National Repository of Grey Literature 165 records found  1 - 10nextend  jump to record: Search took 0.00 seconds. 
The effect of alisertib and brigatinib on the activity of selected human carbonyl reducing enzymes.
Lakomá, Petra ; Novotná, Eva (advisor) ; Hofman, Jakub (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Petra Lakomá Supervisor: RNDr. Eva Novotná, Ph.D. Title of diploma thesis: The effect of alisertib and brigatinib on the activity of selected human carbonyl reducing enzymes Key words: brigatinib, alisertib, daunorubicin, inhibition, carbonyl-reducing enzymes Protein kinases are enzymes, whose main function is based on a transfer of phosphate group from ATP to protein substrate. This common posttranslational modification is involved in the regulation of intracellular processes and cell signaling. Altered expression of protein kinases is often coupled with a development of cancer. Inhibition of protein kinases may prevent cancer cell proliferation and induce their cell death. The main aim of the diploma thesis was to measure inhibition potential of protein kinase inhibitors, alisertib and brigatinib, against carbonyl-reducing enzymes. Overexpression of carbonyl-reducing enzymes in cancer cells may cause resistance to drugs followed by failure of chemotherapeutic therapy. In case of antracyclin chemotherapeutic daunorubicin, carbonyl-reducing enzymes reduce the carbonyl in C-13 giving rise a primary metabolite daunorubicinol, which has lower cytotoxic effect but higher cardiotoxicity. The effort to...
Synthesis and evaluation of selected enzyme inhibitors as potential drugs
Vu, Quynh Anh ; Krátký, Martin (advisor) ; Novotná, Eva (referee)
Charles University Faculty of Farmacy in Hradec Králové Department of Organic and Bioorganic Chemistry Author: Bc. Quynh Anh Vu Supervisor: doc. PharmDr. Mgr. Martin Krátký, Ph.D. Title of diploma thesis: Synthesis and evaluation of selected enzyme inhibitors as potential drugs This diploma thesis deals with the synthesis of new inhibitors of the mycobacterial enzyme InhA and inhibitors of acetylcholinesterase and butyrylcholinesterase and their potential inhibitory effect against these three enzymes. All of the prepared compounds are analogues derived from triclosan, which could be convenient candidates as potential drugs for the treatment of tuberculosis and neurodegenerative diseases including Alzheimer's disease. The theoretical part summarizes facts about tuberculosis including the resistance of mycobacteria to antituberculosis drugs and research of new drugs against tuberculosis. Also, the cholinergic hypothesis and the investigation of new potential inhibitors of cholinesterases are described briefly. The experimental part reports the reactions leading to the preparation of designed compounds. The chapter Results and discussion summarizes structure-activity relationships. It also discusses the synthesis and its complications. Eight compounds (two precursors for further syntheses and...
Activity of novel acridine dyes - in vitro study
Pavlová, Dominika ; Macháček, Miloslav (advisor) ; Novotná, Eva (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Dominika Pavlová Supervisor: RNDr. Miloslav Macháček, PhD. Title of diploma thesis: Activity of novel acridine dyes - in vitro study Acridine derivatives are being investigated for their potential in the treatment of many diseases, such as cancer, bacterial infections, and malaria. For example, amsakrin, acting as a topoisomerase poison that interacts with both DNA and human topoisomerase II, is used in clinical practice in conventional antitumor chemotherapy. Derivatives of 9-aminoacridine-4- carboxidoamide act similarly. The master's thesis investigates the in vitro activity of the newly synthesized 9-aminoacridine-4-carboxidoamide derivatives and other derivatives of acridine. The purpose of the thesis was to determine whether the studied compounds FK-8-HCl, FK-20-HCl, FK-27-HCl, FK-36-HCl, FK-42-HCl, FK-46-HCl, FK-48, FK-78-HCl, FK-97- HCl and FK-106 are cytotoxic, what concentration induce inhibition of proliferation, what type of cell death is triggered and whether they inhibit the human topoisomerase II. The human epithelial cell line HeLa was used for cytotoxicity experiments. The neutral red uptake assay was used to determine the cell viability. Cells were exposed to different...
Cartographic cultural heritage
Novotná, Eva ; Papík, Richard (advisor) ; Cajthaml, Jiří (referee) ; Voženílek, Vít (referee)
Disertace je zaměřena na kartografické kulturní dědictví. Zkoumá postupy a stav jeho zpracování i způsoby a nástroje pro zpřístupnění v paměťových institucích. Byly vytčeny dva hlavní cíle práce. Nejprve zpracovat teoretický model online zpřístupnění kartografického kulturního dědictví a ověřit jej na vzorku mapových sbírek. Dále na základě teoretického modelu vytvořit online nástroj pro zlepšení služeb mapových sbírek. K dosažení cíle byly použity kvalitativní výzkumné metody. Konkrétně se jednalo o dotazníkové šetření českých a zahraničních mapových sbírek a také o případové studie českých projektů zaměřených na zpracování a zpřístupnění kartografických památek. K naplnění cílů práce byly podle knihovnického referenčního modelu IFLA navrženy dílčí modely uživatelských úloh, jejichž cílem bylo najít, určit, vybrat, získat a prozkoumat dílo. Na jejich základě byla doporučena kritéria pro hodnocení uživatelských úloh. K ověření funkčnosti modelu došlo testováním 20 digitalizovaných mapových sbírek. Byl vytvořen webový nástroj Databáze digitalizovaných mapových sbírek pro zlepšení služeb mapových sbírek.
Evaluation of Efficiency and Risk of Investment Project
Húsková, Veronika ; Novotná, Eva (referee) ; Hromádka, Vít (advisor)
This bachelor thesis deals with the assessment of the efficiency and risks of an investment project in the field of transport infrastructure. The aim of this work is to evaluate a bicycle lane. The first part of the thesis is the theoretical and describes the stages of evaluation in detail. What follows is a part, which interconnects the theoretical part with a case study. The final part of this work comprises the case study, which includes a description of the evaluated project, economic analysis, and risk assessment. The evaluated project was ii/444 Šternberk-průtah-I.stavba, and for the purpose of the case study only the bicycle trail was assessed. The economic output is based on the outputs of the online system eCBA.
Graduates of the Institute of Translation Studies and their opportunities on the Labour Market
Novotná, Eva ; Čeňková, Ivana (advisor) ; Svoboda, Tomáš (referee)
Filozofická fakulta Univerzity Karlovy nám. Jana Palacha 2, 116 38 Praha 1 IČ: 00216208 DIČ: CZ00216208 Tel.: (+420)221 619 111 http://www.ff.cuni.cz Jedná se o rigorózní práci, která je uznanou diplomovou či disertační prací. Děkujeme za pochopení.
Study on impact of selected protein kinase inhibitors on drug resistance mediated by cytochromes P450
Janoušková, Adéla ; Hofman, Jakub (advisor) ; Novotná, Eva (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Adéla Janoušková Supervisor: RNDr. Jakub Hofman, Ph.D. Title of diploma thesis: Study on impact of selected protein kinase inhibitors on drug resistance mediated by cytochromes P450 Pharmacokinetic drug resistance often leads to failure of an anticancer therapy. One of the mechanisms is increased efflux of drugs from tumour cells, whereas some studies suggest that increased drug conversion to an inactive metabolite might be another contributing mechanism. The aim of this work was to define the possible role of CYP3A4 and CYP2C8 enzymes in the phenomenon of pharmacokinetic resistance and to investigate the possibility of its modulation by new targeted drugs. In the first part, we used the MTT proliferation method together with HepG2 cells stably transduced with particular human enzymes and demonstrated significant involvement of CYP3A4 in docetaxel resistance. In the following part, we examined the inhibitory effects of four selected tyrosine kinase inhibitors on the CYP3A4 activity in intact cells using a commercial kit. Cobimetinib and dabrafenib showed significant inhibitory activity, while osimertinib and brivanib did not. In the final part, we demonstrated the ability of the first two...
Kinetic Evaluation of Potential Inhibitors for Selected Cysteine Proteases
Odvárková, Anna ; Hofman, Jakub (advisor) ; Novotná, Eva (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Anna Odvárková Supervisor: RNDr. Jakub Hofman, Ph.D. Consultants: Carina Lemke Prof. Dr. Michael Gütschow Title of diploma thesis: Kinetic Evaluation of Potential Inhibitors for Selected Cysteine Proteases Cysteine cathepsins are proteases which are naturally present in the human body, taking part in various physiological processes such as cell signaling, proliferation or bone remodeling. However, their dysregulation leads to serious disorders. An aberrant activity of cysteine cathepsins is present in diseases like cancer, osteoporosis, neurodegenerative disorders or autoimmune diseases. Therefore, these enzymes can serve as valuable diagnostic or therapeutic targets. Rhodesain is a parasitic protease produced by Trypanosoma brucei rhodesiense and essential for its survival. This enzyme shares a high homology with human cysteine cathepsin L. Inhibition of rhodesain can be a potential treatment of African trypanosomiasis, also known as sleeping sickness. Inhibitory potency of several compounds against the target enzymes was assayed spectrophotometrically or fluorometrically and the results were evaluated by using linear or non-linear regression. Determination of a Michaelis- Menten constant...
Kinetic Evaluation of Potential Inhibitors for Selected Cysteine Proteases
Odvárková, Anna ; Hofman, Jakub (advisor) ; Novotná, Eva (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Anna Odvárková Supervisor: RNDr. Jakub Hofman, Ph.D. Consultants: Carina Lemke Prof. Dr. Michael Gütschow Title of diploma thesis: Kinetic Evaluation of Potential Inhibitors for Selected Cysteine Proteases Cysteine cathepsins are proteases which are naturally present in the human body, taking part in various physiological processes such as cell signaling, proliferation or bone remodeling. However, their dysregulation leads to serious disorders. An aberrant activity of cysteine cathepsins is present in diseases like cancer, osteoporosis, neurodegenerative disorders or autoimmune diseases. Therefore, these enzymes can serve as valuable diagnostic or therapeutic targets. Rhodesain is a parasitic protease produced by Trypanosoma brucei rhodesiense and essential for its survival. This enzyme shares a high homology with human cysteine cathepsin L. Inhibition of rhodesain can be a potential treatment of African trypanosomiasis, also known as sleeping sickness. Inhibitory potency of several compounds against the target enzymes was assayed spectrophotometrically or fluorometrically and the results were evaluated by using linear or non-linear regression. Determination of a Michaelis- Menten constant...
The detection of protein covalent complexes with DNA using fluorescent microscopy
Melicharová, Růžena ; Jirkovská, Anna (advisor) ; Novotná, Eva (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department od Biochemical Sciences Candidate: Růžena Melicharová Supervisor: PharmDr. Anna Jirkovská, Ph.D. Title of thesis: The detection of protein covalent complexes with DNA using fluorescent microscopy Anthracycline antibiotics are present one of the most potent antineoplastic drugs. The mechanism of their action is complex. They are reported to intercalate to DNA, form DNA adducts and interact with topoisomerase II (TopII) as its poisons. Catalytic cycle of TopII is interrupted when anthracyclines stabilize the covalent complex of DNA and TopII and that causes cell damage. However, using of anthracyclines is limited by several adverse effects e. g. myelotoxicity and cardiotoxicity. The mechanism of cardiotoxicity is still unclear but may be associated with poisoning of the TopIIβ isoform. Unlike the TopIIα, TopIIβ is present mostly in quiescent cells as cardiomyocytes. Furthermore, the only clinically approved cardioprotective drug dexrazoxane belongs to TopII catalytic inhibitors. Nevertheless, the details of the dexrazoxane-afforded protection are unclear. This thesis was aimed to optimize the TARDIS (trapped in agarose DNA immunostaining) assay to detect and quantify covalent cleavage complexes, compare different ways for analysis of...

National Repository of Grey Literature : 165 records found   1 - 10nextend  jump to record:
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