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Methodical Approach to Evaluate the Efficiency of Road Infrastructure Construction using the PPP Projects
Doležal, Martin ; Póč, David (referee) ; Režňáková, Mária (advisor)
This diploma thesis analyses and elaborates a methodical tool for evaluating the advantage of realization of construction of road infrastructure in the form of a PPP project. Furthermore this tool is subsequent applied to a particular project. The introductory part summarizes the basic theoretical knowledge regarding the project financing in the form of public-private partnerships. In the following part, a methodological tool for comparing the value for money based on different methods of realization. In the last part of the diploma thesis, this methodical tool is applied to a specific project, including a basic feasibility study.
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Preparation of Pyrazinamide Derivatives as Potential Antituberculotics (Study of Structure Activity Relationships)
Semelková, Lucia ; Doležal, Martin (advisor) ; Malík, Ivan (referee) ; Nencka, Radim (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department: Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Candidate: Mgr. Lucia Semelková Supervisor: Prof. PharmDr. Martin Doležal, Ph.D. Consultant: PharmDr. Jan Zitko, Ph.D. Title of Doctoral Thesis: Preparation of Pyrazinamide Derivatives as Potential Antituberculotics (Study of Structure Activity Relationships) This doctoral thesis is focused on search for novel pyrazinamide derivatives with potential antitubercular activity. The theoretical part summarizes issues connected with tuberculosis and its epidemiological situation along with factors (resistance and HIV co- infection) that complicate treatment of tuberculosis. A brief overview of antitubercular drugs used in current therapeutic regimens of tuberculosis is outlined. A single chapter is dedicated to pyrazinamide, which belongs to the first-line antitubercular drugs, and its possible mechanisms of action. The last part is focused on potential enzymatic targets of pyrazinamide derivatives. The practical part describes synthesis and biological evaluation of 112 pyrazinamide derivatives with modifications in amide moiety and position 3 on the pyrazine ring. First two series were derived from N-substituted 3-chloropyrazine-2-carboxamides, the third series...
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Design and Synthesis of Hybrid Compounds Based on Tacrin/Resveratrol Derivatives
Jeřábek, Jakub ; Doležal, Martin (advisor) ; Miletín, Miroslav (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Drug Control Student: Jakub Jeřábek Supervisors: Prof. PharmDr. Martin Doležal, Ph.D. Prof. Maria Laura Bolognesi Title of Thesis: Design and Synthesis of Hybrid Compounds Based on Tacrine/Resveratrol Derivatives Alzheimer's disease (AD) is a progressive neurodegenerative brain disorder, in which a progressive dementia appears. The cause of AD is currently unknown, however, scientific research has revealed several pathological hallmarks - β-amyloid plaques and neurofibrillary tangles. These changes cause gradual disintegration of nerve cells and they change the metabolism in the brain. The current drugs are not able to treat the cause of the disease, being able only to delay the onset of severe symptoms. The basic drugs for AD treatment are acetylcholinesterase (AChE, E.C. 3.1.1.7) inhibitors and, more recently approved, N-methyl- D-aspartate (NMDA) receptor antagonist memantine. These drugs are able to increase cholinergic activity or preventing glutamate excitotoxicity in the patient's brain, thus improving cognitive functions and delaying severe stages of the disease. One of the emerging approaches in drug synthesis represents multi-target-directed ligands (MTDLs). Apart from the ability...
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Preparation of Pyrazinamide Derivatives as Potential Antituberculotics (Study of Structure Activity Relationships)
Semelková, Lucia ; Doležal, Martin (advisor) ; Malík, Ivan (referee) ; Nencka, Radim (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department: Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Candidate: Mgr. Lucia Semelková Supervisor: Prof. PharmDr. Martin Doležal, Ph.D. Consultant: PharmDr. Jan Zitko, Ph.D. Title of Doctoral Thesis: Preparation of Pyrazinamide Derivatives as Potential Antituberculotics (Study of Structure Activity Relationships) This doctoral thesis is focused on search for novel pyrazinamide derivatives with potential antitubercular activity. The theoretical part summarizes issues connected with tuberculosis and its epidemiological situation along with factors (resistance and HIV co- infection) that complicate treatment of tuberculosis. A brief overview of antitubercular drugs used in current therapeutic regimens of tuberculosis is outlined. A single chapter is dedicated to pyrazinamide, which belongs to the first-line antitubercular drugs, and its possible mechanisms of action. The last part is focused on potential enzymatic targets of pyrazinamide derivatives. The practical part describes synthesis and biological evaluation of 112 pyrazinamide derivatives with modifications in amide moiety and position 3 on the pyrazine ring. First two series were derived from N-substituted 3-chloropyrazine-2-carboxamides, the third series...
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Synthesis and study of photophysical and photochemical properties of phthalocyanines and azaphthalocyanines
Váchová, Lenka ; Zimčík, Petr (advisor) ; Doležal, Martin (referee) ; Imramovský, Aleš (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Candidate: Mgr. Lenka Váchová Supervisor: doc. PharmDr. Petr Zimčík, Ph.D. Title of the doctoral thesis:Synthesis and study of photophysical and photochemical properties of phthalocyanines and azaphthalocyanines Phthalocyanines (Pc) and their aza-analogs azaphthalocyanines (AzaPc) are planar macrocyclic complexes derived from porphyrins with a significant absorption band in the range 620-800 nm. Due to their unique photophysical and photochemical properties, together with the high variability of macrocycle substitution, they are important representatives in the modern concepts of materials, industry, electrotechnics and medicine. They are used as photosensitizers in photodynamic therapy of cancerous and non-malignant diseases, fluorescence quenchers for molecular probe labeling in biology or drug and gene delivery agents in cellular environment. The effect of Pc and AzaPc is influenced by their structure, mainly by the character of peripheral substituents, the central chelated metal and the type of the macrocycle. In the first part of the thesis, the influence of intramolecular charge transfer (ICT) on the series of unsymmetrical tetrapyrazinoporphyrazines and...
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Synthesis and evaluation of novel compounds based on quaternary ammonium salts
Nechanická, Aneta ; Doležal, Martin (advisor) ; Zitko, Jan (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Drug Control Student: Aneta Nechanická Supervisor specialist: PharmDr. Jan Marek, Ph.D. Supervisor: prof. PharmDr. Martin Doležal, Ph.D. Title of Thesis: Synthesis and evaluation of novel compounds based on quaternary ammonium salts Five homologous series of quaternary ammonium salts were prepared by nucleophile reactions. As a starting material were used 1-(2-hydroxyethyl)pyrrolidine, 1- (2- hydroxyethyl)piperidine and 1-(2-hydroxyethyl)imidazole which reacted with C10-C18 bromalkyl reagents, in monoquaternary salts, and C8-C12 dibromalkyl reagents, in bisquaternary salts, with only even number of carbons. Products were verified by nuclear magnetic resonance (NMR) and high resolution mass spectrometry (HRMS). Critical micellar concentration (CMC) were measured by conductometry. Correlation between prolonging alkyl chain and CMC was confirmed.
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Development of a reliable test system for purinergic P2X3 receptors
Tomanová, Šárka ; Doležal, Martin (advisor) ; Pourová, Jana (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Drug Control Student: Šárka Tomanová Supervisors: Prof. PharmDr. Martin Doležal, Ph.D., Prof. Dr. Christa Elisabeth Müller Title of diploma thesis: Development of a reliable test system for purinergic P2X3 receptors Purinergic P2X3 receptor is a ligand-gated ionotropic channel that occurs in all mammalian tissues. The highest occurrence has been observed in central and peripheral nervous system and smooth muscles, where P2X3 receptors participate in pathological disorders such as visceral and neurophatic pain, inflammatory reactions and psychiatric disorders. Compounds capable of blocking P2X3 receptor activity could be therefore used as potential drugs for treatment of these states. P2X3 receptor belongs to fast- desensitizing ionotropic channels, which makes the measurement of its activity very difficult. It was described that one point S15V mutation, in which the amino acid serine in a position 15 is replaced by amino acid valine, slows down the desensitization rate and the signal becomes easily measurable. This simple mutation may be used as an effective tool for characterization of insufficiently explored P2X3 receptor. The P2X3 S15V receptor DNA was inserted into retrovirus and,...
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Derivatives of pyrazine as potential antituberculars (preparation and study of biological properties)
Janďourek, Ondřej ; Doležal, Martin (advisor) ; Farsa, Oldřich (referee) ; Musílek, Kamil (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical chemistry and Pharmaceutical analysis Candidate Mgr. Ondřej Janďourek Supervisor Prof. PharmDr. Martin Doležal, Ph.D. Consultant PharmDr. Jan Zitko, Ph.D. Title of Doctoral Thesis Derivatives of pyrazine as potential antituberculars (preparation and study of biological properties) This work is focused on pyrazine derivatives with the structural relationship to pyrazinamide (PZA) and with the potential antitubercular effect. In the introduction, there are summarized theoretical findings about tuberculosis (TBC), its epidemiology and primarily the development of resistance to current pharmacotherapy. Brief overview of known antituberculars, novel compounds and auspicious molecules in clinical trials is outlined. PZA, which is counted among the first line antitubercular agents, is widely described due to its cardinal role in this thesis. PZA possible mechanisms of action are described together with its pharmacological profile. Finally, brief summary of already prepared derivatives of PZA is stated. Practical part of this thesis is focused on synthesis of three starting compounds (5-chloro-6-methylpyrazine-2,3-dicarbonitrile; 3-chloropyrazine-2-carboxamide; N-benzyl-3-chloropyrazine-2-carboxamide) that were...
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Derivatives of pyrazinecarboxylic acid as potential antituberculotics (synthesis and biological evaluation)
Vaňásková, Barbora ; Doležal, Martin (advisor) ; Zimčík, Petr (referee) ; Malík, Ivan (referee)
Charles University in Prague, Faculty of Pharmacy v Hradci Králové Department: Department of Pharmaceutical Chemistry and Drug Control Candidate: Mgr. Barbora Vaňásková Supervisor: Prof. PharmDr. Martin Doležal, Ph.D. Title of Doctoral Thesis: Derivatives of pyrazinecarboxylic acid as potential antituberculotics (synthesis and biological evaluation) This doctoral thesis deals with searching for potential antituberculotic drugs derived from pyrazinecarboxylic acid. Thesis contains theoretical part, in which problematics of tuberculosis, factors hindering the effectiveness of treatment (development of resistance and HIV coinfection) and current therapeutic practice are outlined. An individual chapter is devoted to the composition of the mycobacterial cell wall. A brief overview of first-line and second-line antituberculars as well as drugs newly introduced into the clinical practice and promising derivatives in various phases of preclinical and clinical trials is further stated. Special attention is dedicated to pyrazinamide, current theories dealing with mechanism of action of this first-line antituberculotic drug and to ribosomal protein S1, a specific target of pyrazinecarboxylic acid. A summary of pyrazinamide derivatives with antimycobacterial activity published since 2011 is listed for...
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Synthesis and in vitro testing of tacrine-troloxic derivatives as potential inhibitors of acetylcholinesterase
Ondřejíček, Aleš ; Doležal, Martin (advisor) ; Zitko, Jan (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Drug Control Student: Aleš Ondřejíček Supervisor: prof. PharmDr. Martin Doležal, Ph.D. Supervisor specialist: PharmDr. Jan Korábečný, Ph.D. Title of Diploma thesis: Synthesis and in vitro testing of tacrine-trolox derivatives as potential inhibitors of acetylcholinesterase Alzheimer's disease (AD) is a complex neurodegenerative disorder, which involves gradual loss of episodic memory and impairment of cognitive functions. Characteristic histopathological hallmarks of AD are neuritic plaques and neurofibrillary tangles present in brain tissue as well as deterioration of cholinergic neurotransmission. Currently there are only two classes of drugs used for the treatment of AD. The first group represents inhibitors of acetylcholinesterase (AChEI), whereas the second only memantin, NMDA receptor antagonist. The aim of the thesis was to synthesize three series of tacrine - trolox derivatives. In particular derivatives of trolox with tacrine, 7-methoxytacrine and 6- chlorotacrine, which were connected by various linkers. To determine the therapeutical potential of new compounds Ellman method was used and results were compared with tacrine, 7-methoxytacrine and 6-chlorotacrine as standards. The...
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