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Miniaturized and fast method for solubility and level of supersaturation determinations of drug nanocrystals
Paľová, Romana ; Nováková, Veronika (advisor) ; Kuchařová, Monika (referee)
Title of thesis: Miniaturized and fast method for solubility and level of supersaturation determinations of drug nanocrystals Author: Romana Paľová Department: Biophysics and Physical Chemistry Supervisor: Doc. Veronika Nováková, Ph.D. Specialized supervisor: Assoc. Prof. Leena Peltonen, Ph.D. As a formulation strategy for improving the bioavailability of poorly water-soluble drugs, drug nanocrystals can be employed. Several studies have shown that drug nanocrystals exhibit higher dissolution rate compared to conventional drug formulations. However, when orally administered, various conditions in gastrointestinal tract, such as changes in pH may result in problematic absorption. In this work, the preparation of drug nanosuspension of itraconazole (ITZ), as model poorly water-soluble compound, was carried out. The nanosuspension was prepared by using wet milling method of preparation, with suitable stabilizers added (Poloxamer 407 and Hydroxypropyl methylcellulose). Hydrochloric acid buffer pH 1.2 was chosen to create an environment similar to gastric fluids. In order to investigate changes in solubility of ITZ nanosuspension, UV spectrophotometer was used. Measurement was performed at the wavelength 551 nm, where dissolved ITZ does not absorb light and no change in absorbance occurred....
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Benzodiazines as compounds with potential bronchodilatory effect
Ježková, Věra ; Špulák, Marcel (advisor) ; Nováková, Veronika (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Inorganic and Organic Chemistry Candidate: Věra Ježková Consultant: PharmDr. Marcel Špulák, PhD. Title of Thesis: Benzodiazines as compounds with potential bronchodilatory effect The most active compounds from previous screening contained (piperidine-1-yl)propyl moiety attached to quinazoline or quinoxaline rings. The goal of this project was to introduce hydroxyl into the three-membered carbon linker with a possibility of further modification. The synthesis was carried out employing the reaction of commercially available quinazolinone and racemic epichlorohydrin leading to epoxide which undergoes nucleophilic attack resulting in hydroxyquinazolinones. Similarly, this reaction sequence was applied on quinoxalinone. However, the attempts with sulphur analogue of quinazolinone and quinoxalinone failed. All prepared compounds have been evaluated for their bronchodilatory activity. The results indicated similar level of bronchodilatory effect as their precursors, except one with cyclohexylamine ring, which showed higher bronchodilatory effect.
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Synthesis of low-symmetry azaphthalocyanine for the labeling of DNA probes increasing the susceptibility of the molecular-biological methods
Schimmerová, Aneta ; Nováková, Veronika (advisor) ; Miletín, Miroslav (referee)
1. ABSTRACT Charles University, Faculty of Pharmacy in Hradec Králové Department Department od Biophysics and Physical Chemistry Student Aneta Schimmerová Supervisor Assoc. Prof. PharmDr. Veronika Nováková, Ph.D. Title of thesis Synthesis of low-symmetry azaphthalocyanine for the labeling of DNA probes increasing the susceptibility of the molecular- biological methods Azaphthalocyanines (AzaPc) are planar macrocyclic compounds. The alkylamino substituted derivatives can be used as dark quenchers in DNA-hybridization assays. A probe usually contains a quencher and a fluorophore. If these two moieties are close enough, the emitted fluorescence is quenched by the quencher. After the hydrolysis of the oligonucleotide probe, the fluorescence appears because of the long distance between the quencher and fluorophore. Thanks to the large system of conjugated double bounds, AzaPc absorb over a wide range of wavelengths from 300 nm to 750 nm. Such absorption covers all fluorophores used in hybridization assays nowadays, thus AzaPc may serve as universal dark quenchers. The aim of this study was to prepare an AzaPc, that will be possible to attach inside an oligonucleotide strand. Furthermore, a planar moiety bounded to AzaPc will intercalate into DNA and improve the strength of binding of the probe to DNA. First, the...
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Determination of fatty acids in human tissues
Turňová, Ivana ; Kuchařová, Monika (advisor) ; Nováková, Veronika (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biophysics and Physical Chemistry Candidate: Ivana Turňová Supervisor of Diploma Thesis: Mgr. Monika Kuchařová, Ph.D. Consultant: prof. MUDr. Zdeněk Zadák, CSc. Title of Diploma Thesis: Determination of fatty acids in human tissues The fatty acids are non-negligible component of lipids as one of the basic nutrients. This thesis in its theoretical part presents above all the group of polyunsaturated fatty acids (PUFA), which are important structural units of the cell membranes, they are also the precursors to several significant biologically active substances. In the human organism PUFA participate in many physiological and pathological processes this way, where they cause the large spectrum of actions. Onwards the thesis describes the gas chromatography method that is used in chemical analysis of lipids for the fatty acid determination as the gold standard. Experimentally, the fatty acid representation was determined in the blood, muscle, heart, liver and kidney among 26 cadavers divided into two groups according to the presence/absence of inflammatory process at the time of death. The data obtained were statistically analysed. The results were descriptively evaluated and there were indicated possible explanations of differences...
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Determination of Lipophilicity of Potential Drugs
Coufalová, Iva ; Kubíček, Vladimír (advisor) ; Nováková, Veronika (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Drug Control Author: Mgr. Iva Coufalová Consultant: Ing. Vladimír Kubíček, CSc. Thesis Title: Determination of Lipophilicity of Potential Drugs This rigorous thesis deals with the determination of lipophilicity of new synthesized potential drugs based on pyrazine structure by reversed phase high performance liquid chromatography. The theoretical part contains a brief overview of the drugs development and clinical studies, there are also summarized historical and currently common used processes for lipophilicity estimating, including the basic principles of chromatography. Another part of thesis is engaged in to the measurement of specific samples of drugs on a Zorbax ECLIPSE XDB-C8 600 Bar, 50.0x3.0 mm, 1.8 µm column. This column was chosen in order to shorten the retention times of the measured samples compared with C18 column packing. For the lipophilicity values of the examined drugs are considered the logarithm of capacity factor values which were determined by extrapolation to zero concentration of methanol in the mobile phase. In conclusion there was made a comparison of the results with the values previously obtained on a Zorbax ECLIPSE XDB-C18 600Bar, 50.0x4.6 mm, 1.8 μm column and...
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The effect of substitution on the basicity of azomethine nitrogens of phthalocyanines
Ludvová, Lucie ; Nováková, Veronika (advisor) ; Miletín, Miroslav (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department: Department of Pharmaceutical Chemistry and Drug Control Candidate: Mgr. Lucie Ludvová Supervisor: assoc. prof. PharmDr. Veronika Nováková, Ph.D. Title of Thesis: The effect of substitution on the basicity of azomethine nitrogens of phthalocyanines This work deals with the effect of substituents on the basicity of azomethine nitrogens in phthalocyanines, which are macrocyclic compounds with wide system of conjugation bounds. Substituents differed in their position at the macrocycle (attached at peripheral or non-peripheral positions) and in the type of substituents (alkylsulfanyl-, alkyloxy- or alkyl groups). Three zinc phthalocyanines were prepared in this project to complete the above mentioned series. In the first step, appropriate precursors were prepared by multi-step procedure using e.g. nucleophilic substitution or Negishi coupling reaction. These precursors were further used for cyclotetramerization reaction to get metal free phthalocyanines. Finally, the zinc cation was coordinated into the center of phthalocyanines. The second part of the project focused on the determination of the basicity of this series of zinc phthalocyanines by the mean of the absorption spectroscopy. The highest basicity showed...
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The impaired change in plasma long-chain acylcarnitine level as a marker of insulin resistence
Šišmová, Petra ; Nováková, Veronika (advisor) ; Čečková, Martina (referee)
Charles University Faculty of Pharmacy in Hradec Kralove Department of Biophysics and Physical Chemistry Rīga Stradiņš University Latvian Institute of Organic Synthesis Laboratory of Pharmaceutical Pharmacology Candidate: Petra Šišmová Supervisor: Dr. Pharm. Elina Makarova, assoc. prof. Veronika Nováková, Ph.D. Title of the diploma thesis: The impaired change in plasma long-chain acylcarnitine level as a marker of insulin resistance Insulin resistance presents one of the factors that could lead to type 2 diabetes mellitus (T2DM). Increased levels of long-chain (LC)-acylcarnitines are associated with obesity and T2DM and recent studies suggest that LC-acylcarnitines could play a role in the development of insulin resistance. Early diagnosis of insulin resistance would help to prevent the onset of T2DM and the development of associated complications. The purpose of this study was to determine whether the measurements of the changes in acylcarnitine concentrations during the glucose tolerance test (GTT) could be used as a novel marker of insulin resistance. After intraperitoneal administration of glucose in high fat diet (HFD)-fed C57bl/6N, db/db mice and respective controls the concentrations of glucose, insulin, glycated haemoglobin, free fatty acids (FFAs) and acylcarnitine levels in the fasted...
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Study of recognition moieties of sensoric azaphthalocyanines
Lochman, Lukáš ; Nováková, Veronika (advisor) ; Musílek, Kamil (referee) ; Kubát, Pavel (referee)
Charles University, Faculty of Pharmacy in Hradec Kralove Department: Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Author: Mgr. Lukas Lochman Supervisor: Doc. PharmDr. Veronika Novakova, Ph.D. Advisor: Doc. PharmDr. Petr Zimcik, Ph.D. Doctoral Thesis: Study of recognition moieties of sensoric azaphthalocyanines Azaphthalocyanines (AzaPcs) are planar macrocyclic compounds with unique photophysical properties like absorption and emission over 650 nm and high quantum yields of fluorescence. Alkylamine substituted AzaPcs have been shown to undergo an ultrafast intramolecular charge transfer (ICT) which is responsible for efficient quenching of excited states (nonfluorescent OFF state). ICT occurs between donor (peripheral amine) and acceptor (macrocyclic core). Blocking of ICT leads to restoration of high fluorescence emission (fluorescent ON state) which is the competitive relaxation pathway. There are two known possible ways how to block ICT in AzaPcs sofar: By protonation of donor in pH sensitive AzaPc sensors or by coordination of metal cation into the recognition moiety resulting in cation sensitive AzaPc sensors. Above-mentioned properties predestinate AzaPcs to become new fluorescent sensors with good brightness and advantageous absorption and emission of red light deep...
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