsequent sequence analysis of hypervariable part of 1-6 hexon gene was performed and representative sequence for identification was obtained in 70 samples. Most frequently detected adenovirus genotypes were C2 (25.7 %), A31 (24.3 %), B3 (15.7 %) a C1 (11.4 %). From 26 samples positive by Anyplex TM II RV16, only 3 samples were identified (all as genotype B3). Contrary, among 61 positive samples detected only with in-house assay, 15 samples were identified as genotype A31 and 3 as AdV from group C. Our results shows the lower sensitivity of the commercial test in detection of adenoviru-ses.
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Perception of parental allowance from the parents' in intact families perspective
Nováková, Veronika ; Hejzlarová, Eva (advisor) ; Štěpánková Štýbrová, Martina (referee)
The main goal of this bachelor thesis is to describe how parental allowance is perceived in complete families. Due to the comparison of individual respondents, incomplete families, in which men or women who take care of a child independently, are not included in the sample. The parental allowance is one of the most important benefits provided by the state social support system, and its main task is to improve the financial situation of families with children. In addition to the parental allowance, this bachelor thesis also describes the system of social support, and other benefits whose purpose is to improve the financial situation of families in the Czech Republic. It also focuses on qualitative interviews with representatives of these families who receive parental allowance. Based on the analysis of these interviews, it describes how the interviewed families manage the parental allowance, how important the income is for them, and what opinions are associated with the parental allowance. The most important category which is connected with this allowance is certainty, which this regular allowance represents. Problems, which are discuss in this thesis are missing of motivational component and informations about parental allowance. Furthermore, this bachelor's thesis emphasizes the theory of special...
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Study of the effect of macrocycle on intramolecular charge transfer at phthalocyanines
Bednárik, Štefan ; Nováková, Veronika (advisor) ; Miletín, Miroslav (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department: Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Candidate: Štefan Bednárik Supervisor: doc. PharmDr. Veronika Nováková, Ph.D. Consultant: PharmDr. Jiří Demuth, Ph.D. Diploma thesis: Study of the effect of macrocycle on intramolecular charge transfer at phthalocyanines Porphyrazine derivates phthalocyanines (Pcs) and their aza-analogues (AzaPcs) have been largely investigated in number of applications due to their unique photophysical and photochemical properties. One of the investigated research areas involves intramolecular charge transfer (ICT) - deactivation of excited states. This phenomenon is a competitive pathway to fluorescence emission and requires electron donors as peripheral substituents while the macrocyclic core serves as electron acceptor. The aim of this work was to study how modifications to the Pc macrocycle will affect its electron acceptor properties and subsequently the strength of ICT. The synthesis involved preparation of suitable precursors, i.e. 4,5-disubstituted phthalonitriles or 5,6-disubstituted pyrazine-2,3-dicarbonitriles. It was followed by their cyclotetramerization leading to the mixture of six different congeners, from which the desired asymmetrical ABBB type macrocycle was...
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Synthesis and study of subphthalocyanines axially modified with an amino adamantyl
Danková, Eva ; Nováková, Veronika (advisor) ; Demuth, Jiří (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Candidate Eva Danková Supervisor doc. PharmDr. Veronika Nováková, Ph.D. Title of Thesis Synthesis and study of subphthalocyanines axially modified by amino adamanthyl Photodynamic therapy is a promising approach for cancer treatment that relies on the administration of a photosensitizer, followed by illumination of the tumor. The generated oxidative stress subsequently activates several mechanisms of cell death. One of the novel groups of photosensitizers are subphthalocyanines with a conical π surface, which renders them less prone to aggregation and offers the possibility to tune their properties through axial substitution (aside peripheral modification). Due to the lipofilicity of the macrocycle, it is necessary to increase its water solubility. This work focused on the possibility of forming supramolecular host-guest complexes with hydrophilic macrocycles in order to increase the hydrophilicity of a subphthalocyanine. In particular, cucurbituril-7 (CB[7]) was chosen since it forms one of the most stable supramolecular interactions in water with 1-aminoadamantane, which was therefore proposed as the axial substituent on subphthalocyanine core. Synthesis of the...
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Oxidation of a psychoactive substance fluoromethoxyacetyl fentanyl
Krejčí, Michaela ; Kubíček, Vladimír (advisor) ; Nováková, Veronika (referee)
7 2. ABSTRACT Fluoromethoxyacetyl fentanyl (FMAcF) is a new psychoactive substance that belongs to the group of newly illegally synthesized fentanyl derivatives that have been entering the European drug market since 2009. The aim was to define the electrochemical behavior of FMAcF and to suggest possible oxidation mechanisms. In this research, the electrochemical methods and in situ UV-Vis spectroelectrochemistry were used to study drug oxidation and reduction mechanism. Electrochemical techniques were combined with high performance liquid chromatography with diode array detector. FMAcF in the aqueous medium provided a single oxidation peak whose potential depended on pH. The substance was not reduced under the studied conditions. UV-Vis spectroelectrochemistry showed the formation of a reaction intermediate. The substance was electrolyzed and the UV-Vis absorption spectra of the products were determined. The oxidation mechanism of the substance has been proposed. In future the incubation with liver microsomes will be performed to detect metabolic pathways. Key words: Cyclic voltammetry, Oxidation, Bioactive substance, Fentanyls, Fluoromethoxyacetyl fentanyl
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Synthesis and evaluation of N-pyridylbenzamides as potential antimicrobial compounds
Suchánková, Eliška ; Zitko, Jan (advisor) ; Nováková, Veronika (referee)
SYNTHESIS AND EVALUATION OF N-PYRIDYLBENZAMIDES AS POTENTIAL ANTIMICROBIAL COMPOUNDS Eliška Suchánková Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic The derivatives of N-pyridylbenzamide were designed and synthesized to be in vitro tested for antimycobacterial activity against Mycobacterium tuberculosis H37Ra, M. smegmatis, M. aurum and in vitro cytotoxicity in HepG2 cells. These compounds are pyridinyl analogues of previously prepared N-pyrazinylbenzamides that have shown a significant in vitro antimycobacterial activity. The title compounds were synthesized by acylation of aminopyridine or chloropyridine-2-amine by selected benzoyl chlorides. Final compounds were described by elementary analysis, melting point, 1 H and 13 C spectra and IR spectroscopy. Generally, prepared compounds possess lower antimycobacterial activity than previously tested N-pyrazinylbenzamides. However, there are some cases, in which the derivatives of pyridine were more effective compared to the derivatives of pyrazine; mainly against M. smegmatis. The best antimycobacterial activity was proved for derivatives of 2-amino-6-chloropyridine and substituted benzoyl chloride, corresponding with higher lipophilicity of these compounds;...
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The death of Tsar Nicholas II and its reverberations in contemporary Czech environment
Nováková, Veronika Kateřina ; Čechura, Jaroslav (advisor) ; Šmíd, Marek (referee)
The main goal of the bachelor thesis "The death of Tsar Nicholas II and its reverberations in contemporary Czech environment" is to paint a compehensive picture of the death of the family of Russia's last Tsar and its reverbations in former Czechoslovakia. The text recounts the life and reign of Nicholas II with a closer focus on the murder of all family members in July 1918. It places the last moments of the Tsarist regime along with its sovereign in the context of contemporary Czech environment. It delves into the reverbations of Tsar's death and the coming of a new regime in Czech press, and the cultural and political scenes.
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