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Synthesis of salicylanilide esters active against MDR-TB
Vosátka, Rudolf ; Vinšová, Jarmila (advisor) ; Krátký, Martin (referee)
VOSÁTKA, Rudolf., Synthesis of salicylanilide esters active against MDR-TB, Hradec Králové: Faculty of Pharmacy of Charles University, 2013, 54 s, Diploma thesis. This diploma thesis deals with the synthesis and activity of salicylanilides and their esters against MDR-TB. Specifically, 4-bromo-3-(trifluoromethyl) aniline, 3,5-bis (trifluoromethyl) aniline and their esters as isonicotinates, pyrazincarboxylates and 1H- imidazole-4-carboxylates. Moreover, there is also 5-chloro-N-(3,4-dichlorophenyl)-2- hydroxybenzamide, which inter alia demonstrates the best MIC compared to other synthesized substances. Thesis summarizes problems of tuberculosis, its current treatment and supplementing to the current trend in the development and research on specific examples of potential drugs. Much of this thesis deals with salicylanilides.
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Synthesis of novel isoniazid derivatives
Rychtarčíková, Zuzana ; Vinšová, Jarmila (advisor) ; Krátký, Martin (referee)
TB remains a major cause of population mortality in the world. Research of new substances with antimycobacterial activity is emphasized also because of increasing occurrence of resistance in case of monotherapy as well as combination therapy with AT of first and second line. Current trends in the development rest in the connection of two molecules into one - the so-called double active compound - by means of various linkers. In the process of synthesis of 2-isonicotinoyl-N-substituted phenylhydra- zinecarboxamides, a carbonyl bridge was used. The synthesis of these substances was realized by two methods. In the first one, the reaction was based on substituted isocyanate; in the second one, preparation of isocyanate in situ from a substituted aniline using triphosgene was applied. All substances were tested for in vitro antimycobacterial activity. The substance 2-isonicotinoyl-N-(2,4,6-trichlorophenyl)hy- drazinecarboxamide exhibited the highest activity against Mycobacterium tuberculosis 331/88 with MIC value (4 μmol/L). The compounds were also tested for other strains of mycobacteria - Mycobacterium avium 330/88, Mycobacterium kansasii 235/80 and Mycobacterium kansasii 6509/96. Synthesis of N-substituted phenyl-5-(pyridine-4-yl)- 1,3,4-oxa-diazol-2-amines was based on the selected and prepared...
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The use of laser microdissection for the genotyping of biological material isolated during an abortion.
Beranová, Karina ; Krátký, Martin (advisor) ; Kopečný, Michal (referee)
The use of laser microdissection for the genotyping of biological material isolated during an abortion Abstract In forensic genetics laser microdissection is used mainly as a method of cell separation from samples of mixed biological traits of sexually motivated crimes. It can also be used in paternity testing via genotyping of biological material isolated during an abortion. The foetal part of placenta is separated from the acquired samples and a pure DNA profile of the foetus is determited. This DNA can be compared to the suspect's DNA. The goal of this project is the application of laser microdissection to separate chorionic villi from a placenta and the subsequent genetic analysis leading to the determination of a pure foetal DNA profile. A secondary goal was the preparation and optimization of the method necessary for its introduction to forensic practice. In the first phase the optimization of the sample preparation was conducted on test sections of muscular tissue and epithelial cells from a buccal swap. Experimental material acquired during abortions of voluntary donors was used in the second phase. This technique was simultaneously tested on material directly linked to criminal acts. The separation of 10 chorionic villi cells with the method of laser microdissection eventually resulted in the...
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Design and Synthesis of New Compounds Active Especially Against Multidrug-Resistant Mycobacterial Strains
Krátký, Martin ; Vinšová, Jarmila (advisor) ; Doležal, Martin (referee) ; Rádl, Stanislav (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Inorganic and Organic Chemistry Candidate Martin Krátký Supervisor Prof. Dr. Jarmila Vinšová, Ph.D. Title of Doctoral Thesis Design and Synthesis of New Compounds Active Especially against Multidrug-Resistant Mycobacterial Strains This work is focused mainly on the field of searching of new potential antimicrobial agents, particularly against multidrug-resistant Mycobacterium tuberculosis strains, based on the modification of the salicylanilide (2-hydroxy-(N-phenyl)benzamide) group. The second research topic is a study of the rearrangement in the series of salicylanilide amino acids esters to form 2-hydroxy-N-[2-oxo-2-(phenylamino)-alkan-2-yl]benzamides called "diamides". At the beginning, the thesis summarizes some basic facts about tuberculosis, a very important and serious bacterial infectious disease caused by Mycobacterium tuberculosis complex, about its treatment and related troubles and limitations. Proper attention is given for the problematic of drug-resistant tuberculosis, especially multidrug-resistant and extensively drug-resistant forms, their epidemiology and therapy. The development of new drugs against multidrug-resistant tuberculosis is largely discussed, including requirements for them, recent...
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Synthesis of salicylanilide prodrugs
Krátký, Martin ; Vinšová, Jarmila (advisor) ; Imramovský, Aleš (referee)
KRÁTKÝ, Martin. Synthesis of Salicylanilide Prodrugs. Hradec Králové: Faculty of Pharmacy of Charles University, 2008. 75 pp. Diploma Thesis. This diploma thesis is concerned with synthesis of antibacterial prodrugs based on esters of salicylanilides with amino acids. First there are characterized prodrugs and their importance and then biological activities and application of salicylanilides. The main goal of this work was the synthesis of prodrugs of salicylanilides amino acids esters. Some synthesized compounds were evaluated especially for their activity against atypical Mycobacteria strains. These compounds possess antimycobacterial activity, but it is lower than initial salicylanilide 5-chloro- N-(3-chlorophenyl)-2-hydroxybenzamide. This diploma thesis acknowledges rearrangement after N-deprotection and α-amino group liberation of N-protected amino acids esters with salicylanilides to furnish diamides. The diamide was esterified by Z-amino acids (L-phenylalanine and glycine). These obtained esters were N- deprotected and the amino group was liberated. After this liberation there was described rearrangement to furnish probably triamides, analogously to furnishing of diamides. There are discussed two possible mechanisms of rearrangement - with forming of seven-membered benzoxazepinedione rings...
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Laser microdissection in forensic genetics: genetic analysis of sexual abuse evidence
Faltýsková, Zuzana ; Kopečný, Michal (referee) ; Krátký, Martin (advisor)
Laser microdissection is a novel technique of cell separation under microscopic view utilizing a laser beam. It has been used for cell separation from mixed samples in forensic genetics, such as vaginal smear in cases of sexual assault. In a rape investigation, few cells are usually recovered as the only evidence available for the assailant identification. When analysing a resistant cell type such as sperms, an effective and reliable method is required. This study aims to optimise the genetic analysis of laser microdissected sperms and to take the optimal protocol into practice. The goal is to develop a technique capable of recovery of reliable genotyping results from just a few cells. Genetic analysis was optimised for sperms separated from pure semen samples by laser microdissection. After optimisation, it was validated for sperms recovered from a vaginal smear. In the resulting genetic profiles some artifacts occured, that have been reported in samples with low DNA content. Possible solutions of these artifacts occurrence and elimination are discussed. In conclusion, the developement of an efficient and reliable genetic analysis method was successful: 10 sperms were recovered from vaginal smear and the genotyping result was capable of individual identification of the sperm donor. Powered by TCPDF...
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Influence of benzoxazinedione derivatives on selected mycobacterial enzymes
Švidrnochová, Michaela ; Novotná, Eva (advisor) ; Krátký, Martin (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Mgr. Michaela Švidrnochová Supervisor: RNDr. Eva Novotná, Ph.D. Title of Thesis: Influence of benzoxazinedione derivatives on selected mycobacterial enzymes Tuberculosis is an insidious infectious disease with more and more increasing incidence in certain regions. It is difficult to treat by the available means because of increasing cases of multidrug resistance, which is defined as a resistance of M. tuberculosis at least to two primary antituberculotic drugs - rifampicin and isoniazid. That's why is necessary to search for new substances which interfere with the metabolic pathways of Mycobakterium tuberculosis. Enzyme inhibitions in different levels of these pathways are considered to be a target of the new potencial antituberculotic drugs. In this work, influence of monosulphur and disulphur derivatives of 3-(4-alkylphenyl)-2H- 1,3-benzoxazine-2,4(3H)-dione on enoyl-ACP-reductase, dihydrofolate reductase, isocitrate lyase and FtsZ was tested by thermal shift assay, spectrofotometric method and light scattering. The results showed that the dihydrofolate reductase is not a drug target of selected inhibitors. Isocitrate lyase was the most inhibited by sulphur derivative 3-(4-terc-...
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PLC simulation using TwinCat tool
Krátký, Martin ; Uher, Václav (referee) ; Mašek, Jan (advisor)
Bachelor project is about options in TwinCat 2 for programming the programmable logic controller (PLC). As part of the work will be described the principle of the PLC and PLC uses nowadays. The principe of developing tool TwinCAT will be described and an overview of the programming languages that standard IEC / EN 61131-3. The main contribution of this work is to create a program description in TwinCAT development tool in version 2. The main result will be a simulation of robotic arm created in TwinCAT version 3 and for this simulation will also be created graphical interface in Visual Studio in language C#.
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Analysis of technical-economic parameters of the tractor kits in transport
Krátký, Martin ; Slimařík, Dušan (referee) ; Bauer, František (advisor)
This thesis deals with the use of the tractor in agricultural transport. The first part describes the current status in construction of tractor engines, transmissions and chassis that are used in tractors suitable for transport. The theoretical section includes an overview of the legislative requirements that must be followed for the tractor kits in transport on the road. The main objective of this thesis was to evaluate a measuring of fuel consumption and efficiency of the tractor JCB Fastrac 185-65 with two flatbed trailers. For this purpose was created the methodics off terrain measurement, which were carried out for different operation modes of the engine. The results were tabular and graphical processing including determining the accuracy of the method by calculating the relative error of measurement. For comparison a theoretical calculation of the consumed fuel was made. The aim of the measurements was to demonstrate fuel-saving during operation engine in the economic field and get an overview about fuel consumption and efficiency kits.
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