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Synthesis of model water-soluble azaphthalocyanine fluorescence quencher
Subara, Ljiljana ; Zimčík, Petr (advisor) ; Opletalová, Veronika (referee)
1 Abstract Faculty of Pharmacy in Hradec Králové, Charles University in Prague Department of Pharmaceutical Chemistry and Drug Control Ljiljana Subara Synthesis of Model Water-Soluble Azaphthalocyanine Fluorescence Quencher Azaphthalocyanine (AzaPc) or tetrapyrazinoporphyrazine as they are often termed in literature, and its substituted derivatives have been investigated extensively for applications as photodynamic therapeutics, dyes, catalysts, liquid crystals, non-linear optical materials and as a red fluorophore. Quenching in general is a process that decreases the fluorescence of another compound. Azaphthalocyanine quenchers are synthetic dyes that decrease fluorescence by absorbing energy over a wide range of wavelengths to dissipate their absorbed energy as non fluorescence. However, in order to do so they must remain in close contact with the fluorescent compound. In this work, we describe the approaches used for the synthesis of azaphthalocyanines (AzaPc) and ways to increasing quenching properties while attaining water solubility. We synthesized a compound which had water solubility as a hydrochloride and no aggregation, however it lacked sufficient quenching properties, and remained difficult to purify on TLC. For improvement of quenching an alternative precursor substituted with a tertiary amine...
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Synthesis of precursors for biologically active lactones IV.
Bémová, Hana ; Opletalová, Veronika (advisor) ; Kuča, Kamil (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Kralove Department of Pharmaceutical Chemistry and Drug Control SYNTHESIS OF PRECURSORS FOR BIOLOGICALLY ACTIVE LACTONES IV. Rigorous Thesis Hana Piskacova A high width of biological activity of natural or synthetic unsaturated five membered lactones from the family of furan-2(5H)-ones, is the main reason why to synthesize new substances of this structure. The introductory part of the thesis deals with antineoplastic natural compounds of this type. Except of antitumour activity some unsaturated five membered lactones exhibit antifungal, antiviral, antibacterial effects, or inhibit the synthesis of cholesterol, for example. The experimental project is an extension of my diploma thesis concerned with the synthesis of precursors for lactones. These precursors - methyl (E)- and (Z)-2-bromo-5- (subst.)arylpent-2-en-4-ynoates - were prepared by Sonogashira couplings. The parent substances for couplings were arylethynes (1-ethynyl-4-(methoxymethoxy)benzen, 1-ethynyl-2-nitrobenzene, 3-ethynylaniline, 2-ethynylpyridine) and methylesters of dihalogenated prop-2-enoic acid. The dominant products of the couplings were β-monoalkynylated esters, apart from them side products of homocouplings were obtained. Reactions of E-methylesters of dihalogenated...
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Acetylpyrazines as intermediates for the synthesis of biologically active derivative of pyrazine III.
Zobalová, Dana ; Opletalová, Veronika (advisor) ; Palát, Karel (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Drug Analysis Candidate Mgr. Dana Honcová-Zobalová Consultant RNDr. Veronika Opletalová, Ph.D. Title of Thesis Acetylpyrazines as intermediates for the synthesis of biologically active derivatives of pyrazine III. The rigorous thesis is aimed at the preparation of 5-alkylpyrazin-2-carbonitriles, 5-alkyl-2-acetylpyrazines and their thiosemicarbazones and N,N-dimethylthiosemicarbazones. N,N-dimethylthiosemicarbazone of acetophenone was prepared for comparison. Theoretical part deals with the structure and properties of thiosemicarbazones and their biological effects. The following compounds were prepared and characterized during experimental work: 5-isopropylpyrazin-2-carbonitrile 5-pentylpyrazin-2-carbonitrile 5-hexylpyrazin-2-carbonitrile 5-heptylpyrazin-2-carbonitrile 1-(5-isopropylpyrazin-2-yl)ethan-1-one 1-(5-pentylpyrazin-2-yl)ethan-1-one 1-(5-hexylpyrazin-2-yl)ethan-1-one 1-(5-heptylpyrazin-2-yl)ethan-1-one 1-(5-hexylpyrazin-2-yl)ethan-1-one thiosemicarbazone 1-pyrazin-2-ylethan-1-one N,N-dimethylthiosemicarbazone 1-(5-pentylpyrazin-2-yl)ethan-1-one N,N-dimethylthiosemicarbazone 1-(5-hexylpyrazin-2-yl)ethan-1-one N,N-dimethylthiosemicarbazone ...
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Synthesis of novel hybrid molecules combining an M1 agonist and acetylcholinesterase inhibitors
Kerhartová, Markéta ; Kučerová, Marta (advisor) ; Opletalová, Veronika (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Drug Analysis Student: Markéta Kerhartová Supervisor: PharmDr. Marta Kučerová, Ph.D. Consultant: PharmDr. Jan Korábečný, Ph.D. Title of diploma thesis: Synthesis of novel hybrid molecules combining an M1 agonist and acetylcholinesterase inhibitors Alzheimer's disease (AD) is a neurodegenerative disorder of complex etiology, with insidious progression and fatal consequences. Its global incidence rates are very high, rising in line with the aging population. AD is manifested as a progressive decline of cognitive and intellectual functions. Histopathological hallmarks include the presence of β-amyloid neuritic plaques, neurofibrillary tangles composed of hyperphosphorylated τ protein and atrophy of brain tissue. Neurotransmitter levels are decreased in case of acetylcholine (ACh) while glutamate levels are elevated. Nowadays, there are two pharmacological groups employed in the treatment of AD: acetylcholinesterase inhibitors (AChEIs) and antagonist of N-methyl-D-aspartate receptors (NMDARs) - memantine. Both groups act only symptomatically, not having disease-modifying effect. The aim of our study was preparation of a series of novel hybrid molecules combining AChEIs, namely tacrine, 7-methoxytacrine...
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Chalcones and their analogues as potential drugs X.
Richterová, Lenka ; Opletalová, Veronika (advisor) ; Kučerová, Marta (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Drug Control Candidate Mgr. Lenka Richterová Consultant Assoc. Prof. RNDr. Veronika Opletalová, Ph.D. Title of Thesis Chalcones and their analogues as potential drugs X. Theoretical part of the thesis is devoted to current possibilities in the treatment of mycoses. Some examples of natural chalcones with antifungal properties are given, and various modifications of their structures and the influence of these modifications on antifungal activity are described. Experimental part deals with the synthesis of fluorinated (2E)-3-phenyl-1-pyrazin-2-ylprop-2-en-1-ones (Obr. 1). N N O R 1 R 2 R1 = H, tert-butyl, isobutyl, butyl, propyl R2 = 2-F, 4-F Obr. 1 Structure of the studied compounds The compounds were obtained by the Claisen-Schmidt condensation in pyridine using diethylamine as condensing agent. The syntheses yielded one compound already reported in literature and four novel analogs. The structures of the products were corroborated by means of IR a NMR spectra and their purity checked by melting point and elemental analysis. Antifungal activity of the prepared compounds was evaluated by microrodilution broth method against eight strains of pathogenic fungi. The highest potency in both...
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Synthesis of the 3rd generation of photosensitizers based on azaphthalocyanine core
Stará, Vendula ; Zimčík, Petr (advisor) ; Opletalová, Veronika (referee)
CHARLES UNIVERSITY IN PRAGUE FACULTY OF PHARMACY IN HRADEC KRÁLOVÉ DEPARTMENT OF PHARMACEUTICAL CHEMISTRY AND DRUG CONTROL Title: Synthesis of the 3rd generation of photosensitizers based on azaphthalocyanine core. Author's name: Vendula Stará Year: 2009 Abstract: Photodynamic therapy (PDT) is a new significant treatment modality for several diseases, most notably cancer. Light, oxygen and photosensitizing drug (PS) are combined to produce a selective therapeutic effect. An important breakthrough in PDT is searching for a new PS, modification of their photophysical and optical properties. In this my diploma thesis I synthesized butyl 2,3-dicyanoquinoxaline-6-karboxylate acid by esterification of carboxyl group through its chloride. I used this butylester to synthesize the symmetric and asymmetric AzaPc. The synthesis of the asymmetric AzaPc with one carboxy group in the structure was not possible, because the separation of A3B congener was strongly adsorbed on silica. Esterification of the carboxy group did not lead to better results. Further, I synthesized symmetric AzaPc with butyloxycarbonyl group on the periphery of makrocycle. I prepared zinc (II) dye from its metal-free derivative which was prepared from magnesium (II) analog.
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Pyrazine derivatives as potential drugs IV.
Valášek, Ondřej ; Doležal, Martin (advisor) ; Opletalová, Veronika (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Tutor - specialist: PharmDr. Jan Zitko, Ph.D. Candidate: Ondřej Valášek Title of diploma thesis: Pyrazine Derivatives as Potential drugs IV. Even in the year 2016, tuberculosis is still worldwide problem which is addressed by many national and supra-national organizations trying to eliminate it. It burdens the most developing countries which don't usually have the opportunity to access the potential of modern medicine to its full extent. In relation to ineffective treatment, there grows prevalence of tuberculosis, which can't be managed by standard treatment. There is an urgent need to find new compounds and change structures of current antituberculars, which will help us defeat multi-drug resistant M. tuberculosis. The objective of my work was to find out the influence of inversion of the amidic group in derivatives of pyrazin-2-carboxylic acid (-CO-NH- to -NH-CO-) and their efficacy and toxicity. In the theoretical part I focused on resuming all the basic facts about tuberculosis and its causing agent, about possibilities in prevention and diagnostics as well as the antituberculars, both used and currently tested, which can help us in the future. In the experimental part I wrote down the reactions and procedures, which were used...
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Acetylpyrazin-thiosemicarbazone analogues as potential drugs
Heczková, Jana ; Opletalová, Veronika (advisor) ; Kučerová, Marta (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Drug Control Candidate Mgr. Jana Heczková Consultant Doc. RNDr. Veronika Opletalová, Ph.D. Title of Thesis Acetylpyrazin-thiosemicarbazone analogues as potential drugs In the theoretical part of this thesis new findings on antifungal and antibacterial effects of thiosemicarbazones published in 2005 - 2012 were described. Thiosemicarbazones have a very broad range of antimicrobial activity, their effects are in many cases comparable or even better than already used pharmaceuticals. In the experimental part, the preparation procedures of thiosemicarbazones were described and following 7 compounds were prepared: (2E)-2-[1-(pyridine-2-yl)ethylidene]hydrazinecarbothioamide (2E)-2-[1-(pyridine-3-yl)ethylidene]hydrazinecarbothioamide (2E)-2-[1-(pyridine-4-yl)ethylidene]hydrazinecarbothioamide (2E)-2-[1-(2-hydroxyphenyl)ethylidene]hydrazinecarbothioamide (2E)-2-(2-hydroxybenzylidene)hydrazinecarbothioamide (2E)-2-[1-(2-hydroxyphenyl)ethylidene]-N,N-dimethylhydrazinecarbothioamide (2E)-2-(2-hydroxybenzylidene)-N,N-dimethylhydrazinecarbothioamide All prepared thiosemicarbazones were characterized by melting point, IR and NMR spectra. Purity was verified by elemental analysis. The...
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