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Preparation of Pyrazinamide Derivatives as Potential Antiinfectives. (Study of Structure Activity Relationships)
Juhás, Martin ; Zitko, Jan (advisor) ; Vávrová, Kateřina (referee) ; Svobodová, Radka (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Training Workplace Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Doctoral Degree Program Pharmaceutical Chemistry Candidate PharmDr. Martin Juhás Supervisor doc. PharmDr. Jan Zitko, Ph.D. Advisor prof. PharmDr. Martin Doležal, Ph.D. Title of Doctoral Thesis Preparation of Pyrazinamide Derivatives as Potential Antiinfectives. (Study of Structure Activity Relationships) Antimicrobial resistance is considered one of the greatest threats of the 21st century. Until the COVID-19 pandemic, tuberculosis (TB) was the deadliest infectious disease, responsible for approx. one and a half million deaths each year. Resistance is very common in TB. Therefore, this work deals with the research of new potential antimicrobial substances with a particular focus on the activity against Mycobacterium tuberculosis, the main cause of TB. The introduction of this work briefly describes the current state of research on derivatives of pyrazinamide, which served as the prototype structure of the prepared substances and follows with a basic overview of modern computer-based methods used in drug design. The next part comments on the used chemical and biological methods, and the obtained structure-activity relationships in the presented publications....
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Definition of the carbohydrate binding capacities of the novel enterotoxin LT-IIc
Juhás, Martin ; Doležal, Martin (advisor) ; Jirkovská, Anna (referee)
Diarrhoea as a disease is still the leading cause of malnutrition and a major cause of deaths in children under 5 years of age in the low-income countries. Additionally, it is the most common health problem associated with travelling to the developing countries. In all the mentioned cases, enterotoxigenic E. coli (ETEC) is one of the most frequent causes. ETEC is defined as a pathogenic strain of E. coli producing enterotoxins. So far, two types of enterotoxins have been identified: heat-stable (ST) and heat-labile (LT). LTs are further divided into two categories based on their relatedness with cholera toxin to type I (LT-I) and type II (LT-II). All of these enterotoxins have been found to bind to carbohydrate structures on glycosphingolipids by their respective B subunits, however, their binding patterns differ. While LT-I, LT-IIa and LT-IIb have been previously studied in terms of binding specificities, the newest LT-IIc was tested only on few commercially available ganglio-series gangliosides. In this thesis, the binding capabilities of this novel enterotoxin were re-examined by series of binding assays using more ganglio-series and some neolacto-series gangliosides as well as other glycolipids and glycoproteins, to establish the basics of the recognition pattern and to characterize the optimal...
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Definition of the carbohydrate binding capacities of the novel enterotoxin LT-IIc
Juhás, Martin ; Doležal, Martin (advisor) ; Jirkovská, Anna (referee)
Diarrhoea as a disease is still the leading cause of malnutrition and a major cause of deaths in children under 5 years of age in the low-income countries. Additionally, it is the most common health problem associated with travelling to the developing countries. In all the mentioned cases, enterotoxigenic E. coli (ETEC) is one of the most frequent causes. ETEC is defined as a pathogenic strain of E. coli producing enterotoxins. So far, two types of enterotoxins have been identified: heat-stable (ST) and heat-labile (LT). LTs are further divided into two categories based on their relatedness with cholera toxin to type I (LT-I) and type II (LT-II). All of these enterotoxins have been found to bind to carbohydrate structures on glycosphingolipids by their respective B subunits, however, their binding patterns differ. While LT-I, LT-IIa and LT-IIb have been previously studied in terms of binding specificities, the newest LT-IIc was tested only on few commercially available ganglio-series gangliosides. In this thesis, the binding capabilities of this novel enterotoxin were re-examined by series of binding assays using more ganglio-series and some neolacto-series gangliosides as well as other glycolipids and glycoproteins, to establish the basics of the recognition pattern and to characterize the optimal...
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Definition of the carbohydrate binding capacities of the novel enterotoxin LT-IIc
Juhás, Martin ; Doležal, Martin (advisor) ; Jirkovská, Anna (referee)
Diarrhoea as a disease is still the leading cause of malnutrition and a major cause of deaths in children under 5 years of age in the low-income countries. Additionally, it is the most common health problem associated with travelling to the developing countries. In all the mentioned cases, enterotoxigenic E. coli (ETEC) is one of the most frequent causes. ETEC is defined as a pathogenic strain of E. coli producing enterotoxins. So far, two types of enterotoxins have been identified: heat-stable (ST) and heat-labile (LT). LTs are further divided into two categories based on their relatedness with cholera toxin to type I (LT-I) and type II (LT-II). All of these enterotoxins have been found to bind to carbohydrate structures on glycosphingolipids by their respective B subunits, however, their binding patterns differ. While LT-I, LT-IIa and LT-IIb have been previously studied in terms of binding specificities, the newest LT-IIc was tested only on few commercially available ganglio-series gangliosides. In this thesis, the binding capabilities of this novel enterotoxin were re-examined by series of binding assays using more ganglio-series and some neolacto-series gangliosides as well as other glycolipids and glycoproteins, to establish the basics of the recognition pattern and to characterize the optimal...
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Definition of the carbohydrate binding capacities of the novel enterotoxin LT-IIc
Juhás, Martin ; Doležal, Martin (advisor) ; Jirkovská, Anna (referee)
Diarrhoea as a disease is still the leading cause of malnutrition and a major cause of deaths in children under 5 years of age in the low-income countries. Additionally, it is the most common health problem associated with travelling to the developing countries. In all the mentioned cases, enterotoxigenic E. coli (ETEC) is one of the most frequent causes. ETEC is defined as a pathogenic strain of E. coli producing enterotoxins. So far, two types of enterotoxins have been identified: heat-stable (ST) and heat-labile (LT). LTs are further divided into two categories based on their relatedness with cholera toxin to type I (LT-I) and type II (LT-II). All of these enterotoxins have been found to bind to carbohydrate structures on glycosphingolipids by their respective B subunits, however, their binding patterns differ. While LT-I, LT-IIa and LT-IIb have been previously studied in terms of binding specificities, the newest LT-IIc was tested only on few commercially available ganglio-series gangliosides. In this thesis, the binding capabilities of this novel enterotoxin were re-examined by series of binding assays using more ganglio-series and some neolacto-series gangliosides as well as other glycolipids and glycoproteins, to establish the basics of the recognition pattern and to characterize the optimal...
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