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Synthesis of Precursors for Biologically Active Lactones III.
Šipulová, Zuzana ; Kučerová, Marta (advisor) ; Kopecký, Kamil (referee)
OF DIPLOMA THESIS Synthesis of Precursors for Biologically Active Lactones III. Zuzana Šipulová Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Chemistry and Drug Control In the theoretical part of the diploma thesis, diseases caused by fungi (mycoses), their treatment and also antifungal and other effects of furan-2(5H)-one-containing agents are summarized. Methyl-(E)-2-brom-5-(2-nitrophenyl)pent-2-en-4-ynoate has been synthesized within the scope of the experimental work. Methyl-(E)-2-brom-5-phenylpent-2-en-4-ynoate has been also synthesized in the experimental work as a starting ester for methyl-(E)-2-(arylethynyl)-5-phenylpent-2-en- 4-ynoates which have been obtained via coupling with different alkynes. Syntheses of some derivates have been optimized by modification of reaction conditions. Methyl-(E)- 2-(arylethynyl)-5-phenylpent-2-en-4-ynoates can be used as starting compounds for synthesis of potential biological active lactones.
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Derivatives of pyrazine as potential antituberculotics
Osička, Zdeněk ; Doležal, Martin (advisor) ; Kučerová, Marta (referee)
Mgr. Zdeněk Osička: Pyrazine Derivatives as potential antituberculous drugs I have focused on the synthesis of compounds from the class amides of substituted pyrazinoic acid in my Pharmacy Doctor Thesis. Series of compounds were prepared by the reaction of pyrazinoic acid chloride with corresponding amines. Synthesis underwent in two steps. Final compounds were characterized by the melting point, TLC, elementary analysis, 1H a 13C NMR and IR. All compounds were liable in vitro testing on their biological activity - antimycobacterial, antifungal and antibacterial. In the group of antituberculosis testing the activity grew up from the least to the most lipophility compound.
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Synthesis and comparison of activity of potential reactivators of acetylcholinesterase inhibited by cyclosarine
Lipka, Lukáš ; Doležal, Martin (advisor) ; Kučerová, Marta (referee)
SYNTHESIS OF POTENCIAL QUATERNARY ACETYLCHOLINESTERASE REACTIVATORS AND EVALUATION OF THEIR POTENCY TO REACTIVATE CYCLOSARIN-INHIBITED AChE Mgr. Lukáš Lipka Department of pharmaceutical chemistry and drug control, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic Abstract of the rigorous thesis: Nine potential AChE reactivators were synthesized. Their potency to reactivate AChE inhibited by cyclosarin nerve agent was tested in vitro. According to the obtained results, 1,4- bis(2-hydroxyiminomethylpyridinium)butane dibromide seems to be most potent AChE reactivator. The reactivation potency of these compounds depends on structural factors such as presence of quaternary nitrogens, lenght of the linking chain between both pyridinium rings, and position of the oxime moiety at the pyridinium ring. The independence of potency of reactivator trimedoxim at the kind of anion present in his molecule was validate.
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Steps towards the development of an in vitro assay of early endosome fusion
Švédová, Lucie ; Kučerová, Marta (advisor) ; Čečková, Martina (referee)
7. SHRNUTÍ Tato diplomová práce byla zpracována pod záštitou programu SOCRATES/ ERASMUS na Welsh School of Pharmacy v Cardiffu. Cílem mé práce bylo modifikovat již vyvinutou metodu (Wessling-Resnick M. et al., January 1990) a přizpůsobit ji podmínkám tamní laboratoře. Předmětem studia byla subpopulace tzv. časných endosomů, které vznikají těsně při povrchu plasmatické membrány po rozpadu klatrinového pláště. Jednou z jejich vlastností je schopnost spojovat se, fúzovat, čímž vzniká nadbytečná membrána potřebná pro další osud těchto organel. Ve svých experimentech jsem pracovala se dvěma komplementárními markery. Jedním z nich byl avidin navázaný na enzym -galaktosidasu, která štěpí kromě laktosy také syntetické substráty za vzniku příslušných produktů. V této studii byl produktem specifické hydrolýzy methylumbeliferylgalaktosidu intenzivně fluoreskující methylumbeliferon. Druhým markerem byl biotinylovaný transferin. Podstatou komplementarity markerů je vysoká afinita avidinu k biotinu. Dvě skupiny buněk byly inkubovány se zmíněnými markery a po jejich akumulaci v endosomech následovala mechanická destrukce buněk za uvolnění organel. Oba typy endosomů byly smíchány v prostředí podporujícím jejich fúzi. Spojením dvou endosomů nesoucích různé markery došlo k jejich rychlé kombinaci za vzniku komplexu...
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Synthesis of tetrapyridoporphyrazines with potential photodynamic activity
Vavrečková, Magda ; Zimčík, Petr (advisor) ; Kučerová, Marta (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department Department of Pharmaceutical Chemistry and Drug Control Candidate Magda Vavrečková Supervisor Doc. PharmDr. Petr Zimčík, Ph.D. Title of Thesis Synthesis of tetrapyridoporphyrazines with potential photodynamic activity Substituted tetrapyridoporphyrazines represent new structural type of potential photosensitizers with interesting properties for application in photodynamic therapy. The aim of this work was to synthesize two types of tetrapyridoporphyrazines with hydrophilic substituents as potential photosensitizers. Photosensitizers are substances with an ability to produce singlet oxygen after activation by light. Singlet oxygen is the key toxic species in photodynamic therapy. 2-Chloro-5,6-dimethylpyridine-3,4-dicarbonitrile (1) was prepared in the first step by condensation of tetracyanoethylene and butan-2-one. In the next step, a hydrophilic substituent was attached by nucleophilic substitution. The first precursor was prepared by reaction of compound 1 with 2-mercaptoethanol in the presence of sodium hydroxide. Similarly, the second precursor was obtained by reaction of compound 1 with diethylaminoethanol in the presence of sodium hydride. The third step involved cyclotetramerization with magnesium butoxide as...
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Chalcones and their analogues as potential drugs VII
Švédová, Lucie ; Kučerová, Marta (advisor) ; Palát, Karel, st. (referee)
CHALCONES AND THEIR ANALOGS AS POTENTIAL DRUGS VII Lucie Švédová Department of pharmaceutical chemistry and drug control, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic Abstract of the rigorous thesis: This synthetic thesis is focused on searching of potential drugs from the group of chalcone derivatives and links up to the long-term studied topic at our department. Antibacterial and antifungal effects are the main examined biological activities. In the theoretical part of this thesis there were arranged various antineoplastic effects of naturally occuring or synthetic chalcones. The bibliographic searches involve items from the last decade. Possible interventions on the level of control processes, proteosynthesis and nucleic acid synthesis, influence on mitosis, apoptosis and the P-glycoprotein and the action on angiogenesis and cancer invasivity were summarized. In addition antioxidant activity and other mechanisms of chemoprevention were introduced as well. Different methods of chalcone synthesis were summed up in conclusion. In the frame of the experimental part substituted derivatives and heterocyclic analogs of chalcones were synthetized by means of condensation reaction. All the synthetic products were characterized by...
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