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Development of new pathways for syntheses of sesquiterpenoids
Topolovčan, Nikola ; Kotora, Martin (advisor) ; Dvořák, Dalimil (referee) ; Pour, Milan (referee)
This work consists of four consecutive parts, each dealing with syntheses of structurally diverse compounds. The syntheses were based on the methods within the domain of transition-metal catalyzed and/or mediated reactions with particular emaphasis on the application of organozirconium chemistry. 1. A method for synthesis of tricyclic condensed hydrocarbons possessing 5(6)-7-6(aryl) framework was developed. It is based on reaction of bicyclic zirconacyclopentenes, prepared by oxidative dimerization of enynes on a low-valent zirconocene species (Negishi's reagent), with ortho-halobenzaldehydes in the presence of various additives. The presence of two different centers of reactivity - the sp2 C-Zr and sp3 C-Zr bond - allowed sequential functionalization of each bond. Thanks to its higher nucleophilicity, the sp3 C-Zr bond reacted preferentially with the carbonyl carbon of the aldehyde yielding an oxazirconacycloheptene. The subsequent transmetallation of the remaining sp2 C-Zr bond with CuCl in the presence of other additives (catalysts) enabled an intramolecular cross-coupling reaction with the aryl halide moiety furnishing the desired tricyclic products in reasonable yields. The scope of the reaction with respect to differently functionalized reactants was assessed, as well as its mechanistic...
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Structural analysis of natural compounds with aliphatic branched chains using mass spectrometry
Strmeň, Timotej ; Cvačka, Josef (advisor) ; Kozlík, Petr (referee)
The diploma thesis focuses on analysis of fatty alcohols with mass spectrometry. Theoretical part describes distribution, main properties, usage and analytical methods for analysis of fatty alcohols. Experimental work focuses on the search for a proper derivatisation procedure for fatty alcohols, which would enable their detection with soft ionisation techniques of mass spectrometry, as well as their structural analysis. The main aim of the structural analysis is to find the methyl branching in the fragmentation spectra of derivatives of the fatty alcohols.
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Advanced glycation endproducts and their receptor (RAGE) in Alzheimer's disease
Štorkánová, Jesika ; Chlebek, Jakub (advisor) ; Opletal, Lubomír (referee)
Štorkánová, J.:Advanced glycation endproducts and their receptor RAGA IN Alzheimer's disease, Bachelor thesis, Charles University in Prague, Faculty of Pharmacy in Hradec Kralove, Department of Pharmaceutical Botany and Ecology, Hradec Kralove 2016, 97 p. Alzheimer's disease (AD) is the most common cause of dementia of late life. AD manifests as progressive memory impairment followed by a gradual decline in other cognitive abilities. For AD is characteristic the abnormal accumulation or aggregation of proteins. Advanced glycation endproducts (AGEs) are a heterogenous group of compounds that are formed when carbonyl group of reducing sugars reacts by a non-enzymatic reaction with amino acids in proteins, lipids and nucleic acids. The formation of AGEs promotes the deposition of proteins due to the protease resistant crosslinking, therefore is difficult to eliminace them from organism. AGEs can be detected in pathological deposits such as amyloid plaques and neurofibrillary tangles, which are prominent pathological feature sof AD. The formation of AGEs activate inflammatory signalling pathways, which are mediated by their receptor for advanced glycation endproducts (RAGE). RAGE is the signal transduction receptor which distinguishes a variety of signalling molecules including AGEs, β-amyloid, HMGB1...
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Use of kinase modulation in the Alzheimerʼs disease pathogenesis.
Polzerová, Iveta ; Chlebek, Jakub (advisor) ; Opletal, Lubomír (referee)
Polzerová, I: Use of kinase modulation in the Alzheimer's disease pathogenesis. Diploma thesis, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany and Ecology, Hradec Králové 2016, 91 p. Data used in this Diploma Thesis have been taken from foreigner scientific literary sources. It provides the summary of the not yet explored natural compounds from marine organisms with kinase inhibitory activity. The first chapter Alzheimer's disease describes a characteristic of the disease, its etiopathogenesis, risk factors and currently available treatment. At the beginning of the second chapter are mentioned new perspective approaches to treatment of Alzheimer's disease. Most of this chapter deals with kinases as potential therapeutic targets in the treatment of Alzheimer's disease. In the chapter, physiologic and pathophysiologic functions of GSK-3β and CK-1δ are described in the organism, and also, other kinases are mentioned which are involved in the pathogenesis of the disease. Next part dedicates analytical methods suitable for testing activity and inhibition of kinases in vitro and in silico, also deals with summary of the synthetic kinase inhibitors and characterizes an their properties. In this chapter is also described main part of this work - the...
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Natural products and their β-secretase inhibitory activity.
Kočová, Kateřina ; Chlebek, Jakub (advisor) ; Macáková, Kateřina (referee)
Kočová, K.: Natural compounds and their β-secretase inhibitory activity, Diploma thesis, Charles University in Prague, Faculty of Pharmacy in Hradci Králové, Department of Pharmaceutical Botany and Ecology, Hradec Králové 2015, 83 p. Data used in this Diploma Thesis have been taken from foreigner scientific literature. It provides the whole summary of natural compounds with β-secretase inhibitory activity. First chapter Alzheimer's disease briefly describes a definition, risk factors and symptomatology of the disease. Most of this chapter characterizes an etiopathology of the disease focused on amyloid theory. Finally there are also mentioned current approaches to therapy of Alzheimer's disease and those, which stay in clinical trials. Next part is dedicated to physiological functions and substrates of the β-secretase. This diploma thesis evaluates the current state of scientific research of synthetic inhibitors of β-secretase, describes the most important methods of testing inhibition and activity of β-secretase in vitro and outlines the issue of development of new inhibitors using in silico method. Main part of this work consists of the list of natural compounds with β- secretase inhibitory activity. This part is structured according to particular types of primary and secondary metabolites....
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Natural drugs in cancer treatment and their cytotoxicity
Hájková, Tereza ; Raudenská, Martina (referee) ; Provazník, Ivo (advisor)
The thesis deals with the natural substances in context with the cancer disease. The natural substances have a positive effect on the human organism and they are able to influence the viability and the growth of the cancer cells. The main mechanical device is to influence the mechanisms needed to start the apoptosis of the cancer cells and stopping further proliferation. The cancer cell lines utilization in the cancer disease is discussed in the thesis too. The thesis states common methods of determining the natural substances cytotoxicity. For the experimental part of the thesis it was chosen the MTT test method and the xCELLigence system for monitoring in real time. The mechanical device of the tested substance capsaicin in application on the prostate cell lines, tumorous PC3 and nontumorous PNT1A influence will be observed within the experimental part of the thesis.
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Evaluation of Extraction Curves Obtained by Supercritical Fluid Extraction from Plant Materials
Sovová, Helena
Evaluation of extraction curves is based on modelling the extraction process. Various models have been published and used to evaluate experimental data in the last years. A combined model, closely related to the results of ReverchonŽs research group, is presented in this study. Dimensionless form of the model is solved by numerical integration and also analytical approximative solutions are presented. Experimental extraction curves from the literature were analysed using the model for supercritical fluid extraction of both essential oils and fatty oils.
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