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Heterocyclic Compounds with Antimycobacterial Activity
Herzigová, Petra ; Klimešová, Věra (advisor) ; Potáček, Milan (referee) ; Pytela, Oldřich (referee)
The dissertation thesis belongs to the conception of the research of potential antimycobacterial compounds. The aim of this work is synthesis of sulphide pyridine derivatives and the relationship between structure and antimycobacterial activity. Within the framework of this Thesis, the 112 substituted derivates of 4-(subst. fenylalkylsulfanyl)pyridine-2-carboxylic acid were synthesized. Antimycobacterial activity of prepared substances has been tested under in vitro conditions against M. tuberculosis, and non-tuberculous mycobacteria M. avium and M. kansasii. The series of 4-(subst. phenethylsulfanyl)pyridine-2-carbothioamide (MIC 1-32 µmol/L) represents the most active substances (MIC 1-32 µmol/L). These derivates don't reach the activity used antituberculosis drugs against M. tuberculosis, but their activities against M. avium exceed that of isoniazid. The synthesis of new structures as potential antimycobacterial compounds forms the second part of Thesis. All synthesis is based on the use of bis- arylimidoyl chlorides of oxalic acid of as starting material. None of prepared new compounds don't display an interesting antimycobacterial activity.
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Development of capillary electrophoretic method for determination of phosphorylated components of bacterial cell membranes
Červinková, Jana ; Čabala, Radomír (advisor) ; Coufal, Pavel (referee)
Title: Development of capillary electrophoretic method for determination of phosphorylated components of bacterial cell membranes Author: Jana Červinková Department: Department of analytical chemistry Supervisor: RNDr. Radomír Čabala, Dr. Abstract: The bachelor work reviews the present state of knowledge of the analyses and determination of phosphorylated compounds present in the bacterial cell membranes. This group of compounds is represented mainly by phosphatidylglycerol, cardiolipine, and phosphatidylethanolamine and minority phosphatidylserine, phosphatidic acid and lysylphospatidylglycerol. Together with fatty acids these substances are the main components of cell membranes and they could be, to a certain degree, applied to either identification of bacteria or the study of bacterial behaviour at different conditions. Partially or fully non-aqueous capillary electrophoresis analytical method with spectrophotometric detection would be developed for their determination. Optimum experimental conditions for the separation of standards of selected compounds should be found within the framework of the bachelor thesis. Keywords: phosphorylated compounds, bacterial cytoplasmic membrane, capillary electrophoresis, thin layer chromatography, Bacillus subtilis.
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Influence of Cholestatic Liver Injury on the Elimination and Transport of Drugs
Brčáková, Eva ; Štaud, František (advisor) ; Tilšer, Ivan (referee) ; Lotková, Halka (referee)
The liver is a unique organ with a number of vital functions. Pivotal one is its participation on bile formation and secretion, import, detoxification and excretion of endogenous substances and xenobiotics. Bile formation is essential for both absorption of lipids in intestine and excretion of various endogenous compounds and xenobiotics (e.g. bile acids, bilirubin, cholesterol, phospholipids and drugs). This function is markedly impaired during extrahepatic and intrahepatic cholestasis with partial or complete stoppage of bile flow. Consequently, hepatic and further systemic accumulation of toxic biliary constituents, such as bile acids and bilirubin, occurs. In an effort to compensate this situation, spontaneous anti-cholestatic mechanisms are activated, which provide alternative excretory routes for toxic accumulating compounds (e.g. renal elimination of bile acids and xenobiotics into urine). These mechanisms include changes in the expression, localization and function of respective transporters in liver and kidneys. Another mechanism with a significant impact on bile formation and transport of compounds between bile and blood is blood-biliary barrier formed by connection of hepatocytes by "tight-junctions" and "gap-junctions". While "gap-junctions" exchange substances among cells,...
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Development of New Potential Antimycobacterial Active Agent Based on the Group of Salicylanilides
Monreal Férriz, Juana ; Vinšová, Jarmila (advisor) ; Opletalová, Veronika (referee) ; Polanc, Slovenko (referee)
Salicylanilides are an important class of aromatic compounds with a wide range of pharmacological activities, such as antibacterial, antifungal and anti-inflammatory, among others. Furthermore; several studies reported their potent antimycobacterial effect. Their activity results from multiple mechanisms. They are therefore interesting compounds for medicinal chemists. As phenolic- containing drugs, we hypothesised that a prodrug approach will make possible the improvement of the pharmaceutical, pharmacokinetic and/or pharmacodynamic properties of salicylanilides. This thesis describes the development of new potential antimycobacterial active agents based on this group that have shown interesting antimycobacterial activity against Mycobacterium tuberculosis, and some atypical strains. As the starting point for our research, the different strategies used in order to overcome the limited bioavailability of phenolic drugs were reviewed. Then new potentially antibacterial active prodrugs of salicylanilides, particularly N-benzyloxycarbonyl-ester and alkyl-carbamate derivatives of salicylanilide, active against M. tbc., MDR-TB strains or non-TB strains such as M. avium and M. kansasii, were prepared. Finally the physicochemical and pharmacokinetic properties of the most active synthesised compounds were...
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Application of Pd-Catalyzed Reactions to the Synthesis of Lactones
Šnajdr, Ivan ; Pour, Milan (advisor) ; Kotora, Martin (referee) ; Opletalová, Veronika (referee)
Within the framework of this Thesis, a method fot the preparation of 3,6- disubstituted pyranones was developed and 15 final lactones were synthesized, and their cytostatic and antifungal activity was investigated. Principal steps in the preparation of the compounds were Yamaguchi-Hirao alkylation, hydroalumination followed by iodation and Pd- catalyzed carbonylative lactonization. None of the target compounds displayed interesting cytostatic or antifungal activity (IC50 < 10 μmol/L), which was suprising given the significant antifungal activity of analogous butenolides. The development of the synthesis of 3- monosubstituted pyranones is described next. Our strategy is based on the use of 5,6-dihydro-2H- pyran-2-one as the starting material, which was converted into the 3-iodo-5,6-dihydro-2H- pyran-2-one in one step. The key step of the synthesis was Pd-catalyzed Suzuki coupling. Finally, the preparation of α- and β-substituted-γ-alkylidenepentenolides is described. The target compounds exhibited significant cytostatic activity (IC50 < 5 μmol/L) against all tested tumor cells (CCRF-CEM, HeLa S3, HT 29, HL 60, L 1210).
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Flame retardants and their penetration into the terrestrial ecosystem
Chytil, Václav ; Čáslavský, Josef (referee) ; Vávrová, Milada (advisor)
This diploma thesis was focused on the analysis of four compounds from brominated flame retardants group, namely pentabromoethylbenzene, hexabromocyclododecane, hexabromobenzene and tetrabromobisphenol A. Matrices were represented by four soil samples and four seat of fire samples. In addition, bisphenol A was also determined. First of all, process of extraction of analytes from matrices was optimized. Three different extraction techniques were tested (pressurized solvent extraction, microwave-assisted extraction and ultrasound-assisted extraction). Next step was to verify stability of target compounds in strongly acidic conditions and to optimize clean-up of extract by column chromatography. Gas chromatography with electron capture detection (GC-ECD) was chosen as an appropriate analytical method for the determination of brominated flame retardants. Bisphenol A was determined by gas chromatography with mass spectrometric detection (GC-MS). The derivatization of phenolic analytes before their final analytical determination was also essential.
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The chosen validation parameters of method for assessment of aroma compounds in processed cheese analogues
Burdějová, Lenka ; Horváthová, Viera (referee) ; Vítová, Eva (advisor)
This Bachelor‘s thesis deals with the issues of method validation for assessment of aroma compounds in processed cheese analogues. The method is based on the isolation of volatiles from the sample using Solid Phase Microextraction (SPME) and their subsequent determination by gas chromatography. The theoretical part focuses on general characteristics, classification and producing technology of processed cheese analogues. Further, aroma active substances contained in cheese analogues, differences from the classic processed cheese and processed cheese analogues occurring on the Czech market are mentioned. The methods for determination of aroma active compounds with a focus on Solid Phase Microextraction and gas chromatography are briefly mentioned. Within experimental part of the work the linearity and repeatability of the SPME-GC method were verified and detection limits and limits of quantification of selected standards were determined. Then the method was applied to chosen samples of processed cheese analogues with addition of different types of vegetable fats.
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The chosen validation parameters of method for assessment of aroma compounds in elderberries
Christovová, Silvia ; Ürgeová, Eva (referee) ; Vítová, Eva (advisor)
This bachelor thesis deals with the assessment of aroma active compounds in elderberries (Sambucus nigra L.). In the theoretical part the chemical composition and attributes of elderberries are described. Brief information on their healing properties is also given. The possible processing methods in food industry, as well as the traditional means of use at home, are discussed furthermore. Following chapters describe the gas chromatography method combined with the technique of solid-phase microextraction, utilized for the specification of aroma active compounds. The validation of this method is also included. The aim of the experimental part of the work was to verify a set of the selected validation parameters of the SPME-GC method, specifically linearity, the limits of detection (LOD), the limits of quantification (LOQ) and repeatability. Subsequently, the SPME-GC method was applied on the chosen elderberry juice samples. In total, 37 different volatile aroma active compounds were identified and quantified, 15 of which belonged to alcohols, 9 to aldehydes, 5 to ketones, 5 to esters and 2 other compounds. The chemical composition of individual samples was not uniform; no single sample contained all of the identified compounds.
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