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Study of pyridine derivatives as potential antimycobacterial active drugs.
Nawrot, Daria Elżbieta ; Doležal, Martin (advisor) ; Musílek, Kamil (referee) ; Musiol, Robert (referee)
Univerzita Karlova, Farmaceutická fakulta v Hradci Králové Katedra Katedra farmaceutické chemie a farmaceutické analýzy Kandidát: Daria Nawrot Školitel: Prof. PharmDr. Martin Doležal, Ph.D. Název disertační práce: Studium derivátů pyridinu jako potenciálních antimykobakteriálních léčiv. Mimo období kdy tvořil COVID-19 největší hrozbu pro účinnost zdravotnických systémů na celosvětovém měřítku, zůstává tuberkuloza nejdůležitější příčinou úmrtí na infekční chorobu. Tato skutečnost, spolu se stoupající antibakteriální rezistencí, tvoří zásadní výzvu pro výzkum nových léčiv. Teoretická část tohoto komentáře krátce zvýrazňuje problematiku tuberkulozy a konkrétněji antimikrobiální rezistence. V experimentální části je vedena diskuze o návrhu, syntéze a biologickém hodnocení nových sloučenin zkoumaných během doktorského studia. Navržené sloučeniny byly připraveny a testovány na in vitro aktivitu proti vybraným mykobakteriálním kmenům (M. Avium, M. aurum, M. kansasii, M. smegmatis spolu s kmeny hlavního zájmu - Mtb H37Ra a H37Rv), osmi fungálním kmenům (Candida albicans, Candida krusei, Candida parapsilosis, Candida tropicalis, Aspergillus fumigatus, Aspergillus flavus, Absidia corymbifera, a Trichophyton interdigitale) a osmi bakteriálním kmenům (Staphylococcus aureus, Escherichia coli, Pseudomonas...
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Derivatives of pyrazinecarboxylic acid as potential antimycobacterial active drugs.
Bouz, Ghada Basem ; Doležal, Martin (advisor) ; Musiol, Robert (referee) ; Krátký, Martin (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Candidate Ghada Bouz Supervisor Prof. PharmDr. Martin Doležal, Ph.D. Title of Doctoral Thesis Derivatives of Pyrazinecarboxylic Acid as Potential Antimycobacterial Active Drugs This doctoral thesis is focused on the design, synthesis, and in vitro antimicrobial evaluation of potentially active compounds structurally derived from the first line antitubercular, pyrazinamide. The introduction briefly highlights the serious issue of tuberculosis in the present time, along with the reasons behind the failure to eradicate this ancient infection. The lack of a proper animal model that can replicate tuberculosis in its latent and active form was discussed more in detail, where zebrafish (Danio rerio) was suggested as a novel animal model suitable for multi-research purposes connected to tuberculosis. A total of 112 compounds were synthesized and published as part of this doctoral work. They are divided into four main structural types, namely 3-(phenylcarbamoyl)pyrazine-2-carboxylic acids, 3- aminopyrazine-2-carboxamides, ureidopyrazines, and N-(pyrazin-2-yl)benzenesulfonamides. All prepared compounds were in vitro screened against five mycobacterial strains (with the...
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Screening of novel chelators of microbiogenic metals
Catapano, Maria Carmen ; Mladěnka, Přemysl (advisor) ; Hrdina, Radomír (referee) ; Musiol, Robert (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Maria Carmen Catapano, MSc. Supervisor: Assoc. Prof. Přemysl Mladěnka, PharmD., Ph.D. Co-supervisor: Assoc. Prof. Laura Mercolini, Ph.D. Title of Doctoral Thesis: Screening of novel chelators of microbiogenic metals Iron, copper and zinc are microbiogenic elements which play crucial roles in a series of physiological processes in human organism. Homeostasis of these transition metals is strictly regulated since, among others: a) free or loosely bound iron or copper can catalyse the production of hydroxyl radical; b) lack of zinc but also of the previously mentioned metals is associated with significant impairments. Hereditary hemochromatosis, transfusion-induced secondary iron overload and Wilson's disease are known as pathological conditions associated with metal overload in the organism. Chelator agents have vital relevance for the treatment of these impairments. There are also numerous diseases with homeostatic imbalances in iron, copper and or zinc: neurodegenerative diseases, cardiovascular diseases, cancer and diabetes mellitus. Different chelating compounds have been examined for the treatment of these impairments. The aim of this doctoral thesis was to perform a screening of metal...
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