|
|
Novel synthetic approaches toward non-peripherally substituted phthalocyanines
Kočiščáková, Lucia ; Zimčík, Petr (advisor) ; Kučerová, Marta (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Candidate Lucia Kočiščáková Supervisor Doc. PharmDr. Petr Zimčík, PhD. Title of Thesis Novel Synthetic Approaches Toward Non-Peripherally Substituted Phthalocyanines Phthalocyanines are macrocyclic compounds structurally related to porphyrins, which are used as photosensitizers in photodynamic therapy in the treatment of tumor diseases. The principle of photodynamic therapy is based on activation of photosensitizer by specific wave lenght of light (in the area of visible spectrum), that is absorbed by photosensitizer. The excited photosensitizer releases the absorbed energy by generation of reactive molecule of singlet oxygen that causes damage to cancer cells. In my diploma thesis, we synthesized precursors for phthalocyanines, derivates of phthalonitrile. I was focused on the 3,6-disubstitued phthalonitriles because with the non- peripheral substitution of the final phthalocyanines leads to better, such as significant red shift of the main absorption band. We chose nucleophilic substitution and Buchwald-Hartwig coupling as the main synthetic approaches and we compared different reaction conditions to optimize them.
|
|
|
Oxadiazoles as potential drugs II.
Kolčárková, Lucie ; Kučerová, Marta (advisor) ; Zimčík, Petr (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Candidate: Kolčárková Lucie Supervisor: PharmDr. Marta Kučerová, Ph.D. Title of diploma thesis: Oxadiazoles as Potential Drugs II. My work was focused on finding new potential drugs with antibacterial and antifungal activity, from the reason of increasing microbial resistance against current drugs. 3-Pyrazin-2-yl-1,2,4-oxadiazole was chosen as the structural scaffold for the research. In the theoretical part of this diploma thesis I have reviewed various procedures of the preparation of 1,2,4-oxadiazoles. The methods of preparation have been assorted according to the starting material used. In the experimental part of this study several different ways of preparation to synthesize these compounds were explored and then improvement of reaction conditions in order to gain the pure product in good yields were tested. None of compounds has been reported so far. They have been characterized by IR and NMR spectra and by melting points as well. Their purity was checked by TLC and elemental analysis. Six of the synthesized compounds have been tested in vitro for their antibacterial and antifungal activity. One of the compounds has shown medium antifungal activity and another one has...
|
|
|
Sulfonated azaphthalocyanines - synthesis and evaluation of their photodynamic activity
Jančárová, Alena ; Zimčík, Petr (advisor) ; Doležal, Martin (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Author: Alena Jančárová Supervisor: doc. PharmDr. Petr Zimčík, Ph.D. Co-supervisor: RNDr. Miloslav Macháček, Ph.D. Title of diploma thesis: Sulfonated azaphthalocyanines - synthesis and evaluation of their photodynamic activity Photodynamic therapy is one of the methods used for destruction of undesirable cells. It combines three essentially nontoxic components: light, oxygen and a photosensitizer. Azaphthalocyanines (AzaPcs) are promising compounds with photosensitizing properties. However, their major disadvantage is their low water solubility and significant aggregation that decreases their photodynamic activity. The aim of this work was to synthesize an anionic derivative of AzaPc substituted with sulfonic groups on periphery characterized by good solubility in water and to evaluate its photodynamic properties. The first step in the synthesis was condensation of diaminomaleonitrile with benzil giving 5,6-diphenylpyrazine-2,3-dicarbonitrile. Subsequently, the cyclotetramerisation with zinc acetate in 2-dimethylaminoethanol as a solvent was performed. The final product was obtained by sulfonation with chlorosulfonic acid followed by hydrolysis with sodium hydrogen carbonate....
|
|
|
Compounds combining pyrazinamide and 4-aminobenzoic acid fragments as potential antituberculars
Žecová, Jana ; Zitko, Jan (advisor) ; Zimčík, Petr (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical chemistry and Pharmaceutical analysis Author: Jana Žecová Supervisor: PharmDr. Jan Zitko, Ph.D. Title of diploma thesis: Compounds combining pyrazinamide and 4-aminobenzoic acid fragments as potential antituberculars Tuberculosis is a severe infectious disease, which has been afflicting the human world population for centuries. It's figuring in the scale of the deadliest diseases as well as the occurring of strains resistant to therapy requires a serious approach to this problem and the research of new therapeutic means. Among the actual antituberculars figure two compounds, PZA and PAS. Pyrazinamide is a first line drug, and its derivatives are subject of the research in the Department of Pharmaceutical chemistry and Pharmaceutical analysis. Structurally similar to 4-aminobenzoic acid, PAS is a second line antitubercular, which is again actual in the therapy of resistant form of TBC. This diploma thesis treats about possibilities of the use of compounds combining fragments of PZA and 4-aminobenzoic acid as potential antituberculars. Furthermore, this thesis evaluates the influence of PAS fragment in the derivatives prepared with this antimycobacterial purpose. The theoretical part describes the actual state of...
|
|
|
Synthesis of phenol-substituted azaphthalocyanines as fluorescent pH sensors
Valer, Vojtěch ; Zimčík, Petr (advisor) ; Miletín, Miroslav (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department Department of Pharmaceutical Chemistry and Drug Control Candidate Vojtěch Valer Supervisor Doc. PharmDr. Petr Zimčík, Ph.D. Title of Thesis Synthesis of phenol-substituted azaphthalocyanines as fluorescent pH sensors Azaphtalocyanines (AzaPc) bearing suitable phenol moieties were found to be potentially useful pH sensors. In this study, we focused on expanding the series of phenol derivatives synthesized previously. The main reason of our effort was the fact, that pKa of the previous compounds (12.5-12.7) did not fall into physiologically useful range. Two different strategies to synthesis of precursors were developed. Synthesis of the precursor with two phenols started by benzoin condensation of p-anisaldehyde to obtain corresponding acyloin, which was oxidized to diketone and dealkylated. Subsequently, the substituted pyrazine was obtained by condensation of this diketone with diaminomaleonitrile (DAMN). Synthesis of precursor with one phenol began with oxidation of 4- hydroxyacetophenone to corresponding ketoaldehyde, which was used in condensation with DAMN to the pyrazine. The mixed cyclotetramerization of mono or disubstituted pyrazine with 5,6-bis(tert- butylsulfanyl)pyrazine-2,3-dicarbonitrile provided the mix of congeners...
|
|
|
Synthesis and study of photophysical and photochemical properties of phthalocyanines and azaphthalocyanines
Váchová, Lenka ; Zimčík, Petr (advisor) ; Doležal, Martin (referee) ; Imramovský, Aleš (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Candidate: Mgr. Lenka Váchová Supervisor: doc. PharmDr. Petr Zimčík, Ph.D. Title of the doctoral thesis:Synthesis and study of photophysical and photochemical properties of phthalocyanines and azaphthalocyanines Phthalocyanines (Pc) and their aza-analogs azaphthalocyanines (AzaPc) are planar macrocyclic complexes derived from porphyrins with a significant absorption band in the range 620-800 nm. Due to their unique photophysical and photochemical properties, together with the high variability of macrocycle substitution, they are important representatives in the modern concepts of materials, industry, electrotechnics and medicine. They are used as photosensitizers in photodynamic therapy of cancerous and non-malignant diseases, fluorescence quenchers for molecular probe labeling in biology or drug and gene delivery agents in cellular environment. The effect of Pc and AzaPc is influenced by their structure, mainly by the character of peripheral substituents, the central chelated metal and the type of the macrocycle. In the first part of the thesis, the influence of intramolecular charge transfer (ICT) on the series of unsymmetrical tetrapyrazinoporphyrazines and...
|
|
|
Inhibitors of mitochondrial enzymes as potential therapeutics for Alzheimer's disease
Hroch, Lukáš ; Musílek, Kamil (advisor) ; Farsa, Oldřich (referee) ; Zimčík, Petr (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Department of Pharmaceutical Chemistry and Drug Control Candidate Mgr. Lukáš Hroch Supervisor assoc. prof. PharmDr. Kamil Musílek, Ph.D. Title of Doctoral Thesis Inhibitors of mitochondrial enzymes as potential therapeutics for Alzheimer's disease There were about 50 million people living with dementia in 2015. It is expected that number of people living with dementia will reach 130 million by the year of 2050. Alzheimer's disease (AD) is one of the most common causes of dementia and it is estimated to account for about 60 80% of overall cases. Current symptomatic treatment only alleviates symptoms and delays progression of the disease. However, there is no effective treatment, which would address the underlying cause of AD. The extracellular depositions of insoluble amyloid beta peptide (Aβ) were thought to be a causative factor and main target for a long time. Yet, targeted treatment towards the reduction of extracellular Aβ depositions failed to show expected therapeutic merit. Later on, it has been shown that development of AD starts much earlier than any Aβ plaques or symptoms could be observed. With growing evidence of soluble Aβ in intracellular regions, main attention moved to investigations of Aβ within the cells. Aβ...
|
|
|
Synthesis of cationic phthalocyanines
Cidlina, Antonín ; Zimčík, Petr (advisor) ; Miletín, Miroslav (referee)
CHARLES UNIVERSITY IN PRAGUE FACULTY OF PHARMACY IN HRADEC KRÁLOVÉ DEPARTMENT OF PHARMACEUTICAL CHEMISTRY AND DRUG CONTROL Author: Antonín Cidlina Supervisor: Assoc. Prof. PharmDr. Petr Zimčík PhD. Title: Synthesis of cationic phthalocyanines In my thesis, I dealt with the preparation of cationic phthalocyanines containing quaternary ammonium groups in peripheral chains that are attached to α or β positions of the macrocycle. The synthesis of precursors for cyclotetramerization was the first step of this work. They were prepared by nucleophilic substitution of aromatic dicarbonitriles by 2- (diethylamino)ethanthiolate. These precursors were used to cyclotetramerization in presence of magnesium butoxide. Magnesium phthalocyanines were prepared by this procedure. Magnesium complexes were converted to metal-free phthalocyanines in acidic medium. Then, they reacted with anhydrous zinc acetate to form zinc phthalocyanines. Subsequently, alkylation of peripheral amino groups by ethyliodide led to quaternized Pc. In addition, the derivates with substitution in α positions did not aggregate in aqueous media. Furthermore, zinc phtalocyanine substituted in α positions had very good photochemical properties. That is why it may become potential photosensitizer with promising photodynamic activity.
|
|
|
Syntheses of azaphthalocyanine fluorescence sensors with the improved selectivity towards desired metal cations
Uhlířová, Štěpánka ; Nováková, Veronika (advisor) ; Zimčík, Petr (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department Department of Biophysics and Physical Chemistry Candidate Štěpánka Uhlířová Supervisor doc. PharmDr. Veronika Nováková, Ph.D. Title of thesis Syntheses of azaphthalocyanine fluorescence sensors with the improved selectivity towards desired metal cations Azaphthalocyanines (AzaPc) bearing aza-crowns on the periphery may be used as fluorescence sensors for metal cations. Emission in the red part of the spectrum is a great advantage of these compounds because such light is not absorbed by endogenous chromophores. Previous projects served mostly as a proof of concept where sensitivity of AzaPc sensors to a series of alkali and alkaline earth metal cations was shown. The aim of this diploma thesis is focused on the improvement the selectivity of a recognition moiety for particular cations. This can be achieved by the attachment of lariat ethers or crown ethers close to aza-crown moiety. Firstly, appropriate precursors, i.e. 5,6-disubstituted pyrazine-2,3-dicarbonitriles, were prepared by nucleophilic substitution. Then, cyclotetramerization of two different precursors (A and B) using a template method with zinc acetate in a high boiling solvent provided a statistical mixture of AzaPc congeners. Desired unsymmetrical AzaPc of ABBB type was...
|
|
|
Synthesis and study of photophysical and photochemical properties of phthalocyanines and azaphthalocyanines
Váchová, Lenka ; Zimčík, Petr (advisor) ; Doležal, Martin (referee) ; Imramovský, Aleš (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Candidate: Mgr. Lenka Váchová Supervisor: doc. PharmDr. Petr Zimčík, Ph.D. Title of the doctoral thesis:Synthesis and study of photophysical and photochemical properties of phthalocyanines and azaphthalocyanines Phthalocyanines (Pc) and their aza-analogs azaphthalocyanines (AzaPc) are planar macrocyclic complexes derived from porphyrins with a significant absorption band in the range 620-800 nm. Due to their unique photophysical and photochemical properties, together with the high variability of macrocycle substitution, they are important representatives in the modern concepts of materials, industry, electrotechnics and medicine. They are used as photosensitizers in photodynamic therapy of cancerous and non-malignant diseases, fluorescence quenchers for molecular probe labeling in biology or drug and gene delivery agents in cellular environment. The effect of Pc and AzaPc is influenced by their structure, mainly by the character of peripheral substituents, the central chelated metal and the type of the macrocycle. In the first part of the thesis, the influence of intramolecular charge transfer (ICT) on the series of unsymmetrical tetrapyrazinoporphyrazines and...
|
guest ::
RSS feed.