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Compounds combining pyrazinamide and p-aminosalicylic acid fragments as potential antituberculars II
Žák, Ondřej ; Zitko, Jan (advisor) ; Miletín, Miroslav (referee)
COMPOUNDS COMBINING PYRAZINAMIDE AND P-AMINOSALICYLIC ACID FRAGMENTS AS POTENTIAL ANTITUBERCULARS II ŽÁK ONDŘEJ Department of Pharmaceutical Chemistry and Drug Analysis, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic A series of new compounds combining pyrazinamide and p-aminobenzoic acid was prepared and in vitro tested for antimycobacterial activity against M. tuberculosis, M. avium, M. kansasii, M. aurum and M. smegmatis. Previously prepared 4-(5-chloropyrazine-2-carboxamido)-2-hydroxybenzoic acid (R1 = OH) exerted micromolar activity against M.tuberculosis and low in vitro cytotoxicity in HepG2 cells. Para-Aminosalicylic acid (PAS) has significant antitubercular properties based on its resemblance to p-aminobenzoic acid and interference with the folate pathway in mycobacteria. To assess the role of the PAS fragment, we designed and prepared derivatives with modified substitution on the phenyl ring (R1 ). Further modification was the exchange of 5-Cl on the pyrazine core for (alkyl)amino substituent (JZ-OZ), which was a successful modification in previous series. Final compounds were described by melting point, elementary analysis, IR spectroscopy and 1 H, 13 C NMR. Changing the PAS fragment, when we removed or replaced the OH-group at position 2, the antimycobacterial...
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Compounds combining pyrazinamide and 4-aminobenzoic acid fragments as potential antituberculars
Žecová, Jana ; Zitko, Jan (advisor) ; Zimčík, Petr (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical chemistry and Pharmaceutical analysis Author: Jana Žecová Supervisor: PharmDr. Jan Zitko, Ph.D. Title of diploma thesis: Compounds combining pyrazinamide and 4-aminobenzoic acid fragments as potential antituberculars Tuberculosis is a severe infectious disease, which has been afflicting the human world population for centuries. It's figuring in the scale of the deadliest diseases as well as the occurring of strains resistant to therapy requires a serious approach to this problem and the research of new therapeutic means. Among the actual antituberculars figure two compounds, PZA and PAS. Pyrazinamide is a first line drug, and its derivatives are subject of the research in the Department of Pharmaceutical chemistry and Pharmaceutical analysis. Structurally similar to 4-aminobenzoic acid, PAS is a second line antitubercular, which is again actual in the therapy of resistant form of TBC. This diploma thesis treats about possibilities of the use of compounds combining fragments of PZA and 4-aminobenzoic acid as potential antituberculars. Furthermore, this thesis evaluates the influence of PAS fragment in the derivatives prepared with this antimycobacterial purpose. The theoretical part describes the actual state of...
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Compounds combining pyrazinamide and 4-aminobenzoic acid fragments as potential antituberculars
Žecová, Jana ; Zitko, Jan (advisor) ; Zimčík, Petr (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical chemistry and Pharmaceutical analysis Author: Jana Žecová Supervisor: PharmDr. Jan Zitko, Ph.D. Title of diploma thesis: Compounds combining pyrazinamide and 4-aminobenzoic acid fragments as potential antituberculars Tuberculosis is a severe infectious disease, which has been afflicting the human world population for centuries. It's figuring in the scale of the deadliest diseases as well as the occurring of strains resistant to therapy requires a serious approach to this problem and the research of new therapeutic means. Among the actual antituberculars figure two compounds, PZA and PAS. Pyrazinamide is a first line drug, and its derivatives are subject of the research in the Department of Pharmaceutical chemistry and Pharmaceutical analysis. Structurally similar to 4-aminobenzoic acid, PAS is a second line antitubercular, which is again actual in the therapy of resistant form of TBC. This diploma thesis treats about possibilities of the use of compounds combining fragments of PZA and 4-aminobenzoic acid as potential antituberculars. Furthermore, this thesis evaluates the influence of PAS fragment in the derivatives prepared with this antimycobacterial purpose. The theoretical part describes the actual state of...
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Compounds combining pyrazinamide and 4-aminobenzoic acid fragments as potential antituberculars
Žecová, Jana ; Zitko, Jan (advisor) ; Zimčík, Petr (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical chemistry and Pharmaceutical analysis Author: Jana Žecová Supervisor: PharmDr. Jan Zitko, Ph.D. Title of diploma thesis: Compounds combining pyrazinamide and 4-aminobenzoic acid fragments as potential antituberculars Tuberculosis is a severe infectious disease, which has been afflicting the human world population for centuries. It's figuring in the scale of the deadliest diseases as well as the occurring of strains resistant to therapy requires a serious approach to this problem and the research of new therapeutic means. Among the actual antituberculars figure two compounds, PZA and PAS. Pyrazinamide is a first line drug, and its derivatives are subject of the research in the Department of Pharmaceutical chemistry and Pharmaceutical analysis. Structurally similar to 4-aminobenzoic acid, PAS is a second line antitubercular, which is again actual in the therapy of resistant form of TBC. This diploma thesis treats about possibilities of the use of compounds combining fragments of PZA and 4-aminobenzoic acid as potential antituberculars. Furthermore, this thesis evaluates the influence of PAS fragment in the derivatives prepared with this antimycobacterial purpose. The theoretical part describes the actual state of...
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Compounds combining pyrazinamide and p-aminosalicylic acid fragments as potential antituberculars II
Žák, Ondřej ; Zitko, Jan (advisor) ; Miletín, Miroslav (referee)
COMPOUNDS COMBINING PYRAZINAMIDE AND P-AMINOSALICYLIC ACID FRAGMENTS AS POTENTIAL ANTITUBERCULARS II ŽÁK ONDŘEJ Department of Pharmaceutical Chemistry and Drug Analysis, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic A series of new compounds combining pyrazinamide and p-aminobenzoic acid was prepared and in vitro tested for antimycobacterial activity against M. tuberculosis, M. avium, M. kansasii, M. aurum and M. smegmatis. Previously prepared 4-(5-chloropyrazine-2-carboxamido)-2-hydroxybenzoic acid (R1 = OH) exerted micromolar activity against M.tuberculosis and low in vitro cytotoxicity in HepG2 cells. Para-Aminosalicylic acid (PAS) has significant antitubercular properties based on its resemblance to p-aminobenzoic acid and interference with the folate pathway in mycobacteria. To assess the role of the PAS fragment, we designed and prepared derivatives with modified substitution on the phenyl ring (R1 ). Further modification was the exchange of 5-Cl on the pyrazine core for (alkyl)amino substituent (JZ-OZ), which was a successful modification in previous series. Final compounds were described by melting point, elementary analysis, IR spectroscopy and 1 H, 13 C NMR. Changing the PAS fragment, when we removed or replaced the OH-group at position 2, the antimycobacterial...
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Compounds combining pyrazinamide and p-aminosalicylic acid fragments as potential antituberculars II
Žák, Ondřej ; Zitko, Jan (advisor) ; Miletín, Miroslav (referee)
COMPOUNDS COMBINING PYRAZINAMIDE AND P-AMINOSALICYLIC ACID FRAGMENTS AS POTENTIAL ANTITUBERCULARS II ŽÁK ONDŘEJ Department of Pharmaceutical Chemistry and Drug Analysis, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic A series of new compounds combining pyrazinamide and p-aminobenzoic acid was prepared and in vitro tested for antimycobacterial activity against M. tuberculosis, M. avium, M. kansasii, M. aurum and M. smegmatis. Previously prepared 4-(5-chloropyrazine-2-carboxamido)-2-hydroxybenzoic acid (R1 = OH) exerted micromolar activity against M.tuberculosis and low in vitro cytotoxicity in HepG2 cells. Para-Aminosalicylic acid (PAS) has significant antitubercular properties based on its resemblance to p-aminobenzoic acid and interference with the folate pathway in mycobacteria. To assess the role of the PAS fragment, we designed and prepared derivatives with modified substitution on the phenyl ring (R1 ). Further modification was the exchange of 5-Cl on the pyrazine core for (alkyl)amino substituent (JZ-OZ), which was a successful modification in previous series. Final compounds were described by melting point, elementary analysis, IR spectroscopy and 1 H, 13 C NMR. Changing the PAS fragment, when we removed or replaced the OH-group at position 2, the antimycobacterial...
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Compounds combining pyrazinamide and 4-aminobenzoic acid fragments as potential antituberculars
Žecová, Jana ; Zitko, Jan (advisor) ; Zimčík, Petr (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical chemistry and Pharmaceutical analysis Author: Jana Žecová Supervisor: PharmDr. Jan Zitko, Ph.D. Title of diploma thesis: Compounds combining pyrazinamide and 4-aminobenzoic acid fragments as potential antituberculars Tuberculosis is a severe infectious disease, which has been afflicting the human world population for centuries. It's figuring in the scale of the deadliest diseases as well as the occurring of strains resistant to therapy requires a serious approach to this problem and the research of new therapeutic means. Among the actual antituberculars figure two compounds, PZA and PAS. Pyrazinamide is a first line drug, and its derivatives are subject of the research in the Department of Pharmaceutical chemistry and Pharmaceutical analysis. Structurally similar to 4-aminobenzoic acid, PAS is a second line antitubercular, which is again actual in the therapy of resistant form of TBC. This diploma thesis treats about possibilities of the use of compounds combining fragments of PZA and 4-aminobenzoic acid as potential antituberculars. Furthermore, this thesis evaluates the influence of PAS fragment in the derivatives prepared with this antimycobacterial purpose. The theoretical part describes the actual state of...
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