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Synthesis and evaluation of potential antitubercular agents based on nitro aromates
Delong, Jakub ; Krátký, Martin (advisor) ; Kučerová, Marta (referee)
The goal of the master's thesis was the synthesis and assessment of potential molecules against tuberculosis based on aromatic compounds containing nitro groups. The thesis reviews tuberculosis and its therapy, in the theoretical part, followed by well-know and new nitro group containing antibiotics. The experimental part reports multitep synthesis from parent compounds - substituted benzoic acid, pyruvic acid and variously substituted anilines, which were evaluated for their antimycobacterial activity. The core structure of the prepared compound molecules is N-phenyl-2-[2-(3,5- dinitrobenzoyl)hydrazinylidene]propanamide, which was variously substituted on the benzene ring of N-phenylpropanamide. In case of four compounds, one nitro group was switched to the trifluoromethyl group. Yields varied from 7 to 72 % and their minimum inhibitory concentrations (MIC) ranged from 4 to more than 1000 µmol/l. N-(4-Bromphenyl)-2-[2-(3,5- dinitrobenzoyl)hydrazinylidene]propanamide proved to be the most effective derivate. Key words Antibiotics, antimycobacterial activity, 3,5-dinitrobenzohydrazide, nitro group, synthesis, tuberculosis
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Synthesis and investigation of potential antimicrobial compounds
Pokorná, Anežka ; Krátký, Martin (advisor) ; Zitko, Jan (referee)
One of the ways to alleviate the global problem of antibiotic resistance is, among other things, the synthesis and development of new antimicrobials. All compounds prepared in this work are based on the molecule 4-amino-1-benzylpiperidine or its isomer 4-(piperidin-1- ylmethyl)aniline. The parent molecule was chosen on the based on its previously reported activity. Thirteen imines were prepared using one-step synthesis by reacting the starting amine with the corresponding aldehyde. Two additional syntheses led to the amides by reaction of the starting molecule with the corresponding salicylic acid. The yields of the reactions ranged from 26 to 97 % for the imines and were 25 and 39 % for the amides. All compounds were prepared in sufficient quantity and purity to determine biological activity. All fifteen compounds were tested for their antibacterial activity against clinically relevant Gram-positive and Gram-negative strains. They were further tested for their antifungal activity, antimycobacterial aktivity, and their ability to inhibit the enzymes acetylcholinesterase and butyrylcholinesterase was also tested. The results of the evaluation showed that the amides were ineffective against microbes, but some imines showed excellent results. In general, the compounds were more active against...
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Synthesis and evaluation of potential antimicrobial agents based on steroidal scaffold
Požárová, Pavla ; Krátký, Martin (advisor) ; Matouš, Petr (referee)
Antibiotic resistance represents a significant threat to humanity. To combat this trend, the development of new effective substances can be employed to potentially reverse its progression. Due to the broad range of biological activities exhibited by steroid structures, estrone was chosen as the starting material and was modified through various reactions. In total, fifteen new compounds were synthesized, which were tested for their antibacterial, antifungal, and antimycobacterial activities, and additionally for cholinesterases inhibition. The modification of estrone primarily involved two different approaches, resulting in the formation of hydrazones and esters. Twelve compounds were prepared through these steps. For the remaining three derivatives, changes in the starting materials or procedures were necessary. In the case of four compounds, it was necessary to synthesize one of the reactants. The yields ranged from 62% to 95% for hydrazones and from 8% to 54% for esters. The antibacterial activity was tested against four selected Gram-positive and Gram-negative strains. Antifungal activity was evaluated against four yeasts and filamentous fungi. Antimycobacterial activity was tested against five mycobacterial strains. All these methods utilized the microdilution broth method. The tested...
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Synthesis and coordination behaviour of diphenylphosphinoferrocifen
Křelinová, Magda ; Schulz, Jiří (advisor) ; Kubíček, Vojtěch (referee)
Title: Synthesis and coordination behaviour of diphenylphosphinoferrocifen Author: Bc. Magda Křelinová Department: Department of Inorganic Chemistry Supervisor: RNDr. Jiří Schulz, Ph.D. Abstract: Ferrocifen, as a ferrocene analog of a commonly used drug - tamoxifen, showed promising activity against breast cancer cells - both the hormone-dependent type and the hormone-independent one. The treatment of the latter is a struggle for today's medicine and a new effective treatment is urgently needed. One of the goals of this thesis was to optimize the synthesis of 1-{1-[bis(4-hydroxyphenyl)methylene]propyl}-1'-(diphenylphosphino) ferrocene (compound 4), which will provide a way of conjugating the ferrocifenol moiety to metal complexes, that are also studied as anticancer agents. The combination of those effects could provide some interesting results against cancer cells. In this thesis, 8 complexes of compound 4 as a ligand were prepared. All of these compounds were subsequently tested on cancerous (MDA-MB-231, and A549) as well as non-cancerous (MCF10A) cell lines to assess their biological activity and potential selectivity towards cancerous cells. Ru Cl Cl P Ph2 Fe HO OH 6 Ru Cl Cl P Ph2 Fe HO OH 7 Ru Cl Cl P Ph2 Fe HO OH 8 Ru Cl Cl P Ph2 Fe HO OH 9 Ir Cl Cl P Ph2 Fe HO OH 10 Rh Cl Cl P Ph2 Fe HO OH 11 Fe P...
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Synthesis and evaluation of potential drugs for neurodegenerative diseases
Foltýnová, Eva ; Krátký, Martin (advisor) ; Vinšová, Jarmila (referee)
The topic of this thesis is the synthesis of oxadiazole derivatives and their precursors as potential therapeutics for neurodegenerative diseases, and their evaluation primarily as potential inhibitors of cholinesterases (CHE). The theoretical part of this thesis focuses on Alzheimer's disease, particularly its pathophysiology, diagnosis, and treatment. It also discusses CHE inhibitors that are already clinically used, as well as new structures with potential for future clinical use. Additionally, it addresses the oxadiazole fragment, its chemical and biological properties. In the experimental work, derivatives of 1,3,4- and 1,2,4-oxadiazoles were synthesized, which differed not only in the type of oxadiazole but also in their substitution. These substances were prepared by the cyclization of precursors, which were also prepared and tested. For 1,3,4- oxadiazoles, besides their inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), their potential antimycobacterial, antibacterial, and antifungal activities were tested. For 1,2,4-oxadiazoles, so far, only their inhibitory activity against AChE and BuChE has been tested. A total of twenty-two substances were synthesized, and the yields of these syntheses ranged from 21-97%. The compound with the lowest IC50 value...
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Synthesis and evaluation of novel disinfectant agents
Veselý, Jan ; Krátký, Martin (advisor) ; Vinšová, Jarmila (referee)
This diploma thesis deals with the synthesis and use of new quaternary ammonium salts (QACs). These substances have been commonly used for decades as disinfectants, antiseptics, antimicrobial additives, preservatives, and currently their decontamination potential using micellar catalysis is being investigated. The theoretical part contains information about the mechanism of action on individual types of microbes, an overview of physicochemical properties, especially solubility and determination of logP, micelle formation. Furthermore, microbial resistance and the mechanism of cross-resistance between QACs and antibiotics (ATB) are described here. The experimental part mainly deals with the synthesis of new QACs, which we expect to have an antimicrobial effect and the potential of creating a micellar microenvironment for micellar catalysis. The first series of reactions is focused on the preparation of three molecules of monoquaternary ammonium salts from the starting material benzylamine, to which two homologous aliphatic alkyl chains C8, C10 and C12 and a hydroxyethyl group are attached. This structure is a necessary carrier of the antimicrobial effect and the formation of micelles. All three molecules were successfully prepared. The second series of reactions is focused on the preparation of nine...
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Synthesis and evaluation of potential antifungal agents
Straková, Jana ; Krátký, Martin (advisor) ; Novotná, Eva (referee)
Mycotic systemic infection is often very severe, whether due to patient immunodeficiency, the side effects of available antifungal agents, or clinical or drug resistance. Emphasis should therefore be placed on the timely determination of the correct diagnosis, appropriate indications of current drugs, and especially the development of new antifungal agents (ATM). The core of all synthesized compounds is the molecule of itaconic acid (IA) or its anhydride. The starting molecule was chosen based on its broad spectrum of biological activities, including antibacterial and antifungal activities. The aim was to create ten monoamides using a one-step synthesis of IA anhydride with the appropriate chlorinated aniline. These monoamides were then cyclized to form ten imides. The yields of the reactions to form the monoamides were high, with two exceptions (24% and 31%), and were generally above 80%. The yields of the reactions to form the imides were lower, ranging from 29% to 86%. The antimicrobial activity was tested using the broth microdilution method for all imides and most monoamides. All compounds were ineffective against gram-negative bacteria, and very low activity against gram-positive bacteria was shown by the compounds 1-(2,4,6-trichlorophenyl)-3-methylene-2,5-pyrrolidinedione,...
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Advanced electron diffraction methods for structural description of zeolites
Laštovičková, Anna ; Mazur, Michal (advisor) ; Tyrpekl, Václav (referee)
Electron diffraction (ED) is a powerful tool for the structure determination of crystalline materials. It offers an alternative to single crystal X-ray diffraction (SCXRD) that is often limited by the size of synthesized crystals. Electron diffraction allows analysis of materials at the nanoscale, thus it is particularly useful for samples which crystals are too small for other methods. ED utilizes electrons for collection of diffraction patterns that can be performed in a transmission electron microscope (TEM). Collected ED patterns are further analyzed allowing for the determination of unit cell parameters, lattice type, and even the crystal structure itself. Nevertheless, the effective structure determination from standard ED patterns requires in-depth expertise and data collection is time consuming. Current development of ED methods focuses on the facilitation and automatization of data collection and processing. Notably, highly advanced, continuous rotation electron diffraction (cRED) data collection takes only a few minutes enabling structure determination within a single day. In this work, I present the utilization of cRED method for the structural characterization of zeolites. These materials are often synthesized as polycrystalline samples with crystals of nanometer in size. This makes...
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Model-Based Reinforcement Learning for POMDPs
Smíšková, Lucie ; Andriushchenko, Roman (referee) ; Češka, Milan (advisor)
Markovské rozhodovací procesy s částečným pozorováním nám umožňují modelovat systémy obsahující stavovou neurčitost. Jsou užitečné, pokud máme pouze částečné informace o stavech (tak zvaná pozorování). Cílem této práce bylo vyvinout metodu kombinující induktivní syntézu a zpětnovazebné učení k vytvoření co nejlepšího konečně stavového kontroléru. Tato metoda poté byla implementována jako rozšíření nástroje PAYNT.
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Preparation and characterization of optically active nanorods
Gaizura, Filip ; Liška, Petr (referee) ; Dvořák, Petr (advisor)
This work focuses on the qualitative study of the preparation and optical characterization of CsPbBr3 perovskite nanorods. The first part contains a brief description of 3D, 2D and 0D perovskite nanostructures, and then focuses on the description of the 1D structure - perovskite nanorods, their possible crystal structures, stability, possible preparation methods, optical properties and use in various optoelectronic devices. The practical part discusses in detail the preparation of CsPbBr3 perovskite nanorods using colloidal synthesis based on ligand-assisted reprecipitation and chemical division at room temperature. Furthermore, the synthesized nanorods are analyzed for morphology and their absorption and photoluminescence spectra are measured with the aim of verifying the dependence of optical properties on the mentioned morphology.
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