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Xanthone-boronic acids: An insight into the synthesis of borylated xanthone derivates
Houngbedji, Priam-Amedeo ; Doležal, Martin (advisor) ; Zitko, Jan (referee)
CHARLES UNIVERSITY FACULTY OF PHARMACY IN HRADEC KRÁLOVÉ DEPARTMENT OF PHARMACEUTICAL CHEMISTRY AND PHARMACEUTICAL ANALYSIS DIPLOMA THESIS XANTHONE-BORONIC ACIDS: AN INSIGHT INTO THE SYNTHESIS OF BORYLATED XANTHONE DERIVATIVES Supervisor: prof. PharmDr. Martin Doležal, Ph.D. HRADEC KRÁLOVÉ 2021 PRIAM-AMEDEO HOUNGBEDJI Abstract - English The development of Bortezomib 5 and discovery of its potential in the treatment of multiple myeloma has sparked hope, and a close attention is paid in medicinal chemistry to the synthesis of boronic acid derivatives as well as the evaluation of their anticancer, antimicrobial, and other activities. Parallelly, xanthones and xanthone derivatives are compounds thoroughly studied for their potential in the treatment of cancer, and their good antimicrobial, anti-inflammatory, antiviral and anticonvulsant activity. It is only natural that efforts are oriented towards the synthesis of xanthone boronic derivatives. 3,6-Dihydroxyxanthone 10 was chosen as a precursor for the development of a procedure to borylate xanthones, mainly due to its easy synthesis and availability. From 10, 3,6-ditrifylxanthone 11 was easily prepared. The synthesis of 3,6- bis(pinacolatoboron)xanthone 8 from 11 was achieved using bis(pinacolatodiboron) B2pin2 as a borylation agent under Pd(dppf)Cl2 catalysis...
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DNS firewall and its deployment and integration in cyber center
Doležal, Martin ; Kubánková, Anna (referee) ; Jeřábek, Jan (advisor)
This bachelor's thesis deals with the deployment, integration, and testing of a DNS firewall in a security operations center. It describes the connection of endpoints and remote local area networks to the DNS firewall located in the security operations center. Furthermore, the enforcement of the DNS firewall is described. The main goal of the thesis was to deploy and integrate a DNS firewall inside a security operations center. The first chapter describes the security operations center in general. The second chapter deals with the DNS system. The following chapter describes the security of the DNS system and security of DNS requests, the reader is informed of the term DNS firewall and RPZ and VPN technologies. The fourth chapter describes the DNS firewall deployment process and its integration in a real security operations center. The next chapter describes connection methods of endpoint and remote local area networks to the DNS firewall and its enforcement inside the security operations center. The last chapter deals with performance testing and deployed DNS firewall availability. The outcome of the thesis involves a deployed, integrated, fully-functional, and tested DNS firewall in a real-world security operations center. The Bind software package along with the RPZ technology was used to implement and deploy the DNS firewall. For testing and connection of endpoints, the VPN technology, and the RIPE Atlas network was used.
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Study of alkali metals ions diffusion in hardened cement
Doležal, Martin ; Janča, Martin (referee) ; Šoukal, František (advisor)
This master thesis is aim to study alkali diffusion (sodium, potassium) in hardened cement paste body. It´s deal with impact of various sorroudings (hydroxide, nitrate and carbonate) in various concentrations and temperature effect. This work is also deal with changes in cement paste and medium. Teoretic part is talking about cement production and cement chemistry, alkali-silica reaction, plasticizer, diffusion an cement testing metods. This work is aimed to white (Aalborg CEM I 52,5 R – SR 5) and road (Mokrá CEM I 42,5 R – sc) cement. Experimental part describes constitution of tested cement pastes, conservation of them and sampling. Diffusion is study by ICP-AES which affected the loss of alkali from the solution and SEM which affected alkali migration (diffusion) in cement paste. In several cases, the formation of a saturated alkali edge was observed, followed by steady diffusion. In the case of potassium there was very slow diffusion through the body mass. The influence of medium and temperature was evaluated as the most significant. The effect of medium concentration wasn´t significant. Also changes in the porosity on the body were observed. The diffusion itself was affected by secondary products gorwing on the surface of body and in the medium. The work deals with them in the last part.
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Pyrazine derivatives as potential drugs III
Hošťálková, Anna ; Doležal, Martin (advisor) ; Kopecký, Kamil (referee)
Deriváty pyrazinu jako potanciální léčiva III. Tuberkulóza je problém v celosvětovém měřítku. Rostoucí počet nakažených lidí, vznik lékově rezistentních kmenů Mycobacterium tuberculosis a ko-infekce HIV vedly k naléhavé potřebě nových antituberkulotik. Tato diplomová práce referuje o současných léčivech používaných při léčbě tuberkulózy a některých nových potenciálních antituberkuloticích. Také bylo v rámci diplomové práce syntetizováno deset nových látek, derivátů anilidů kyseliny pyrazin-2-karboxylové, které byly charakterizovány jejich fyzikálními vlastnostmi a poté byla zkoušena jejich antimykobakteriální a antifungální aktivita in vitro. Abstract Pyrazine derivatives as potential drugs III. Tuberculosis is a health problem worldwide. The increasing number of infected people, emergence of drug resistant strains Mycobacterium tuberculosis and HIV co-infection have resulted in the urgent need for new antituberculosis drugs. This degree work reviews drugs used in current treatment for tuberculosis and some of new potential anti-tuberculosis drug candidates. Within the task of this work were also synthesized ten new compounds, derivatives of anilides of pyrazin-2-carboxylic acid, which were characterized by physical properties and then was assayed their antimycobacterial and antifungal activity in...
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Pyrazine Derivates as Potential Antituberculotic Drugs
Kačírek, Michal ; Doležal, Martin (advisor) ; Kopecký, Kamil (referee)
Title of rigorous thesis: Pyrazine derivates as potential antituberculotic drugs Author: Mgr. Michal Kačírek In this rigorous thesis the recherche was realized which was focused on recent incidence of tuberculosis in the world, the possibility o f present therapy and the new trends in therapy as well. This thesis dealt with synthesis of undocumented compounds in literature. The starting compound was 5-chloro-6-methylpyrazine-2,3- dicabronitrile. The compounds were developed by aminodehalogenational reaction, linked to alkyl descriptor across amino group, whereas side chains were anal ogously extended. It can be said that the product was developed by reaction of 5 -chloro-6- methylpyrazine-2,3-dicabronitrile with corresponding primary aliphatic amine. Final compounds were characterized by thaw point, TLC, elementary analysis, 1 H a 13 C NMR and IR. All compounds were liable in vitro testing on their biological activity - antimycobacterial, antifungal and antibacterial. In the group of antituberculosis test ing the activity grew up from the least to the most lipophility compound.
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Intracellular trafficking of an anti - Amyloid Protein Precursor antibody.
Zitko, Jan ; Doležal, Martin (advisor) ; Trejtnar, František (referee)
Intracellular trafficking of an anti-Amyloid Protein Precursor antibody Alzheimer's disease is characterized by over-accumulation of beta-amyloid peptide (Aβ) in the brain. Aβ is produced by proteolytic cleavage of beta-amyloid precursor protein (APP) by β- and γ-secretases. Novel monoclonal antibody, 2B12, has been shown to bind to β-secretase cleavage site of APP, reducing the production of APP, presumably by preventing the cleavage by steric hindrance. 2B12 is hypothesized to bind to APP molecules exposed on the cell surface and to be internalized in the form of complex with APP via natural endocytic pathway. This hypothesis was confirmed by San Pei Ho's (2007), who followed the internalization of 2B12 in living astrocytoma MOG-G-UVW, cells in time-course experiment. This project is focused on intracellular trafficking of 2B12 and its localization within specific cellular compartments. Experiments were performed with fixed astrocytoma MOG- G-UVW cells (constitutively expressing APP). Originally planned experiments with live cells could not be performed due to decreased stability of 2B12 (causes remain unknown). 2B12 was tested for colocalization with polyclonal affinity purified antibodies labelling subcellular markers (proteins) associated with compartments known to participate in APP...
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