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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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Conjugate Addition Coupled with Enolate Oxidation in the Total Synthesis of Natural Polyphenols
Mašek, Tomáš ; Jahn, Ullrich (advisor) ; Pospíšil, Jiří (referee) ; Švenda, Jakub (referee)
1 ABSTRACT This thesis describes the development of the concept of C-C bond forming conjugate addition/oxidative cyclisation reactions and their application in the total synthesis of natural polyphenols. The first part deals with the development of methodology for conjugate addition of main- group organometallic reagents to unsaturated carbonyl compounds coupled with in situ single electron transfer oxidation. The resulting radical undergoes stereoselective cyclisation, that can be followed by a second SET oxidation, leading to further cationic cyclisation. This methodology is ideally suited for the synthesis of furoindane stilbenolignans (FIS), a neglected and structurally distinct class of natural polyphenols. Using this process, racemic synthesis of a derivative of kompasinol A was achieved, confirming the relative configuration of FISs. In an effort to develop asymmetric route to FISs, an unprecedented direct conjugate addition of aryllithiums to ylidenemalonates mediated by diethers and diamines was discovered, leading to asymmetric synthesis of gnetifolin F and 11- deoxykompasinol A. Based on X-ray evidence, a related annulation methodology consisting of direct conjugate addition/epoxide opening was shown to result in bridged lactones, instead of isomeric FISs. This finding led to an approach for the...
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Use of natural resources in elementary school education
KLIMEŠOVÁ, Hana
This diploma thesis "The use of natural materials in teaching at the 1st stage of primary school" deals with the use of natural material in primary school and science, their use in interdisciplinary relationships. The work is conducted not only as worksheets for students, but also interesting didactic sheets for teachers to diversify teaching and support activites for students during the acquisition. Thanks to its easy availability, natural material is a popular material for research and use in teaching. Pupils like to experiment, find out and get to know the material. They learn nonviolently and form a positive relationship with nature. Experimentation and research can take place in the form of project-based teaching, which also develops relationships between students and supports independent thinking. The activities and activities contained in the work can be used by teachers in project or group teaching, they can bet the basis for projects focused on the use of natural materials in science and elementary school lessons. The activities are designed to take advantage of interdisciplinary relationships and are based on the expected outputs of the Framework Educational Program for Basic Education. The diploma thesis consists of two parts. The first part deals with theoretical knowledge, the second part is devoted to the practical part.
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Synthesis of selagibenzophenone C and derivatives for confirmation of the stucture of the natural product.
Kunák, Dominik ; Rýček, Lukáš (advisor) ; Matoušová, Eliška (referee)
5 Abstract This bachelor's thesis deals with the preparation of selagibenzophenone C. The natural product was prepared in a six-step synthesis, where subsequent analysis and comparison of the spectrum of the synthetic substance with the spectra described for the isolated product verified whether the structure of the isolated natural product was deciphered correctly. Furthermore, it was verified that intermediates in the synthesis of selagibenzophenone C can undergo cyclization reactions to form a fluorene core. Analogous cyclization is the main step in the biosynthesis of selaginpulvilins from the corresponding selaginellins. The obtained fluorene derivatives will therefore be used as standards in the following studies to determine whether these substances obtained by us are also natural compounds. Key words Total synthesis, natural product, polyphenols, natural fluorene derivates, selagibenzophenones
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Using tandem cyclisation/Sonogashira cross-coupling in the synthesis of natural products and their derivatives
Liška, Benno ; Matoušová, Eliška (advisor) ; Míšek, Jiří (referee)
The subject of this bachelor's thesis is the preparation of polycyclic compounds using the tandem cyclisation/Sonogashira cross-coupling and a potential application of this reaction to the synthesis of natural products and their derivatives. The aim was to study this method using nonaromatic starting materials with a six-membered ring and to explore possibilities for functionalisation of the triple bond of the newly prepared compounds. The first part of this thesis deals with the synthesis of starting materials containing either an ether group or a malonate residue. The second part deals with the optimisation of conditions and the investigation of the scope of Heck reaction and Sonogashira cross-coupling. The third part describes the attempts to hydrate the triple bond and the last part contains reactions with allylic alcohols. Keywords: synthesis, tandem reaction, natural products, Sonogashira cross-coupling, Heck reaction
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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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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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Asymmetric Tandem Lithium Amide Conjugate Addition/Radical Reactions and Their Application in the Total Synthesis of Natural Products
Hidasová, Denisa ; Jahn, Ullrich (advisor) ; Kočovský, Pavel (referee) ; Míšek, Jiří (referee)
This thesis deals with single-electron transfer (SET) radical processes mediated by ferrocenium hexafluorophosphate and TEMPO and their application in the total synthesis of natural products. Asymmetric aminooxygenation methodology for the synthesis of anti-β-amino-α-hydroxy acid derivatives has been developed by utilizing a highly diastereoselective aza-Michael addition of chiral lithium amides to various α,β-unsaturated esters or amides/SET oxidation/radical α-oxygenation. The potential of this methodology was demonstrated in short total syntheses of the anti-β-amino-α-hydroxy acid fragments of the macrocyclic (depsi)peptides perthamide C and largamide H, and (-)-cytoxazone, which is a selective modulator of TH2 cytokine secretion. The SET-catalyzed asymmetric tandem lithium amide conjugate addition/5-exo radical cyclization/oxygenation reactions were applied in the synthesis of highly substituted pyrrolidines, azabicyclo[n.3.0]alkanes and spiropyrrolidines. An enantioselective total synthesis of the pyrrolidine alkaloid (-)-α-kainic acid was accomplished by employing the SET-catalyzed 5-exo radical cyclization/oxygenation.
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