Rigorous theses

Rigorous theses 15,322 records found  beginprevious7421 - 7430nextend  jump to record: Search took 0.00 seconds. 
The application of high-efficiency separation methods for chiral and achiral separations
Šubová, Martina
In the first part of the doctoral thesis, the capillary electrophoresis was used to test the potential chiral separation properties of monosubstituted cyclodextrin derivatives, namely PEMEDA- and PEMPDA-β-cyclodextrins for the group of selected analytes. Both selectors exhibited excellent enantioseparation properties for N-boc-D,L-tryptophan, where the enantiomers were completely separated even at 0.5 mmol·l-1 concentration of the cyclodextrin derivative in the background electrolyte. However, the differences between the enantiodiscrimination properties of individual derivatives were minimal. The second test group consisted of two cyclodextrin derivatives, namely 2-O- and 3-O- cinnamyl-α-cyclodextrins. These derivatives are able to form supramolecular polymers in aqueous solutions that disintegrate at elevated temperature. The formation of these polymers was tested by NMR and DLS experiments. None of the tested cyclodextrin derivatives showed enantiodiscrimination properties towards a group of selected analytes. In the frame of antipredatory study, HPLC-MS/MS method working in HILIC mode was used for separation of ten pterin derivatives and riboflavin, which can be present as pigments in insects, reptiles or amphibians as a part of their warning coloration. The developed methodology was applied for...
Polymeric nanofibrous carriers for local application of hydrophobic drugs - studying of the drug release profiles by HPLC
Hampejsová, Zuzana
Immunosupresive and cytostatic drugs have many serious side effects which are dose dependent. Local application of drugs prolongs and increases the concentration of drug in the target place and, therefore, may reduce their serious side effects. Polymeric fiber carrier could be used as drug delivery system for local application. Polylactide (PLA) micro/nanofibers containing hydrophobic drugs (immunosupresive drug cyclosporine A and cytostatic drug paclitaxel) were prepared to study this potential medicinal application. Poly(ethylene)glycols (PEG) of various molecular weight (6, 20 and 35 kDa) were incorporated to the structure of fibers to improve compatibility of PLA-drug system and influence the release profiles of hydrophobic drugs. For the systematic development of these materials, it is important to describe the context of the preparation of nanofibers, their morphology and drug release profiles. Therefore, HPLC methods with tandem mass spectrometric or UV detection were optimized and validated to determinate the influence of composition of nanofibers on release kinetics of drugs to different medium (phosphate buffer, hydrogels). The nanofibers with added PEG released significantly higher amounts of drugs and prolonged the release time, compared to the fibers containing only drugs. A multiple...
Methodic of selected judo techniques for younger school age children
Holá, Veronika ; Pavelka, Radim (advisor) ; Vít, Michal (referee)
Title: Methodic of selected judo techniques for younger school age children. Objectives: The aim of the thesis is to build visual material, which has the form of mental maps, selected technic in judo for beginner's athletes during the younger school age. Mental maps will be formed in conjunction with each other in a successful design, failed design, or in individual combinations. Techniques will be selected on the basis of the Testing Regulations of the Czech Judo Association. Methods: The collection of knowledge was carried out by a literature search, which deals with the topic of Juda and the chosen age category. Another reason for choosing the suitability of these techniques is the direct link to the judo test rule, which is given by Czech judo association. Keywords: judo, a younger school age, methods technique, mental maps, combination
The relationship between selected conditional abilities and performance in white water slalom (category C1).
Busta, Jan ; Suchý, Jiří (advisor) ; Lehnert, Michal (referee) ; Bielik, Viktor (referee)
The aim of the study was to identify the relationship between selected fitness skills and the performance demonstrated in nomination races (NR) to the Czech Republic national team (NT) and for the Olympic Games. At the same time, we wanted to determine the optimal level of conditioning assumptions and define a model single-canoe sportsman. We were also searching to determine the differences between Senior NT and Junior NT. The research sample (n=17) of the Czech highest competitions series (Czech Cup) participated in testing to determine level of strength, endurance and partly speed assumptions. There were also measured anthropometric parameters (body dimensions and composition) in detail. Testing took place only 5 weeks before NR. The condition indicators were subsequently correlated with the NR performance. For indicators for which significant and at least moderate correlation were found, the possibility of performance prediction was also found. The highest correlations with performance were found in case of on-water sprints: 20m (rs=0,65), 40m (rs=0,86, resp. rs=0,62), 80m (rs=0,58) and 200m (rs=0,795). The on-water sprints are the only indicators, which could be possibly used for the NR performance prediction. In multiple regression of the 2 40m and 1 200m sprints was found high determination...
Synthesis and evaluation of potential cholinesterases inhibitors
Houngbedji, Neto-Honorius ; Krátký, Martin (advisor) ; Kučerová, Marta (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Organic and Bioorganic Chemistry Author: Neto-Honorius Houngbedji Supervisor: PharmDr. Mgr. Martin Krátký, Ph.D. Title of diploma thesis: Synthesis and evaluation of potential inhibitors of cholinesterases During the last years, the number of patients affected by Alzheimer's disease has been constantly increasing. This disease, which burdens the patients as well as their milieu, requires a costly treatment, based on the use of acetylcholinesterase inhibitors currently. The theoretical part summarizes the contemporary knowledge about the pathology, epidemiology and therapy of Alzheimer's disease. This part also presents the results of previous research of salicylanilide-based cholinesterase inhibitors. The use of acetylcholinesterase inhibitors in the treatment of Alzheimer's disease led to the design of eight novel compounds (esters of salicylanilides and phosphorus acids) with inhibitory activity against cholinesterases. Thus, the experimental part of this diploma thesis consists in the synthesis, characterization and biological evaluation of the novel inhibitors. Finally, three new compounds were synthesized and evaluated successfully. Their inhibitory activities (IC50) were within the range of 48.13-66.13 µM against...
Synthesis and Biological Activity of Novel Natural Product Derivatives
Horký, Pavel ; Pour, Milan (advisor) ; Hampl, František (referee) ; Miletín, Miroslav (referee)
Within the framework of this Thesis, several series of 3,4-diphenylfuranones related to both combretastatin A-4 and antifungal 5-(acyloxymethyl)-3-(halophenyl)-2,5-dihydrofuran-2-ones was prepared. Cytotoxic effects on a panel of cancer and normal cell lines as well as antiinfective activity were evaluated, and the data were complemented with tests for the activation of caspase 3 and 7. High cytotoxicity was observed in some of the halogenated analogues, eg. 3-(3,4-dichlorophenyl)-4-(4-methylphenyl)-2,5-dihydrofuran-2-one with IC50 0.12-0.23 µM, but the compounds were also highly toxic against non-malignant control cells. Interestingly, notable antibacterial activity indicating G(+) selectivity has been found in the 3,4-diarylfuranone class of compounds for the first time. Hydroxymethylation of furanone C5 knocked out cytotoxic effects (up to 40 µM) while maintaining significant activity against Staphylococcus strains in some derivatives. MIC95 of the most promising compound, 3-(4- bromophenyl)-5,5-bis(hydroxymethyl)-4-(4-methylphenyl)-2,5-dihydrofuran-2-one against S. aureus strain ATCC 6538 was 0.98 µM a 3.9 µM after 24 h and 48 h, respectively. Following synthesis of closely related pyrrolidinones, enantioselectivity of the key step (Seyferth-Gilbert homologation) was tested. A new conditions...
Synthesis and evaluation of transdermal drug permeation enhancers
Kopečná, Monika ; Vávrová, Kateřina (advisor) ; Doležal, Pavel (referee) ; Hampl, František (referee)
Penetration enhancers are compounds that facilitate transdermal drug delivery, which is an advantageous pathway of drug administration (compared to conventional methods). However, skin acts as formidable barrier enabling terrestrial life by protecting the inner body from the environmental conditions, microbes and substances. Thus, for drug administration via this pathway, some approach to temporary increase the skin permeability (e.g. permeation enhancer) should be employed. Despite the existence of many enhancer classes, there is still a need for new compounds enhancing broader spectrum of drugs, with reversible mode of action and better safety profile. One of the promising approaches is to explore natural compounds with low toxicity and irritation potential. In this thesis, I first studied various glucose and galactose derivatives bearing structural fragments that were responsible for enhancing activity of previously studied enhancers (e.g. amino acid derivatives, fatty acids and alcohols, modified ceramides). A detailed examination of these sugar- based compounds revealed potent glucoside and galactoside enhancers (12Glc6N and A15) comparable to or better than Span 20 with reversible mode of action and acceptable toxicity on keratinocyte and fibroblast cell lines. Another part of my work builds...
Epigenetic Aspects of normal and malignant hematopoiesis: role of chromatin remodeling ISWIATPase
Zikmund, Tomáš
Chromatin remodeling protein Smarca5 participates on many cellular processes, which are important for tissue development and tumorigenesis. Among these processes utilizing ATPase activity of Smarca5 belong also transcription, replication and DNA repair. We hypothesized that Smarca5 represents essential molecule for chromatin modulation primarily at early developmental stages at the level of fast-dividing progenitors of many origins, in whose the ATPase is highly expressed. To such tissues may belong also hematopoiesis, in which the Smarca5 has highest expression. The subject of my doctoral thesis is therefore analysis of the effect Smarca5 depletion on proliferation and differentiation of hematopoietic progenitors in vivo and a search for mechanisms behind the resulted developmental defects. We utilized conditionally knockout allele of Smarca5 in blood precursors to study in a mouse model how depletion of the ISWI ATPase causes accumulation of earliest progenitors inhibited from further maturation to erythroid and other myeloid lines. The proerythroblasts became dysplastic and the majority of basophilic erythroblasts ceased cycling around the G2/M stage. An expected mechanism for observed changes appeared the activation of stress pathway of protein p53 that is often associated with unrepaired DNA...
Five-members N-heterocycles as potential antituberculotics
Sychra, Pavel ; Hrabálek, Alexandr (advisor) ; Kuneš, Jiří (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Inorganic and Organic Chemistry Candidate: Pavel Sychra Supervisor: prof. PharmDr. Alexandr Hrabálek, CSc. Title of diploma thesis: Five-members N-heterocycles as potential antituberculotics Tuberculosis is widespread infectious disease predominantly caused by Mycobacterium tuberculosis. According to World Health Organization, 10.4 million new cases of tuberculosis and 1.8 million deaths from tuberculosis were registered worldwide only in 2015. In the previous work of our group it was found that 2,5- and 1,5-disubstituted tetrazoles and 2,5-disubstituted oxadiazoles bearing 3,5-dinitrobenzylsulfanyl fragment exhibited outstanding antimycobacterial activities. The aim of this work was to modify these lead structures by removing the methylsulfanyl linker and to prepare a series of 3,5-dinitrophenyl tetrazole and oxadiazole derivatives. Firstly, we prepared a series of 2- and 1-benzyl-5-(3,5-dinitrophenyl)-1H-tetrazoles by the reaction of 5-(3,5-dinitrophenyl)-1H-tetrazole with diversely substituted benzyl halide. In another part, we dealt with the preparation of tetrazole derivatives containing saturated nitrogen heterocycle. At first, it was necessary to prepare alkylating agents, which have been subsequently used for alkylation...
Department of Organic and Bioorganic Chemistry
Brůža, Zbyněk ; Pour, Milan (advisor) ; Tobrman, Tomáš (referee) ; Starý, Ivo (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department Department of Organic and Bioorganic Chemistry Candidate Mgr. Zbyněk Brůža Supervisor prof. RNDr. Milan Pour, Ph.D. Title of Doctoral Thesis Synthesis and application of polysubstituted pyranones This Thesis deals with the development of the isomerization of 5-alkyliden-5,6-dihydro-2H- pyran-2-ones to 6-alkyl-5-methylidene-5,6-dihydro-2H-pyran-2-ones. This process is an unusual version of the intramolecular Tsuji-Trost reaction, the products of which are seemingly thermodynamically unfavourable. The methodology developed through the optimization of the reaction conditions tolerated a broad range of functional groups. Quantum chemistry calculations identified the formation of the pyramidal η2-complex as the key step of the reaction, which made the formation of the final products possible.

Rigorous theses : 15,322 records found   beginprevious7421 - 7430nextend  jump to record:
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