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Design, synthesis and evaluation of heterocyclic compounds with potential antimicrobial activity I
Brányik, Michal ; Zitko, Jan (advisor) ; Demuth, Jiří (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Title of the thesis: Design, synthesis and evaluation of heterocyclic compounds with potential antimicrobial activity I Author: Michal Brányik Supervisor: doc. PharmDr. Jan Zitko, Ph.D. Consultant: PharmDr. Martin Juhás, Ph.D. Antimicrobial resistance is an ever-growing problem that occurs worldwide. Many bacterial strains develop the ability to resist the otherwise efficient substances, thus posing a serious threat for the future. Mycobacterium tuberculosis (Mtb), the source of tuberculosis, is no exception. Given that it is the leading cause of death due to a single pathogen, many efforts have been put into finding new active compounds. The substances synthesized as a part of this thesis are based on previously prepared substances with potential antimicrobial activity. The basic structure consists of 2-aminooxazole or 2-aminothiazole and substituted pyridine or pyrazine carboxamides. The structures were confirmed by the 1 H and 13 C NMR spectra, IR spectra and mass spectrometry. All the substances were tested for in vitro activity against eight bacterial strains (four gram-positive and four gram-negative) as well as eight fungal strains (four yeast and four fungi). We also...
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Design, synthesis and evaluation of heterocyclic compounds with potential antimicrobial activity VI
Abdalrahman, Nechirwan Taimur ; Zitko, Jan (advisor) ; Nováková, Veronika (referee)
(In English) Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Author: Nechirwan Abdalrahman Supervisor: Assoc. Prof. PharmDr. Jan Zitko, Ph.D. Title: Design, synthesis, and evaluation of heterocyclic compounds with potential antimicrobial activity VI Despite the existence of a well-established treatment regimens, tuberculosis (TB) continues to be the most leading cause of death by a single microorganism, as reported by WHO. One of the reasons behind treatment failure in completely eradicating this infection is drug resistance. Novel 3-(phenylureido)pyrazine-2-carboxamide derivatives, refer to figure below, were synthesized by reacting 3-chloropyrazine-2-carboxamide with ammonia to produce 3- aminopyrazine-2-carboxamide as an intermediate building block, followed by reacting with various substituted phenyl isocyanates using a microwave reactor. The synthesized compounds were evaluated for in vitro activity against various mycobacterial strains, where most active ones among them showed moderate to low activities; 4-tertiary butyl (MIC 62.5 µg/mL), 4-NO2 (MIC 62.5 µg/mL), 4-Bromo (MIC 250 µg/mL), 4-Cl (MIC 250 µg/mL), 2-F (MIC 250 µg/mL), and non-substituted (MIC 500 µg/mL). As a complementary study in silico, the synthesized...
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Design, synthesis and evaluation of heterocyclic compounds with potential antimicrobial activity IV
Fekri, Amir Hossein ; Zitko, Jan (advisor) ; Miletín, Miroslav (referee)
(English) Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Thesis title: Design, synthesis and evaluation of heterocyclic compounds with potential antimicrobial activity IV Candidate: Amirhossein Fekri Supervisor: doc. PharmDr. Jan Zitko, Ph.D. Consultant: Mgr. Vinod S. K. Pallabothula Tuberculosis has remained one of the deadliest infectious diseases worldwide caused by a single infectious agent, the rapid growth of resistance to anti-tubercular drugs hinders the successful control and treatment of TB worldwide, which challenges the scientific community to develop new drugs to improve currently available treatment. This diploma thesis represents the design, synthesis, and biological evaluation of two series of compounds including cyclized (pyrazine- oxazinone) and carboxamide derivatives as potentially active antimycobacterial agents sharing a pyrazine core as common structural features that could potentially target mycobacterial aspartate decarboxylase (PanD) and prolyl-tRNA synthetase (mtProRS), respectively. Synthesis of final compounds was achieved through individual reaction steps involving acylation of methyl 3-aminopyrazine-2-carboxylate for preparation of a common intermediate which in turn was used for the...
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Design, synthesis and evaluation of heterocyclic compounds with potential antimicrobial activity I
Brányik, Michal ; Zitko, Jan (advisor) ; Demuth, Jiří (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Title of the thesis: Design, synthesis and evaluation of heterocyclic compounds with potential antimicrobial activity I Author: Michal Brányik Supervisor: doc. PharmDr. Jan Zitko, Ph.D. Consultant: PharmDr. Martin Juhás, Ph.D. Antimicrobial resistance is an ever-growing problem that occurs worldwide. Many bacterial strains develop the ability to resist the otherwise efficient substances, thus posing a serious threat for the future. Mycobacterium tuberculosis (Mtb), the source of tuberculosis, is no exception. Given that it is the leading cause of death due to a single pathogen, many efforts have been put into finding new active compounds. The substances synthesized as a part of this thesis are based on previously prepared substances with potential antimicrobial activity. The basic structure consists of 2-aminooxazole or 2-aminothiazole and substituted pyridine or pyrazine carboxamides. The structures were confirmed by the 1 H and 13 C NMR spectra, IR spectra and mass spectrometry. All the substances were tested for in vitro activity against eight bacterial strains (four gram-positive and four gram-negative) as well as eight fungal strains (four yeast and four fungi). We also...
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