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Development of electrochemical methods for study of antibacterial compounds in small volumes
Gajdár, Július ; Barek, Jiří (advisor) ; Šiškanova, Tatiana (referee) ; Labuda, Ján (referee)
Main goal of this Ph.D. thesis is to develop voltammetric methods for the electrochemical study of novel antimycobacterial compounds hydroxynaphthalene- carboxamides. Firstly, this study was focused on the miniaturization of voltammetric methods and construction of an electrochemical microcell due to usually small volume of samples that are associated with an analysis of biologically active compounds in biological matrices. Therefore, all aspects of the voltammetric procedure were studied in a relation to miniaturization. Microcells were based on commercially available electrodes: glassy carbon electrode as a reliable electrode material with well-described characteristics and a novel silver solid amalgam electrode. This study was carried out with analytes 4-nitrophenol, pesticide difenzoquat, and 1-hydroxy-N-(4-nitrophenyl)naphthalene-2-carboxamide. Attention was paid especially to the optimization of oxygen removal procedures in the drop of a solution. Developed miniaturized methods had the same parameters for the determination of studied compounds as in bigger volumes. The proposed electrochemical microcell can be generally used for voltammetric analysis of those samples of biological or environmental origin that are usually available in very limited volumes. Second part of the thesis was focused...
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Synthesis and evaluation of antimycobacterial 1,3,4-oxadiazole derivatives
Šikorová, Enikő ; Krátký, Martin (advisor) ; Vinšová, Jarmila (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Organic and Bioorganic Chemistry Author: Enikő Šikorová Supervisor: doc. PharmDr. Mgr. Martin Krátký, Ph.D. Consultant: Mgr. Václav Pflégr Title of diploma thesis: Synthesis and evaluation of antimycobacterial 1,3,4-oxadiazole derivatives Tuberculosis (TB) is a serious infectious disease caused by obligately pathogenic rods of Mycobacterium tuberculosis complex (Mtb.), and it is still among the ten most common causes of death worldwide. One of the main complications of TB therapy is the ever-increasing resistance of mycobacterial strains to conventional drugs. Therefore, the development of new antimycobacterial compounds is crucial to overcome this issue. Research and development of new potential antimycobacterial agents often involve structure modifications of clinically used drugs - frequently the first-line drug, isoniazid (INH). The starting point of this work is also the structure of the already mentioned INH. First, a series of 2-alkyl-5-(pyridine-4-yl)-1,3,4-oxadiazoles and N'-acylisonicotinohydrazides as their synthetic precursors were prepared and evaluated with very promising activity (expressed as minimal inhibitory concentration - MIC) against several mycobacterial strains (MIC Mtb. H37Rv of 1-8 µM). Furthermore,...
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Modification of antimycobacterial active sulphonamides
Kufa, Martin ; Krátký, Martin (advisor) ; Vinšová, Jarmila (referee)
The importance of the searching for novel antimycobacterial active agents is continually increasing with growing mycobacterial resistance to currently used drugs. However, the resistance-related problems are also associated with other bacteria and fungi. The systematic modification of compounds with a known antimicrobial activity represents one of the possible approaches to overcome this problem. Sulphonamide derivatives may be considered to be such a kind of compounds. That is why we synthesized various sulphathiazole derivatives. Amides were obtained by the reaction of sulphathiazole with appropriate acyl chlorides, substituted ureas from corresponding isocyanates. These ureas were cyclized via oxalyl chloride to form substituted 2,4,5-trioxoimidazolidines. Among derivatives evaluated for their antimycobacterial action, 4-(3- phenethylureido)-N-(thiazol-2-yl)benzenesulphonamide showed the highest activity. Its minimum inhibitory concentrations (MIC) against Mycobacterium tuberculosis My 331/88 (4 µmol/l) were superior to those obtained for sulphathiazole. In the case of nontuberculous mycobacteria (M. avium My 330/88, M. kansasii My 235/88 and M. kansasii My 6509/96), their activities were comparable (≥ 2 µmol/l). Amides showed also a significant antimycobacterial activity, especially against M....
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Development of electrochemical methods for study of antibacterial compounds in small volumes
Gajdár, Július
Main goal of this Ph.D. thesis is to develop voltammetric methods for the electrochemical study of novel antimycobacterial compounds hydroxynaphthalene- carboxamides. Firstly, this study was focused on the miniaturization of voltammetric methods and construction of an electrochemical microcell due to usually small volume of samples that are associated with an analysis of biologically active compounds in biological matrices. Therefore, all aspects of the voltammetric procedure were studied in a relation to miniaturization. Microcells were based on commercially available electrodes: glassy carbon electrode as a reliable electrode material with well-described characteristics and a novel silver solid amalgam electrode. This study was carried out with analytes 4-nitrophenol, pesticide difenzoquat, and 1-hydroxy-N-(4-nitrophenyl)naphthalene-2-carboxamide. Attention was paid especially to the optimization of oxygen removal procedures in the drop of a solution. Developed miniaturized methods had the same parameters for the determination of studied compounds as in bigger volumes. The proposed electrochemical microcell can be generally used for voltammetric analysis of those samples of biological or environmental origin that are usually available in very limited volumes. Second part of the thesis was focused...
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Development of electrochemical methods for study of antibacterial compounds in small volumes
Gajdár, Július
Main goal of this Ph.D. thesis is to develop voltammetric methods for the electrochemical study of novel antimycobacterial compounds hydroxynaphthalene- carboxamides. Firstly, this study was focused on the miniaturization of voltammetric methods and construction of an electrochemical microcell due to usually small volume of samples that are associated with an analysis of biologically active compounds in biological matrices. Therefore, all aspects of the voltammetric procedure were studied in a relation to miniaturization. Microcells were based on commercially available electrodes: glassy carbon electrode as a reliable electrode material with well-described characteristics and a novel silver solid amalgam electrode. This study was carried out with analytes 4-nitrophenol, pesticide difenzoquat, and 1-hydroxy-N-(4-nitrophenyl)naphthalene-2-carboxamide. Attention was paid especially to the optimization of oxygen removal procedures in the drop of a solution. Developed miniaturized methods had the same parameters for the determination of studied compounds as in bigger volumes. The proposed electrochemical microcell can be generally used for voltammetric analysis of those samples of biological or environmental origin that are usually available in very limited volumes. Second part of the thesis was focused...
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Development of electrochemical methods for study of antibacterial compounds in small volumes
Gajdár, Július ; Barek, Jiří (advisor) ; Šiškanova, Tatiana (referee) ; Labuda, Ján (referee)
Main goal of this Ph.D. thesis is to develop voltammetric methods for the electrochemical study of novel antimycobacterial compounds hydroxynaphthalene- carboxamides. Firstly, this study was focused on the miniaturization of voltammetric methods and construction of an electrochemical microcell due to usually small volume of samples that are associated with an analysis of biologically active compounds in biological matrices. Therefore, all aspects of the voltammetric procedure were studied in a relation to miniaturization. Microcells were based on commercially available electrodes: glassy carbon electrode as a reliable electrode material with well-described characteristics and a novel silver solid amalgam electrode. This study was carried out with analytes 4-nitrophenol, pesticide difenzoquat, and 1-hydroxy-N-(4-nitrophenyl)naphthalene-2-carboxamide. Attention was paid especially to the optimization of oxygen removal procedures in the drop of a solution. Developed miniaturized methods had the same parameters for the determination of studied compounds as in bigger volumes. The proposed electrochemical microcell can be generally used for voltammetric analysis of those samples of biological or environmental origin that are usually available in very limited volumes. Second part of the thesis was focused...
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Synthesis and antiinfective evaluation of substituted N-(pyrazin-2-yl)benzenesulfonamides
Paredes De La Red, Cristina ; Doležal, Martin (advisor) ; Kučerová, Marta (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Author: Cristina Paredes de la Red Supervisor: prof. PharmDr. Martin Doležal, Ph.D. Title of diploma thesis: Synthesis and antiinfective evaluation of substituted N-(pyrazine-2- yl)benzenesulfonamide Tuberculosis (TB) is among the ten leading causes of death, especially in developing countries. Even though it is an old disease with established treatment regimen, there has been an increased resistance to anti-TB drugs 1 . The anti-tubercular pyrazinamide has caught the attention of researchers as the different theories for its mechanism of action have made it an interesting entity for further investigation. Here we will discuss N-(pyrazine-2-yl)benzenesulfonamides (General structure is presented in the Figure below) as a new derivatization approach based on synergism methodology between pyrazinamide and sulfonamides. Sulfonamides exert their antimicrobial effect by competitive inhibition of folic acid synthesis and subsequent inhibition of bacterial growth and reproduction 18 . I have contributed to the synthesis and purification of 8 compounds in a series of total 22 N- pyrazinylsulfonamides. Two of the prepared compounds showed activity against Mycobacterium kansasii [2a (MIC...
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Modification of antimycobacterial active sulphonamides
Kufa, Martin ; Krátký, Martin (advisor) ; Vinšová, Jarmila (referee)
The importance of the searching for novel antimycobacterial active agents is continually increasing with growing mycobacterial resistance to currently used drugs. However, the resistance-related problems are also associated with other bacteria and fungi. The systematic modification of compounds with a known antimicrobial activity represents one of the possible approaches to overcome this problem. Sulphonamide derivatives may be considered to be such a kind of compounds. That is why we synthesized various sulphathiazole derivatives. Amides were obtained by the reaction of sulphathiazole with appropriate acyl chlorides, substituted ureas from corresponding isocyanates. These ureas were cyclized via oxalyl chloride to form substituted 2,4,5-trioxoimidazolidines. Among derivatives evaluated for their antimycobacterial action, 4-(3- phenethylureido)-N-(thiazol-2-yl)benzenesulphonamide showed the highest activity. Its minimum inhibitory concentrations (MIC) against Mycobacterium tuberculosis My 331/88 (4 µmol/l) were superior to those obtained for sulphathiazole. In the case of nontuberculous mycobacteria (M. avium My 330/88, M. kansasii My 235/88 and M. kansasii My 6509/96), their activities were comparable (≥ 2 µmol/l). Amides showed also a significant antimycobacterial activity, especially against M....
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