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Design, synthesis and evaluation of heterocyclic compounds with potential antimicrobial activity VI
Abdalrahman, Nechirwan ; 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 V
Askari, Asal ; Zitko, Jan (advisor) ; Zimčík, Petr (referee)
(CZECH) Univerzita Karlova, Farmaceutická fakulta v Hradci Králové, Katedra farmaceutické chemie a farmaceutické analýzy Řešitel: Asal Askari Vedoucí diplomové práce: doc. PharmDr. Jan Zitko, Ph.D. Konzultant: Ghada Bouz, Ph.D. Název diplomové práce: Návrh, syntéza a hodnocení heterocyklických sloučenin s potenciální antimikrobní aktivitou V Staphylococcus aureus (SA) je jednou z nejčastějších příčin život ohrožujících infekcí. Jedním ze způsobů, jak kontrolovat infekčnost SA, je vývoj inovativních látek, nejlépe s novým mechanismem účinku, které jsou účinné jak proti kmenům citlivým na léky, tak proti kmenům lékově rezistentním. Chinazolon slouží jako základní kostra pro mnoho různých biologicky aktivních sloučenin. Antistafylokokové chinazolony (AQs) mají v literatuře popsané vztahy mezi strukturou a aktivitou. Penicilin vázající protein (PBP), DNA topoizomeráza a laktátdehydrogenáza jsou některé z molekulárních cílů pro AQs. S využitím in silico molekulového dokování jsme spojili naše rozsáhlé znalosti antibakteriálních léčiv s tím, co bylo popsáno v literatuře, abychom vytvořili nové, potenciálně aktivní AQs zaměřené na PBP. Výsledkem bylo, že jsme připravili 11 finálních sloučenin s lipofilitou v rozmezí 2,69 až 4,06 reakcí laktonového meziproduktu, benzoxazinonu, s různými benzylaminy....
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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 III
Rahi, Fahim - Joe ; Zitko, Jan (advisor) ; Kučerová, Marta (referee)
Univerzita Karlova Farmaceutická fakulta v Hradci Králové Katedra farmaceutické chemie a farmaceutické analýzy Kandidát: Fahim Joe Rahi Vedoucí: doc. PharmDr. Jan Zitko, Ph.D. Název diplomové práce: Návrh, syntéza a hodnocení heterocyklických sloučenin s potenciální antimikrobní aktivitou III Nadužívání antibiotik vedlo k alarmujícímu nárůstu rezistence. Akutní potřeba antibiotik s novým mechanismem účinku vedla náš výzkum k nalezení slibných nových sloučenin prostřednictvím studie HIT-SAR. Cílená struktura byla inspirována nedávnou publikací. Naše sloučeniny mají navíc methylenový můstek mezi heterocyklem a benzenovým kruhem. Tento methylenový můstek zvyšuje flexibilitu struktury, což může zlepšit interakční potenciál sloučenin. Obecně lze říci, že methylenový můstek nezlepšil antimikrobiální vlastnosti zamýšlených sloučenin. V některých případech byla antimikrobiální aktivita významně snížena ve srovnání s publikovanými sloučeninami. MIC nebyla dostatečná k provedení dalšího mikrobiologického testování.
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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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Porous hydrogels from natural gum modified with bio-active substances for accelerated wound healing
Černá, Eva ; Brtníková, Jana (referee) ; Vojtová, Lucy (advisor)
Hlavní téma této diplomové práce se zaměřuje na navržení, přípravu a optimalizaci složení hydrogelového krytu ran s vlastnostmi podobnými kůži. Finančně nenáročný hydrogelový kryt s vlastnostmi, který podporuje proces hojení, zabraňuje bakteriální infekci a snadná manipulace, je myšleným výsledkem této práce. Teoretická část je zaměřena na charakterizaci jednotlivých vrstev kůže, polymerní materiály vhodné pro léčbu ran, aditiva které podporují hojení a mají antimikrobiální vlastnosti, které tvoří aseptické prostředí v ráně. Experimentální práce zahrnuje několik kroků. Prvním z nich je optimalizace složení hydrogelového krytu ran složeného z přírodního polymeru, pryskyřice Gum Karaya (GK) modifikovaného se syntetickými hydrofilními gelujícími polymery a důležitou změkčující složkou pro získání měkkého, elastického a transparentního materiálu získaného metodou sušení, lyofilizace. Připravené filmy byly testování z hlediska botnání, hydrolitické stability, transparentnosti, pevnost v tahu v suchém i mokrém stavu, chemické složení a morfologie. Druhý krok zahrnoval integraci bioaktivního antiseptika do struktury hydrogelu, který zajišťuje vhodné antimikrobiální podmínky pro hojení ran. Připravené transparentní, hydrolyticky stabilní filmy se ukázaly být efektivní proti oběma testovaným druhům bakteriálních kmenů, gram-pozitivním i gram-negativním, mezi které patřily: Staphylococcus aureus methicillin-senzitivní, Staphylococcus aureus methicillin-rezistentní, Staphylococcus epidermidis, Klebsiella pneumoniae, Enterobacter cloacae, Enterococcus faecalis, Pseudomonas aeruginosa, Candida albicans and Escherichia coli. Následná práce bude zaměřena na testování in vitro a in vivo testy biocompatibility.
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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 pyridine derivatives as potential antimicrobial compounds
Bachtíková, Andrea ; Zitko, Jan (advisor) ; Demuth, Jiří (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Thesis title: Design, synthesis and evaluation of pyridine derivatives as potential antimicrobial compounds Author: Andrea Bachtíková Thesis supervisor: doc. PharmDr. Jan Zitko, Ph.D. Consultant: PharmDr. Martin Juhás Tuberculosis is a global problem even today. It is the second most common cause of death from infectious diseases according to the WHO and resistance to common antituberculosis drugs, which have been used in therapy for decades, increases. These facts are the main reasons why research into new potential drugs is needed. This thesis presents design, synthesis and evaluation of antimicrobial properties of a series of substituted N-oxazolyl and N-thiazolyl carboxamides of different pyridinecarboxylic acids. Final compounds were characterized by 1 H and 13 C-NMR spectroscopy, IR spectra, melting point and HRMS (High resolution mass spectrometry). Obtained compounds were tested for in vitro activity against M. tuberculosis H37Rv, M. tuberculosis H37Ra and four other clinically less important mycobacterial strains. In addition, compounds were tested for antibacterial activity against four G+ and four G- bacterial strains, antifungal activity against yeasts and fungi,...
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