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Mycobacterium tuberculosis - structure and functions of the cell wall
Kukrálová, Simona ; Janďourek, Ondřej (advisor) ; Jílek, Petr (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Study program: Bioanalytical laboratory diagnostics in healthcare Candidate: Bc. Simona Kukrálová Supervisor: PharmDr. Ondřej Janďourek, Ph.D. Title of diploma thesis: Mycobacterium tuberculosis - structure and functions of the cell wall Mycobacterium tuberculosis is an intracellular pathogen that causes a disease called tuberculosis, which, along with other selected diseases, is still one of the leading causes of mortality in the world. It is estimated that more than a million people succumb to the disease each year. The remarkable structure of the cell wall of mycobacteria has a great influence on the treatment of tuberculosis itself, together with the ever-increasing incidence of multidrug- resistant and extensively resistant strains, especially in Mycobacterium tuberculosis. The research of mycobacteria is given great attention. Efforts to find new substances with antimycobacterial effect acting on individual components of the cell wall, preferably on the cell wall as a complex, are actual and are part of national as well as international programs. Theoretical part of this diploma thesis deals with current knowledge about mycobacteria with emphasis on cell wall, epidemiology of tuberculosis...
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Synthesis and evaluation of potential antimycobacterial agents based on hydrazine derivatives
Koklarová, Apolena ; Krátký, Martin (advisor) ; Vinšová, Jarmila (referee)
Based on research in past years, we have synthetized two similar series of compounds with potential antimycobacterial activity. First series based on isoniazid are (E)-4-[(2- isonicotinoylhydrazineylidene)methyl]-N-phenylbenzamides with great activity (MIC for Mtb. of 0.03-0.125 μM) with few derivatives with moderate activity on nontuberculous mycobacterium M. kansasii (MIC of 2-4 μM). In second series pyridin-4-yl moiety has been exchanged for 3,5-dinitrophenyl, which has shown to be highly effective antimycobacterial scaffold in recent years, therefore derivatives of (E)-4-{[2-(3,5- dinitrobenzoyl)hydrazineylidene]methyl}-N-phenylbenzamide have been prepared. These molecules have shown moderate activity against drug-susceptible Mtb. (MIC of 2-32 μM), and only 4-chloro derivative has surprisingly high activity against non-tuberculous M. avium (MIC of 16-32 μM). Four molecules from the second series even exhibit some activity against MDR- TB and XDR-TB strains.
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Introduction of an invertebrate animal model, Galleria Galleria mellonellamellonella, to study the in vivo efficacy of existing and newly synthesized, candidate antituberculotics
Kubíček, Jiří ; Konečná, Klára (advisor) ; Němečková, Ivana (referee)
Charles university, Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Study program: Pharmacy Author: Jiří Kubíček Supervisor: RNDr. Klára Konečná, Ph.D. Title of thesis: Introduction of an invertebrate animal model, Galleria mellonella, to study the in vivo efficacy of existing and newly synthesized, candidate antituberculotics. Background: The aim of this diploma thesis has been to present an invertebrate organism, Galleria mellonella (G. mellonella), Pyralidae, as an alternative, more economically advantegous and morally more acceptable model for in vivo studies of an antituberculotics (anti-TB) efficacy. In the experimental part of this work, attention was paid to the optimization of methodological steps, that should lead to a higher reproducibility and validity of the obtained data. The effect of the disaggregating supplement, tyloxapol, on the growth of Mycobacterium aurum (M. aurum) was evaluated. The growth of this microbial strain in the culture medium, Middlebrook 7H9, was also mapped to determine the exponential growth phase. In the second part of the experiments, G. mellonella larvae were infected with a M. aurum bacterial strain, followed by an administration of the selected, commercially available anti-TB. Methods: To map the exponential phase of M....
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In vitro screening of potential antimycobacterial compounds against fast growing strains of Mycobacterium genus
Židková, Lenka ; Janďourek, Ondřej (advisor) ; Jílek, Petr (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Study program: Specialist in Laboratory Methods Candidate: Bc. Lenka Lyčková Supervisor: PharmDr. Ondřej Janďourek, Ph.D. Title of diploma thesis: In vitro screening of potential antimycobacterial compounds against fast growing strains of Mycobacterium genus The aim of this work is to determine the efficacy of new compounds for possible treatment of tuberculosis in the future. A microdilution broth method with already proven procedure on Mycobacterium aurum and Mycobacterium smegmatis strains was used to determine the minimum inhibitory concentration of compounds. The theoretical part summarizes the epidemiological situation of recent years with global trends in the incidence and mortality of tuberculosis in the world and in the Czech Republic, including prospective plans for remediation in the time horizon. Mycobacteria are described in the main representation with M. tuberculosis. Tuberculosis disease - its history, forms, diagnosis and treatment with antituberculotics, which are divided according to the use lines, new drugs and drugs in development. The experimental part contains qualitative and quantitative methods of testing mycobacteria and captures the microdilution broth method used in...
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Synthesis and evaluation of potential antimycobacterial agents based on hydrazine derivatives
Koklarová, Apolena ; Krátký, Martin (advisor) ; Vinšová, Jarmila (referee)
Based on research in past years, we have synthetized two similar series of compounds with potential antimycobacterial activity. First series based on isoniazid are (E)-4-[(2- isonicotinoylhydrazineylidene)methyl]-N-phenylbenzamides with great activity (MIC for Mtb. of 0.03-0.125 μM) with few derivatives with moderate activity on nontuberculous mycobacterium M. kansasii (MIC of 2-4 μM). In second series pyridin-4-yl moiety has been exchanged for 3,5-dinitrophenyl, which has shown to be highly effective antimycobacterial scaffold in recent years, therefore derivatives of (E)-4-{[2-(3,5- dinitrobenzoyl)hydrazineylidene]methyl}-N-phenylbenzamide have been prepared. These molecules have shown moderate activity against drug-susceptible Mtb. (MIC of 2-32 μM), and only 4-chloro derivative has surprisingly high activity against non-tuberculous M. avium (MIC of 16-32 μM). Four molecules from the second series even exhibit some activity against MDR- TB and XDR-TB strains.
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Pathogenesis of infectious disease caused by bacterium Mycobacterium tuberculosis
Doležalová, Klára ; Janďourek, Ondřej (advisor) ; Kovařík, Miroslav (referee)
Charles University Faculty of Pharmacy in Hradec Kralove Department of Biological and Medical Sciences Study programme: Bioanalytical laboratory diagnostics in health care Author: Bc. Klára Doležalová Supervisor of diploma thesis: PharmDr. Ondřej Janďourek, Ph.D. Title of diploma thesis: Pathogenesis of infectious disease caused by bacterium Mycobacterium tuberculosis The theoretical part of this diploma thesis is concerned about tuberculosis where the main part of the thesis is focused on pathogenesis of this disease. Tuberculosis is recognized as highly infectious disease leading to the total exhaustion of the organism. The main causative agent of the above mentioned disease is Mycobacterium tuberculosis, which is transmitted to respiratory tract via inhalation of droplets from infected person and leads to the granuloma formation. For tuberculosis is typical a creation of granulomas, mainly with caseous necrosis. Highly important is accurate diagnosis and appropriately chosen treatment. The treatment consists of a long-term administration of antituberculotic drugs in combinations. The development of the resistance to one or more antituberculotics is adverse complication within the treatment procedure. The experimental part of this work pays attention to the testing of antimycobacterial activity...
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Mycobacterium tuberculosis - structure and functions of the cell wall
Kukrálová, Simona ; Janďourek, Ondřej (advisor) ; Jílek, Petr (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Study program: Bioanalytical laboratory diagnostics in healthcare Candidate: Bc. Simona Kukrálová Supervisor: PharmDr. Ondřej Janďourek, Ph.D. Title of diploma thesis: Mycobacterium tuberculosis - structure and functions of the cell wall Mycobacterium tuberculosis is an intracellular pathogen that causes a disease called tuberculosis, which, along with other selected diseases, is still one of the leading causes of mortality in the world. It is estimated that more than a million people succumb to the disease each year. The remarkable structure of the cell wall of mycobacteria has a great influence on the treatment of tuberculosis itself, together with the ever-increasing incidence of multidrug- resistant and extensively resistant strains, especially in Mycobacterium tuberculosis. The research of mycobacteria is given great attention. Efforts to find new substances with antimycobacterial effect acting on individual components of the cell wall, preferably on the cell wall as a complex, are actual and are part of national as well as international programs. Theoretical part of this diploma thesis deals with current knowledge about mycobacteria with emphasis on cell wall, epidemiology of tuberculosis...
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Introduction of an invertebrate animal model, Galleria Galleria mellonellamellonella, to study the in vivo efficacy of existing and newly synthesized, candidate antituberculotics
Kubíček, Jiří ; Konečná, Klára (advisor) ; Němečková, Ivana (referee)
Charles university, Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Study program: Pharmacy Author: Jiří Kubíček Supervisor: RNDr. Klára Konečná, Ph.D. Title of thesis: Introduction of an invertebrate animal model, Galleria mellonella, to study the in vivo efficacy of existing and newly synthesized, candidate antituberculotics. Background: The aim of this diploma thesis has been to present an invertebrate organism, Galleria mellonella (G. mellonella), Pyralidae, as an alternative, more economically advantegous and morally more acceptable model for in vivo studies of an antituberculotics (anti-TB) efficacy. In the experimental part of this work, attention was paid to the optimization of methodological steps, that should lead to a higher reproducibility and validity of the obtained data. The effect of the disaggregating supplement, tyloxapol, on the growth of Mycobacterium aurum (M. aurum) was evaluated. The growth of this microbial strain in the culture medium, Middlebrook 7H9, was also mapped to determine the exponential growth phase. In the second part of the experiments, G. mellonella larvae were infected with a M. aurum bacterial strain, followed by an administration of the selected, commercially available anti-TB. Methods: To map the exponential phase of M....
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Mycobacterium tuberculosis as causative agent of grave illness
Hampl, Tomáš ; Janďourek, Ondřej (advisor) ; Voxová, Barbora (referee)
Charles University, Faculty of Pharmacy, Hradec Králové Field of study: Specialist in laboratory methods Author: Bc. Tomáš Hampl Supervisor: PharmDr. Ondřej Janďourek, Ph.D. Title of diploma thesis: Mycobacterium tuberculosis as causative agent of grave illness The aim of this diploma thesis is to deal with tuberculosis, describe the pathogen, taxonomic classification, describe the origin, course and clinical manifestations of the disease, diagnosis, including laboratory diagnostics, epidemiology of tuberculosis, treatment and prevention. Tuberculosis (TBC) is one of the deadliest infectious diseases in the world caused by bacterium M. tuberculosis in humans. TBC is sometimes referred as a disease of the past, but the recent rise in cases of the disease, and especially the spread of forms of drug-resistant TBC, makes the disease very dangerous. Currently, a major problem is the alarming rise in resistant and multi-resistant tuberculosis, which is not counteracted by commonly used first-line drugs. Therefore, there is a constant emphasis around the world on discovering and testing new potential antituberculotics that could help patients with resistant and multidrug-resistant TBC. In the experimental part, the thesis deals with screening of antimycobacterial activity of potential antituberculotics...
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In vitro screening of potential antimycobacterial compounds against fast growing strains of Mycobacterium genus II
Pchálková, Tereza ; Janďourek, Ondřej (advisor) ; Jílek, Petr (referee)
Charles University Faculty of Pharmacy in Hradec Kralove Department of Biological and Medical Sciences Study program: Specialist on Laboratory Methods Author: Bc. Tereza Pchálková Supervisor: PharmDr. Ondřej Janďourek, Ph.D. Title of diploma thesis: In vitro screening of potential antimycobacterial compounds active against fast growing strains of Mycobacterium genus II Key words: Mycobacteria, Tuberculosis, Antituberculotics, Microdilution broth method, Minimum inhibition concentration Background: The aim of this diploma thesis has been screening of in vitro antimycobacterial activity of novel compounds against fast growing strains of the genus Mycobacterium (Mycobacterium smegmatis and Mycobacterium aurum). Another aim has been predicting the structure-activity relationships for tested compounds. Methods: The technique used for activity determination was microdilution broth method. The value of minimum inhibition concentration for each compound was determined. The evaluation was performed visually and spectrophotometrically using the Alamar blue indicator. Results: A total of 79 compounds were tested. 22 tested compounds showed significant activity against mycobacteria. The substances were sorted according to the similarity in chemical structure into 10 groups. From a chemical point of view, these...
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