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Solubilisation systems for potential photodynamic compounds III.
Grandová, Milada ; Kopecký, Kamil (referee) ; Miletín, Miroslav (advisor)
This graduation thesis is engaged in searching for solubilisation systems for potentially photodynamically active substances. The effort was focused on fading of systems with the smallest particles, transparent or modestly opalescent with the acceptable cytoxicity. Three systems satisfying the requirements for transparency (and so the particle size) were found but only two systems were used further for the solubilization of the photosenzitizers, the third one did not conform to the cytotoxicity tests. Another aim was to find, whether the photosensitizers, while solubilized using the selected systems, will not precipitate and will not be aggregated and therefore they would be usable in cell culture tests. Both the systems complying with the cytotoxicity tests proved to be usable. Photosenzitizers emulsified in them did not embody the aggregation or precipitation of the system. Finally measurements of the particles size of the systems with emulsified photosenzitizers were performed.
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Synthesis of quinoxalinoporphyrazines as potentially biologically active substances I.
Švec, Jaroslav ; Kopecký, Kamil (referee) ; Zimčík, Petr (advisor)
Title of diploma thesis: Synthesis of quinoxalinoporphyrazines as potentially active substances I Author: Jaroslav Švec The aim of my diploma thesis was synthesis of symmetrical octasubstituted zinc tetraquinoxalinoporphyrazine (TQP) with specific properties. In this work, 2,3-bis[2- (diethylamino)ethylsulfanyl]-quinoxaline-6,7-dicarbonitrile was chosen as the starting material. The synthesis of 2,3,11,12,20,21,29,30-Octakis[2-(diethylamino)ethylsulfanyl]tetra-[6,7]- quinoxalinoporphyrazine zinc(II) (ZnTQP) by the cyclization of precursor with zinc acetate in DMF failed. That is why, I prepared the magnesium complex of TQP first, then I obtained the metal-free TQP from it using acid (HCl). Incorporation of Zn ions into the center of TQP was accomplished by treatment of the metal-free derivative with zinc acetate. Finally, ZnTQP was treated with ethyliodide and the water soluble ZnTQP, with quaternary ammonium groups, was obtained. The new compounds were characterized by using standard spectral methods (UV-vis, IR, 1 H NMR, 13 C NMR, mass spectra, elemental analysis).
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Pyrazine derivatives as potential drugs III
Hošťálková, Anna ; Kopecký, Kamil (referee) ; Doležal, Martin (advisor)
Deriváty pyrazinu jako potanciální léčiva III. Tuberkulóza je problém v celosvětovém měřítku. Rostoucí počet nakažených lidí, vznik lékově rezistentních kmenů Mycobacterium tuberculosis a ko-infekce HIV vedly k naléhavé potřebě nových antituberkulotik. Tato diplomová práce referuje o současných léčivech používaných při léčbě tuberkulózy a některých nových potenciálních antituberkuloticích. Také bylo v rámci diplomové práce syntetizováno deset nových látek, derivátů anilidů kyseliny pyrazin-2-karboxylové, které byly charakterizovány jejich fyzikálními vlastnostmi a poté byla zkoušena jejich antimykobakteriální a antifungální aktivita in vitro. Abstract Pyrazine derivatives as potential drugs III. Tuberculosis is a health problem worldwide. The increasing number of infected people, emergence of drug resistant strains Mycobacterium tuberculosis and HIV co-infection have resulted in the urgent need for new antituberculosis drugs. This degree work reviews drugs used in current treatment for tuberculosis and some of new potential anti-tuberculosis drug candidates. Within the task of this work were also synthesized ten new compounds, derivatives of anilides of pyrazin-2-carboxylic acid, which were characterized by physical properties and then was assayed their antimycobacterial and antifungal activity in...
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Synthesis of bisquaternary nonsymmetric acetylcholinesterase reactivators
Sopr, Stanislav ; Kopecký, Kamil (referee) ; Doležal, Martin (advisor)
Stanislav Sopr: PREPARATION OF BISQUARTERNARY NON-SYMETRIC ACETYLCHOLINESTERASE REACTIVATORS Abstract The acetylcholinesterase (AChE) reactivators cause the re-activation of AChE activity after inhibition by organophosphorus compounds (OP). Such OP inhibitors were formerly developed as pesticides, but they were further used as chemical warfare agents due to their extremely high inhibition of cholinesterases. In this diploma thesis, 18 novel AChE reactivators were prepared. Their ability to reactivate paraoxon-inhibited AChE was evaluated in vitro via Ellman's method and compared to 3 standard commercial compounds (pralidoxime, obidoxime and HI-6). Any newly prepared compound was superior to known standards at 10-4 mol/l concentration. However, three novel compounds were able to exceed reactivation ability of known standards at 10-6 mol/l concentration and one novel compound exceeded reactivation limit for further potential in vivo evaluation.
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Pyrazine Derivates as Potential Antituberculotic Drugs
Kačírek, Michal ; Doležal, Martin (advisor) ; Kopecký, Kamil (referee)
Title of rigorous thesis: Pyrazine derivates as potential antituberculotic drugs Author: Mgr. Michal Kačírek In this rigorous thesis the recherche was realized which was focused on recent incidence of tuberculosis in the world, the possibility o f present therapy and the new trends in therapy as well. This thesis dealt with synthesis of undocumented compounds in literature. The starting compound was 5-chloro-6-methylpyrazine-2,3- dicabronitrile. The compounds were developed by aminodehalogenational reaction, linked to alkyl descriptor across amino group, whereas side chains were anal ogously extended. It can be said that the product was developed by reaction of 5 -chloro-6- methylpyrazine-2,3-dicabronitrile with corresponding primary aliphatic amine. Final compounds were characterized by thaw point, TLC, elementary analysis, 1 H a 13 C NMR and IR. All compounds were liable in vitro testing on their biological activity - antimycobacterial, antifungal and antibacterial. In the group of antituberculosis test ing the activity grew up from the least to the most lipophility compound.
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Synthesis of Pyrazincarboxylic Acid Derivates as Potential
Sedlák, Petr ; Doležal, Martin (advisor) ; Kopecký, Kamil (referee)
Title of diploma thesis: Synthesis of pyrazincarboxylic acid derivates as potential antituberculotics Tuberculosis is a disease with about 9 million new cases every year, about 1,7 million people are dying yearly. For several decades the same antituberculotics are used for treatment, but new strains of tuberculosis are appearing and resistance is growing. The old antituberculotics become to be ineffective. There is need to be new ones researched. Review of tuberculosis therapy and modern research were presented in this thesis. Nine novel derivates of acylamine pyrazinic acid and its esters were synthesized. Novel structures were characterized by melting points, TLC, IR, 1H and 13C NMR. This set was put through in vitro biological evaluation. Log P and Clog P were also calculated and were compared with novel synthesized structures.
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Solubilisation systems for potential photodynamic compounds IV.
Hlavinková, Petra ; Miletín, Miroslav (advisor) ; Kopecký, Kamil (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Drug Control Candidate: Petra Hlavinková Supervisor: PharmDr. Miroslav Miletín, Ph.D. Title of diploma thesis: Solubilisation systems for potential photodynamic compounds IV. The presented thesis deals with development and preparation of solubilisation systems for potentially photodynamically active substances. The aim was to determine the solubility of lipophilic photosensitizers of phthalocyanines azaanalogues type in several oils. MCT have been found suitable for ZIP21Zn and MUZ21Zn, and castor oil for P9Zn. These PS-in-oil solutions were incorporated into microemulsions using Cremophor® EL as the emulsifier. Molar extinction coefficients of photosenzitizers in selected oils were also measured. For photosenzitizer ZIP21Zn in MCT was found molar extinction coefficient 354400 l·mol-1 ·cm-1 at the wavelength of 653 nm; for MUZ21Zn in MCT was found the coefficient 416000 l·mol-1 ·cm-1 (746 nm), and for P9Zn in castor oil 352200 l·mol-1 ·cm-1 (703 nm). For selected solutions, prepared beforehand, the absorbance was determined and the concentration of photosenzitizers counted. At the MUZ21Zn and ZIP21Zn after conversion to microemulsions the absorbances in the microemulsions were also...
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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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Azaphthalocyanines as new structural group of fluorescence quencher.
Kopecký, Kamil ; Doležal, Martin (advisor) ; Lang, Kamil (referee) ; Pour, Milan (referee)
1 SUMMARY This dissertation thesis deals with searching of structurally new non-fluorescent quenchers of fluorescence, which may be used for preparation of molecular probes. These potential quenchers are derived from asymmetrically substituted alkylaminoderivatives of tetrapyrazinoporphyrazines - azaphthalocyanines. As the part of this work is preparation of precursors - 5,6-disubstituted pyrazine-2,3-dicarbonitriles. They are starting material for the preparation of final substances - tetrapyrazinoporphyrazines bearing different functional moieties. In total were prepared: 14 intermediates (3 of them have been described in our department) 13 final tetrapyrazinoporphyrazines (1 of them has been described in our department) 1 modified solid phase suitable for synthesis of marked oligonucleotides 2 by-products 23 undescribed compounds were prepared. Synthesis of 4 substances was not successful. Final products were tested for their singlet oxygen quantum yields, stability in solutions used for synthesis of oligonucleotides and subsequently ability of quenching of commercially available fluorofor Cy5® . This ability was compared with commercially available quencher Black Hole Quencher-2® . As a part of this work is confirmation of distribution of congeners arising during the statistical tetramerization of...
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