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SYNTHESIS OF UNSYMMETRICAL DERIVATES OF AZAPHTALOCYANINES FOR THE THIRD GENERATION OF PHOTOSENSITISERS AND SYNTHESIS OF THEIR PRECURSORS
Šlajsová, Dana ; Zimčík, Petr (advisor) ; Kučerová, Marta (referee)
SYNTHESIS OF UNSYMMETRICAL DERIVATES OF AZAPHTALOCYANINES FOR THE THIRD GENERATION OF PHOTOSENSITISERS AND SYNTHESIS OF THEIR PRECURSORS Slajsova Dana Department of Pharmaceutical Chemistry and Drug Control, Faculty of Pharmacy in Hradec Králové, Charles University in Prague Unsymmetrical zinc complexes of azaphtalocyanines (AzaPc) of tetrapyrazinoporphyrazine type with one carboxylic acid (AAAB) were synthesized using statistical condensation of 5,6-bis(tert-butylsulfanyl)pyrazine-2,3- dicarbonitrile (A) with 6-(3-tert-butylsulfanyl-5,6-dicyanopyrazine-2- ylamino)hexanoic acid (B1) or 3-(5,6-dicyano-3-methyl-pyrazine-2- ylsulfanyl)propionic acid (B2). These precursors were chosen because each of them takes advantage of suitable properties to application of AzaPc in photodynamic therapy. These properties are demonstrated in final products too. Bulky tert- butylsulfanyl ensures good monomerisation of planar moleculs of AzaPc in a solution and consequently allows efficient separation and purification. Positive influence of alkylsulfanyl substituent on singlet oxygen production has been already shown earlier. Carboxy group that can be further functionalized (e.g. conjugation with biomolecules) brings into the AzaPc the modifiable moiety. The standard cyclization process with anhydrous zinc acetate was applied....
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Synthesis of unsymmetrical derivatives of azaphthalocyanines II.
Šlajsová, Dana ; Zimčík, Petr (advisor) ; Kučerová, Marta (referee)
SYNTHESIS OF UNSYMMETRICAL DERIVATES OF AZAPHTALOCYANINES II. Slajsova Dana Department of Pharmaceutical Chemistry and Drug Control, Faculty of Pharmacy in Hradec Králové, Charles University in Prague Magnesium complexes of unsymmetrical azaphtalocyanines (AzaPc) of tetrapyrazinoporphyrazine type with one carboxylic acid were synthesized using statistical condensation of 5,6-bis(tert-butylsulfanyl)pyrazine-2,3-dicarbonitrile (A) and 6-(3-tert-butylsulfanyl-5,6-dicyanopyrazine-2-ylamino)hexanoic acid (B). These two products were chosen because each of them takes advantage of suitable properties to application of AzaPc in photodynamic therapy. These properties are demonstrated in final product too. Bulky tert-butylsulfanyl ensures good monomerisation of planar moleculs of AzaPc in a solution and consequently allows efficient separation and purification. Positive influence of alkylsulfanyl substituent on singlet oxygen production has been already shown earlier. Carboxy group, that can be converted in other reactions (esterification, conjugation with biomoleculs) brings into the AzaPc the modifiable moiety. The standard cyclization process in butanol in the presence of magnesium butanolate was applied. 2,2-dimethylpropane-1-thiol was liberated during the reaction. Probably, it was due to nucleophilic attack of...
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Derivatives of Rhodanine as Potential Drugs I
Kešetovičová, Diana ; Opletalová, Veronika (advisor) ; Kučerová, Marta (referee)
Diploma thesis title: RHODANINE DERIVATIVES AS POSSIBLE THERAPEUTICS I. Author: Diana Kešetovičová ABSTRACT The raise of microbial resistance towards commonly used antimicrobial agents enhances the need for new active substances with novel modes of action. Rhodanine (2-thioxo-1,3-thiazolidin-4-one) represents a structural motif that has not yet been applied in any antimicrobial drug. Rhodanine derivatives have already been described as substances possessing a wide spectrum of biological activity. Within this diploma thesis, condensation products of rhodanine and 3-(2- hydroxyethyl)-rhodanine with ortho-, meta- and para-substituted nitro- benzaldehydes have been prepared. The reaction was carried out in water- alcoholic medium using NH4OH/NH4Cl as a catalyst. The antifungal and antimycobacterial properties of these derivatives and their inhibitory activity on photosynthetic processes were then evaluated. A medium antifungal activity against C. albicans, T. asahii, T. mentagrophytes and A. fumigatus have been observed with the N-unsubstituted derivatives, while the N-substituted derivatives were inactive. The antimycobacterial properties of the tested compounds were not high enough (inhibition of at least 90% in the primary test) to undergo further studies. The antimycobacterial activity of the N-substituted...
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Chalcones and Their Analogues as Potential Drugs IX
Kopcová, Petra ; Kučerová, Marta (advisor) ; Doležal, Martin (referee)
7.2 Příloha 2 Abstract of the diploma thesis CHALCONES AND THEIR ANALOGUES AS POTENTIAL DRUGS IX. Petra Kopcová 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 In the theoretical part of this diploma thesis, the beneficial effects of chalcones on cardiovascular diseases are summarized. Possible mechanisms of action of synthetic and naturally occurring compounds are mentioned too. Both expected and documented effects are described. The experimental part deals with the products of Claisen-Schmidt condensation. Pyrazine analogues of chalcones with methoxy-group in the position 4 of the phenyl ring B and different alkyls in the position 5 of pyrazine ring A were synthesized. Also some intermediate products for the condensation were prepared. Five final products resulted from the experimental work. None of them has been described in literature yet. The compounds were characterized by their melting point, NMR and IR spectra. Their purity was verified by thin-layer chromatography and elemental analysis.
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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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