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Synthesis of novel quinazoline derivatives as a potential multipotent therapeutics against Alzheimer's disease
Tošnerová, Daniela ; Karabanovich, Galina (advisor) ; Matouš, Petr (referee)
1 ABSTRACT Charles University, Faculty of Pharmacy in Hradec Králové Department of: Organic and Bioorganic Chemistry Mentor: Ing. Galina Karabanovich, Ph.D. Consultant: Ing. Barbora Svobodová, Ph.D. Student: Daniela Tošnerová Title of Thesis: Synthesis of novel quinazoline derivatives as a potential multipotent therapeutics against Alzheimer's disease Alzheimer's disease (AD) is a severe neurologic disorder. Current treatments only temporarily delay the progression of disease. The main limiting factor for developing of new therapeutic compounds is the simultaneous presence of multiple pathologies. Thus, a new group of potential drugs called multi-target directed ligands (MTDLs) emerged as an alternative option to combat AD. To this date, dozens of MTDLs have been published. As part of the experimetnal section of this thesis, a series of small molecules based on quinazoline scaffold was rationally designed with the intention to influence the activity of acetylcholinesterase, butyrylcholinesterase, monoamine oxidase A and B (MAO-A/MAO-B), and the GluN1/GluN2B subunit of N-methyl-D-aspartate receptor (NMDAR). Subsequently twenty-four new quinazoline derivatives were synthesized, and biologically evaluated. The overall results highlighted compound II-6h ((5E)-8-chlor-N-cyklohexyl-3-methyl-1-...
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Mechanisms responsible for sex bias in the prevalence of autoimmune diseases
Ráček, Vojtěch ; Daňková, Pavlína (advisor) ; Ciferská, Hana (referee)
Studies have shown that women typically have stronger immune responses than men. This can also make them more susceptible to autoimmune diseases, with females comprising 80% of autoimmune patients. In women, one X chromosome is epigenetically silenced through a process called X chromosome inactivation. However, some immune-related genes located on the X chromosome, such as TLR7 and CD40L, may escape this silencing process in certain cells or tissues. This can result in a sex-biased expression that contributes to the development and susceptibility of autoimmune diseases like lupus, rheumatoid arthritis, and Sjögren's syndrome. Another interesting factor that explains this sex bias is lncRNA XIST, which is a primary regulator of the inactivation process. It plays a crucial role in lupus development and creates an XIST ribonucleoprotein complex with proteins that help establish a repressed chromatin state on the inactivated chromosome. Importantly, many of these proteins are autoantigens in various autoimmune diseases and may serve as clinical markers for the diagnosis of these conditions. While microbiome and sexual hormones also play important roles, the focus remains primarily on XIST RNA and escape genes. Keywords: autoimmune disease, sex bias, X chromosome, escape genes, lncRNA XIST, sexual...
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Personality predictors of exercise addiction in competitive sport
Vítková, Tereza ; Mudrák, Jiří (advisor) ; Bezdíček, Ondřej (referee)
Exercise addiction is becoming a recognized concern, particularly prevalent in elite athletic environments where the pursuit of perfection is emphasized. Despite growing awareness of problematic exercise behaviors, research investigating the underlying risk factors remains limited. This study aimed to examine personality predictors of exercise addiction in Czech elite athletes. A sample of 168 competitive athletes, aged 18 to 30 years, completed assessments including the Exercise Addiction Inventory, Sport Motivation Scale-6, the Athletic Identity Measurement Scale, Performance Perfectionism Scale-Sport, and the Neuroticism Scale from Big Five Inventory. In terms of prevalence, the findings revealed that 16.5 % of athletes exhibited problematic signs of exercise addiction, while 76.7 % were potentially at risk with low severity of symptoms. No significant differences were observed between different groups of sports. Using multiple linear regression, the study demonstrated a significant overall effect of personality predictors on exercise addiction. Neuroticism, introjected regulation, and athletic identity were identified as significant predictors of exercise addiction. These findings highlight the importance of psychological factors such as personality traits and motivational regulation in...
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Influence of urbanization patterns on the escape behaviour of birds
Dontová, Alena ; Mikula, Peter (advisor) ; Brlík, Vojtěch (referee)
Urbanization, i.e., the anthropogenic transformation of natural habitats into urban areas, has significant impact on the biodiversity. One of the key factors for successful animal survival in urban environments is the increase in their tolerance towards humans manifested by their decreased shyness. One of the field methods for assessing the level of the shyness across different individuals, populations, and species of animals is measuring their flight initiation distance. In this thesis, I focus primarily on birds, as their responses have been most extensively studied. Previous studies focused on differences in escape behaviour among birds mainly between urban and rural areas, and focused mainly on Europe and North America. However, human settlements vary in their history, size, population density, and other characteristics. Therefore, the observed patterns in bird behaviour may not always be universally applicable across all cities. In this thesis, through a literature review, I summarize how the escape behaviour of birds differs not only between urban and rural environments but also depending on the characteristics of human settlements, such as their size, history, degree of urbanization, the density of the local human population and the ecoregion. I found that the most important characteristics are the...
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Electronic legal transactions with a focus on a simple electronic signature
Švejda, Jiří ; Elischer, David (advisor) ; Zvára, Michael (referee)
Electronic legal transactions with a focus on simple electronic signatures Abstract The thesis is divided into six chapters. The first chapter consists of an introduction. The second chapter presents the general regulation and the meaning of the signature with a brief historical background necessary to assess the possible applicability of earlier conclusions to the current legal regulation. The third chapter is devoted to the current regulation and individual types of electronic signatures, i.e. the division into qualified electronic signature, advanced electronic signature and simple electronic signature and the Czech specificity in the form of advanced electronic signature based on a qualified certificate for electronic signatures, commonly known as recognised electronic signature. The chapter also concludes with a discussion of biometric signature, which is increasingly used in practice. The fourth chapter deals with the written form of legal transactions, i.e. a detailed analysis of the Sections 561 and 562 of the Civil Code, including their interrelation. Furthermore, aspects of digital continuity in higher levels of electronic signatures and their comparison with simple electronic signature are discussed. In the last part of the chapter, different types of electronic contracts and the differences...
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Contract for work in the field of construction
Slámová, Anna ; Macková, Alena (advisor) ; Pohl, Tomáš (referee)
Guardianship in inheritance proceedings Abstract The presented diploma thesis deals with "guardianship in inheritance proceedings". The thesis aims to evaluate the meaning and purpose of the institute of guardianship focused on inheritance proceedings, to describe its legislation and relevant jurisprudence, and answer the question of whether the current legislation on guardianship provides sufficient protection to the rights and interests of persons under special protection participating in court proceedings. The thesis consists of five parts, including an introduction and a conclusion. The first part focuses on inheritance proceedings, its legal regulation, sources, and the proceedings in the context of the legal system. Inheritance proceedings are defined as non-disputed proceedings, and a comparison between non-disputed and disputed proceedings is also given. This part explains the court's jurisdiction, the preconditions, the proceedings' initiation, and the notary's role as a court commissioner. The course of the entire inheritance proceedings and the decisions issued in the proceedings are also described. In the second part, the participation in civil court proceedings is discussed. A general explanation of procedural entities, preconditions for participation such as procedural capacity and capacity to...
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Derivatives of boronic acids as potential drugs I.
Koucká, Kateřina ; Kučerová, Marta (advisor) ; Zitko, Jan (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Student: Kateřina Koucká Supervisor: PharmDr. Marta Kučerová, Ph.D. Consultant: PharmDr. Petr Šlechta Title of diploma thesis: Derivatives of boronic acids as potential drugs I. The thesis includes the design, synthesis, and biological evaluation of boronic acid derivatives. These derivatives were prepared as hybrid compounds containing an amide linker, combining mainly pyrazinoic acids with 4-aminophenylboronic acid. Pyrazinamide is used as 1st line antituberculosis drug and 4-aminophenylboronic acid is a bioisoster of 4-aminobenzoic acid, which is a crucial precursor in the folate pathway. Bioisosteric replacement of the carboxylic group with boronic acid could afford the ability of the compounds to form a reversible covalent bond toward a potential biological target. The presented compounds were synthesized in a two-step reaction. The first step was the condensation of 4-aminophenylboronic acid pinacol ester with different derivatives of (hetero)aryl carboxylic acids, that underwent previous activation. The second step was the deprotection of boronic acid pinacol ester to obtain free boronic acids derivatives. The obtained compounds were screened for their in vitro...
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Molecular mechanisms of heat stress memory in plants
Zelená, Julie ; Hála, Michal (advisor) ; Konrádová, Hana (referee)
Global warming is one of the main factors contributing to the decline in crop yield and overall plant biodiversity. Increasing surface temperatures of the Earth result in heightened demands on plant to cope with heat stress. Heat stress causes various damages to plants, primarily denaturation of cellular proteins, loosening of biomembranes, and accumulation of reactive oxygen species (ROS). Plants cells defend against heat stress through lipid remodeling of membranes, increased production of ROS scavengers, and primarily increased production of heat shock proteins (HSP), which are molecular chaperons maintaining proteins properly folded even at temperatures that would otherwise cause denaturation. Plants have developed mechanism to cope with recurring heat stress, such as heat waves, that is referred to as acquired thermotolerance and is enabled by the plant's ability to undergo stress memory. Key to stress memory is priming, which involves preparing the plant for very strong heat stress by exposing it to milder heat stress beforehand. Following priming, there comes a memory period, that is also called recovery period, during which the cell maintains altered molecular expression and physiology. The mechanisms of heat stress memory are divided into transcriptional and post- transcriptional,...
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André Gide, engaged writer
Poppr, Martin ; Jamek, Václav (advisor) ; Voldřichová - Beránková, Eva (referee)
André Gide, an engaged writer Bc. Martin Poppr The French author André Gide (1869 - 1951) was one of the most important writers of the end of the nineteenth and the first half of the twentieth century and an important figure of the public intellectual life. This thesis analyses to what extent André Gide was a politically and socially engaged author and the reach of his work beyond the world of literature. The method used in this work is a literary critical analysis focused on the author's personality as the key factor for the interpretation of his work. The initial and second part of the thesis summaries the concept of engaged literature developed by Jean-Paul Sartre in his study "Qu'est-ce que la littérature?" and mentions examples of other engaged writers. In this framework, the thesis also deals with the general question of "What is literature?". The third part of the thesis describes the life of André Gide and presents Gide's works which fall under the definition of engaged literature. These include works celebrating human freedom and ethics which attempt to foster the reader's strength and courage, but also Gide's autobiographic works, in which the author himself serves as an honest and liberated role model. This section also covers Gide's participation in the "Dreyfus affair" and in the...
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The influence of roots on the chemical properties of the apoplast and the rhizosphere
Puldová, Kristýna ; Fendrych, Matyáš (advisor) ; Šámalová, Markéta (referee)
Chemical properties of the apoplast and rhizosphere are crucial for plant development and its overall well-being. Apoplast includes space outside the plasma membrane and its content, such as gas, water, and solutes. Changes in apoplast properties significantly influence various processes. One of them is cellular growth - the pH-dependent extension of cell walls. The rhizosphere is the soil environment near and under the influence of roots. It is characterised by abiotic factors like the availability of nutrients and toxic compounds. It is also a space with a high representation of microbiome communities. Plants can significantly influence the chemical properties of both apoplast and rhizosphere to improve their growth conditions. This thesis summarises the most important mechanisms of plants' roots that change these chemical properties, focusing on the model plant Arabidopsis thaliana. It shows how and where these mechanisms intersect and in which way they influence each other. Emphasis is placed on the process of growth regulation and mechanisms of increasing nutrient availability. Keywords: apoplast, rhizosphere, H+ ATPase, root growth, rhizodeposition, root exudates, nutrients, microbiome
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