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Growth and control of Pseudomonas aeruginosa in a multi-species biofilm
Hutlas, Andrej ; Kučerová, Marta (advisor) ; Konečná, Klára (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Cardiff University, School of Pharmacy and Pharmaceutical Sciences Study program: Pharmacy Candidate: Andrej Hutlas Consultants: PharmDr. Marta Kučerová, Ph.D. (Charles); Prof. Jean-Yves Maillard (Cardiff); BSc. Katarzyna Ledwoch Ph.D. (Cardiff) Biofilms are a default mode of growth for most bacteria. Microbes encapsulate themselves within a matrix, composed mainly of extracellular polymeric substances. A biofilm can be composed by multiple species. Matrix environment induces various physiological shifts, such as switch to dormant state or expression of biofilm-specific genes. Mature biofilm's heterogeneous, due to differences in spatial microbe distribution and spatial nutrient utilization across the matrix. Matrix provides many advantages to bacteria, like nutrient capture and transfer or protection against extreme conditions. Washbasin U-bend multi-species biofilms were investigated with a special focus on Pseudomonas aeruginosa. This opportunistic pathogen causes nosocomial infections, mainly in immunocompromised patients, with considerable health and socio-economic impacts. A link between sinks and environmental P. aeruginosa contamination has been established. Environmental decontamination may be an approach to lessen aforementioned...
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Growth and control of Pseudomonas aeruginosa in a multi-species biofilm
Hutlas, Andrej ; Kučerová, Marta (advisor) ; Konečná, Klára (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Cardiff University, School of Pharmacy and Pharmaceutical Sciences Study program: Pharmacy Candidate: Andrej Hutlas Consultants: PharmDr. Marta Kučerová, Ph.D. (Charles); Prof. Jean-Yves Maillard (Cardiff); BSc. Katarzyna Ledwoch Ph.D. (Cardiff) Biofilms are a default mode of growth for most bacteria. Microbes encapsulate themselves within a matrix, composed mainly of extracellular polymeric substances. A biofilm can be composed by multiple species. Matrix environment induces various physiological shifts, such as switch to dormant state or expression of biofilm-specific genes. Mature biofilm's heterogeneous, due to differences in spatial microbe distribution and spatial nutrient utilization across the matrix. Matrix provides many advantages to bacteria, like nutrient capture and transfer or protection against extreme conditions. Washbasin U-bend multi-species biofilms were investigated with a special focus on Pseudomonas aeruginosa. This opportunistic pathogen causes nosocomial infections, mainly in immunocompromised patients, with considerable health and socio-economic impacts. A link between sinks and environmental P. aeruginosa contamination has been established. Environmental decontamination may be an approach to lessen aforementioned...
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Synthesis of thiazolidine-2,4-dione derivatives as potential drugs I
Dušková, Anna ; Kučerová, Marta (advisor) ; Zitko, Jan (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Title of diploma thesis: Synthesis of thiazolidine-2,4-dione derivatives as potential drugs I Student: Anna Dušková Supervisor: PharmDr. Marta Kučerová, Ph.D. The theoretical part of this diploma thesis summarizes the biological activity of thiazolidine- 2,4-dione derivatives, focused mainly on their antibacterial, antimycobacterial and antifungal effects. The theoretical part shows that thiazolidine-2,4-dione derivatives are substances that have great potential to become good candidates for new drugs that are needed to be obtained due to the growing bacterial resistance to existing drugs. Thiazolidine-2,4-dione derivatives are already used in clinical practice as oral antidiabetics - pioglitazone and rosiglitazone. In the experimental part, I dealt with a three-step synthesis of (2,4-dioxothiazolidin-3-yl) acetic acid derivatives, which, however, was not succesful to prepare except for one product. This was followed by the synthesis of thiazolidine-2,4-dione derivatives, which consisted of the Knoevenagel condensation of thiazolidine-2,4-dione with aromatic and heterocyclic aldehydes, in which we managed to obtain a total of eight products. All substances were characterized...
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Synthesis and evaluation of probes for fluorescent microscopy based on cyanopyridines and merocyanine scaffolds and lanthanide complexes
Bajnok, Juraj ; Kučerová, Marta (advisor) ; Zimčík, Petr (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Student: Juraj Bajnok Supervisor: PharmDr. Marta Kučerová, Ph.D. Consultant: Assist. prof. Stane Pajk, M. Pharm., Ph.D. Title of diploma thesis: Synthesis and evaluation of probes for fluorescent microscopy based on cyanopyridines and merocyanine scaffolds and lanthanide complexes Fluorescence as part of luminescence is a process, which describes how electrons of suitable materials are excited by the energy absorption of a photon, followed by the immediate emission of a photon with less energy compared to the absorbed photon. Suitable compounds must contain a system of conjugated double bonds. In this thesis, we present the synthesis and evaluation of fluorescence on derivates of cyanopyridines, merocyanine-type fluorescent probes, and lanthanide complexes of terbium, dysprosium, and europium. Lanthanide ions have low molar extinction coefficients, therefore they cannot be excited directly, without a proper ligand. We explored the influence of pH on the emission of synthesized derivates of cyanopyridines. We synthesized two merocyanine dyes with new alkyl moieties, which should change their emission spectra. Then, the merocyanine dyes could serve as new fluorescent probes for...
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Amaryllidaceae alkaloids as inspiration for preparation of selective butyrylcholinesterase inhibitors I
Wisura, Matěj ; Cahlíková, Lucie (advisor) ; Kučerová, Marta (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Botany Candidate: Matěj Wisura Supervisor: prof. Ing. Lucie Cahlíková, Ph.D. Title of diploma thesis: Amaryllidaceae alkaloids as inspiration for preparation of selective butyrylcholinesterase inhibitors I The Amaryllidaceae family is considered to be very important source of biologicaly active natural compounds, alkaloids. These compounds are intensively studied because of their antiviral, antifungal, antiparasitic, antioxidative and antiinflammatory properties and especially for their ability to inhibit cholinesterases. This source is still not entirely depleted, which is proved by recent isolation of utterly new structural type of Amaryllidaceae alkaloids, carltonines, isolated form Narcissus pseudonarcissus cv. Carlton. Carltonines have shown promissing inhibitory activity of BuChE. Isolation of carltonines has become an inspiration for synthesis of highly selective BuChE inhibitors based on norbelladine structural type. This diploma thesis proceeds from pilot series of 20 compounds. During this study, another 21 compounds were prepared, expanding the portfolio and knowledge of structure-activity relationships within selective BuChE inhibitors group. Generated compounds were identified using NMR and ESI-HRMS....
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Synthesis and evaluation of probes for fluorescent microscopy based on cyanopyridines and merocyanine scaffolds and lanthanide complexes
Bajnok, Juraj ; Kučerová, Marta (advisor) ; Zimčík, Petr (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Student: Juraj Bajnok Supervisor: PharmDr. Marta Kučerová, Ph.D. Consultant: Assist. prof. Stane Pajk, M. Pharm., Ph.D. Title of diploma thesis: Synthesis and evaluation of probes for fluorescent microscopy based on cyanopyridines and merocyanine scaffolds and lanthanide complexes Fluorescence as part of luminescence is a process, which describes how electrons of suitable materials are excited by the energy absorption of a photon, followed by the immediate emission of a photon with less energy compared to the absorbed photon. Suitable compounds must contain a system of conjugated double bonds. In this thesis, we present the synthesis and evaluation of fluorescence on derivates of cyanopyridines, merocyanine-type fluorescent probes, and lanthanide complexes of terbium, dysprosium, and europium. Lanthanide ions have low molar extinction coefficients, therefore they cannot be excited directly, without a proper ligand. We explored the influence of pH on the emission of synthesized derivates of cyanopyridines. We synthesized two merocyanine dyes with new alkyl moieties, which should change their emission spectra. Then, the merocyanine dyes could serve as new fluorescent probes for...
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Synthesis of a combinatorial compound library based on the double click reaction
Krutáková, Mária ; Zitko, Jan (advisor) ; Kučerová, Marta (referee)
(English) Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Author: Mária Krutáková Supervisor: Assoc. Prof. PharmDr. Jan Zitko, Ph.D. Title: Synthesis of a combinatorial compound library based on the double click reaction Click chemistry is a powerful tool in drug discovery. It is very efficient in creating compound libraries through the combinatorial methodology. The copper(I)-catalyzed 1,2,3-triazole- forming reaction between azides and terminal alkynes has become the gold standard of click chemistry due to high reaction efficiency, mild reaction conditions, chemo- and regioselectivities. The molecules with triazole moiety display a broad spectrum of favorable properties and have been used in the development of antibacterial, antiviral, anti-inflammatory, anticancer, and anti-tubercular agents. This work focused on preparing a compound library using double-click reactions. Firstly, we synthesized several compounds with two alkyne groups ("alkyne cores") and a diverse group of structurally simple azides. In the next step, one equivalent of alkyne core was reacted with two equivalents of all prepared azides. The reaction between each alkyne core and ten azides yielded 100 compounds. The prepared libraries of compounds were...
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Amaryllidaceae alkaloids as inspiration for preparation of selective butyrylcholinesterase inhibitors I
Wisura, Matěj ; Cahlíková, Lucie (advisor) ; Kučerová, Marta (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Botany Candidate: Matěj Wisura Supervisor: prof. Ing. Lucie Cahlíková, Ph.D. Title of diploma thesis: Amaryllidaceae alkaloids as inspiration for preparation of selective butyrylcholinesterase inhibitors I The Amaryllidaceae family is considered to be very important source of biologicaly active natural compounds, alkaloids. These compounds are intensively studied because of their antiviral, antifungal, antiparasitic, antioxidative and antiinflammatory properties and especially for their ability to inhibit cholinesterases. This source is still not entirely depleted, which is proved by recent isolation of utterly new structural type of Amaryllidaceae alkaloids, carltonines, isolated form Narcissus pseudonarcissus cv. Carlton. Carltonines have shown promissing inhibitory activity of BuChE. Isolation of carltonines has become an inspiration for synthesis of highly selective BuChE inhibitors based on norbelladine structural type. This diploma thesis proceeds from pilot series of 20 compounds. During this study, another 21 compounds were prepared, expanding the portfolio and knowledge of structure-activity relationships within selective BuChE inhibitors group. Generated compounds were identified using NMR and ESI-HRMS....
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Synthesis of thiazolidin-2,4-dione derivatives as potential drugs III
Fontánová, Karolína ; Kučerová, Marta (advisor) ; Zitko, Jan (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Title of diploma thesis: Synthesis of thiazolidine-2,4-dione derivatives as potential drugs III Student: Karolína Fontánová Supervisor: PharmDr. Marta Kučerová, Ph.D. The theoretical part is focused on the biological activity of thiazolidine-2,4-dione (TZD) derivatives, especially on their antibacterial (including antimycobacterial) and antifungal effects. The cited literature shows that in many cases the presence of an aromatically substituted thiazolidine-2,4-dione nucleus in the molecule conditions antimicrobial activity. TZD derivatives seem to be suitable candidates for the development of new drugs. In the experimental part molecular docking of a series of 5-(hetero)arylmethylidenethiazolidine-2,4-diones, including the substances synthesized by us, was performed into the MurD ligase of E. coli. Furthermore eleven syntheses of 5-(hetero)arylmethylidenethiazolidine-2,4-diones were performed using Knoevenagel condensation of TZD with (hetero)aromatic aldehydes. Ten products were successfully synthesized and were characterized by melting points, NMR, IR, and MS spectra, and their purity was verified by accomplishment of elemental analysis. The obtained substances were tested...
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Synthesis of new antimitotic agents
Hoppová, Martina ; Kučerová, Marta (advisor) ; Miletín, Miroslav (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Student: Martina Hoppová Supervisors: PharmDr. Marta Kučerová, Ph.D.; Dr. Rafael Peláez Lamamie de Clairac Arroyo Title of diploma thesis: Synthesis of new antimitotic agents Cancer is one of the main causes of death all around the world and therefore the development of new chemotherapeutic drugs is one of the major areas of pharmaceutical research. The effort is to obtain an agent that would be highly effective, target the neoplastic tissue, and have advantageous pharmacological properties and minimum side effects. Rapid proliferation is one of the main features of cancerous growth, thus influencing mitosis as the phase of cell division may be a convenient way for cancer treatment. Tubulin is a protein, which rapidly polymerizes into microtubules and again depolymerizes and beside others it forms mitotic spindle during mitosis, and according to its important role, tubulin is an attractive target for antitumoral agents. Many drugs inhibiting polymerization or stabilizing already formed microtubules are actually in clinical practice, and research regarding new antimitotics interacting with tubulin is going on at the same time. Such an example is natural combretastatin A-4...
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