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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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Synthesis of novel 5,6-disubstituted derivatives of uracil as potential drugs
Vu, Lien Phuong ; Kučerová, Marta (advisor) ; Zimčík, Petr (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Candidate: Vu Lien Phuong Supervisors: PharmDr. Marta Kučerová, Ph.D. Tanja Bruun, M.Sc. (Pharm.) Prof. Jari Yli-Kauhaluoma Title of diploma thesis: Synthesis of novel 5,6-disubstituted derivatives of uracil as potential drugs In this thesis, uracil was used as the core structure given its many biological activities that were reported such as antitumor, antiviral, antibiotic, hypoglycemic, diuretic and many others. The work was focused on the preparation of new 5,6- disubstituted uracil derivatives as potential biologically active agents. 2,4,6-Trichloropyrimidine was used for the preparation of 6-chlorouracil that was condensed with phenols or anilines to give the respective 6-phenoxyuracils and 6- phenylaminouracils. These intermediates were then modified in position 5 to give the final products. For this very challenging last step, various alkylating and acylating agents were used, e.g. Vilsmeier reagent, alkylchlorides, chloroacetyl chloride, ethyl chlorooxoacetate and ethyl bromoacetate. In the end, ethyl bromoacetate gave the most promising results affording four novel 5,6-disubstituted uracil derivatives. During the experimental work it was found that pH of water used...
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Synthesis and study of supramolecular properties of azaphthalocyanines usable as sensors
Sikorová, Eliška ; Demuth, Jiří (advisor) ; Kučerová, Marta (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Candidate Eliška Sikorová Supervisor PharmDr. Jiří Demuth, Ph.D. Title of ThesisSynthesis and study of supramolecular properties of azaphthalocyanines usable as sensors Azaphthalocyanines are planar aromatic macrocycles that were derived from natural porphyrins. The basic skeleton consists of four isoindole units which are linked at positions 1 and 3 by azamethine bridges, resulting in an extensive system of conjugated double bonds that give these compounds unique optical and electrical properties. Azaphthalocyanines are widely used as industrial dyes, conductors, photosensitizers in photodynamic therapy, fluorescence quenchers or fluorescence sensors, etc. The compounds synthesized during this thesis can be used as an interesting type of sensors for sensing coordination analytes in solution. That is why this work deals with the study of the supramolecular properties of the synthesized compounds, in particular the ability to form J-dimer type aggregates, which are formed by coordination of the peripheral pyridyl nitrogen to the central zinc cation of the second azapthalocyanine. J-dimers resemble a "step-like" arrangement in contrast to the second type of...
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Synthesis of thiazolidine derivatives as potential drugs
Makovská, Kateřina ; 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 derivatives as potential drugs Student: Kateřina Makovská Supervisor: PharmDr. Marta Kučerová, Ph.D. The theoretical part was focused on the literature research on the biological activity of derivatives 2-thioxothiazolidine-4-one (rhodanine) and its oxygen isostere thiazoli- dine-2,4-dione. There was mainly the antibacterial, antimycobacterial, and antifungal activity of variously substituted rhodanine and thiazolidine-2,4-dione derivatives repor- ted. These derivatives seem to be suitable candidates for the development of new drugs Within the experimental part, an in silico study on molecular docking of a larger series of rhodanine and thiazolidine-2,4-dione derivatives prepared in this work and earlier was performed with MurD ligase of E. coli as a potential bacterial target. On the whole, seventeen syntheses were performed in the laboratory using the Kno- evenagel condensation of thiazolidine-2,4-dione or rhodanine with various aldehydes, nine reactions with the aim to obtain thiazolidine-2,4-dione derivatives and eight reacti- ons withe the goal to get rhodanine derivatives. Eleven reactions afforded successfully six...
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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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