National Repository of Grey Literature 60 records found  1 - 10nextend  jump to record: Search took 0.00 seconds. 
Synthesis of lansoprazole analogs with potential antimycobacterial activity
Kubásková, Mária ; Roh, Jaroslav (advisor) ; Krátký, Martin (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Organic and Bioorganic Chemistry Author: Mária Murínová Supervisor: doc. PharmDr. Jaroslav Roh, Ph.D. Title of diploma thesis: Synthesis of lansoprazole analogs with potential antimycobacterial activity Mycobacterium tuberculosis is a bacterium that causes a serious infectious disease, tuberculosis. Recent studies show an increase in the number of patients suffering from this disease, pointing to the increasing resistance of this bacterium to most antibiotics. Given the current globalization of the world, as another factor contributing to the spread of tuberculosis in areas where the disease has been under control so far, it is essential to focus on the development of new antituberculosis drugs. Recent studies have reported that a promising candidate is lansoprazole, which is known primarily as gastric proton pump inhibitor. The mechanism of the antimycobacterial effect is that lansoprazole, after intracellular reduction to lansoprazole sulfide, kills M. tuberculosis by inhibiting cytochrome bc-1. This makes lansoprazole sulfide an excellent compound for further structural optimization and study of its structure-activity relationships. The aim of this work was to modify the structure of the lansoprazole and to prepare its...
Synthesis and evaluation of potential antimicrobial agents
Sýkorová, Jana ; Krátký, Martin (advisor) ; Matouš, Petr (referee)
Antibiotic resistance is a global problem and the development of new drugs, among other approaches, should contribute to mitigating the consequences. All newly prepared compounds are based on the 4,6-dimethylpyrimidine-2-amine, in some syntheses its derivative sulfamethazine was used as a starting compound. The starting molecule was chosen based on the antimicrobial activity of 4,6-dimethylpyrimidine-2-amine derivatives. The aim of three one-step syntheses was to prepare sulfonamides from 4,6-dimethylpyrimidine-2-amine and corresponding sulfonyl chlorides. Other ten also one-step reactions led to the preparation of Schiff bases, which are mostly based on salicylaldehyde and benzaldehyde derivatives. Different methods were used, yields ranged from 13 % to 48 % for sulfonamides and from 13 % to 96 % for Schiff bases. All thirteen compounds were tested for antibacterial (against selected G+ and G- strains) and antifungal activity using the microdilution broth method. In general, the compounds were ineffective against G- bacteria and, on the other hand, showed the greatest activity (i.e., lowest minimum inhibitory concentrations, MIC) against fungi. Sulfonamides were ineffective. The lowest MICs for both fungi (3.9 µmol l-1) and bacteria (15.62 µmol l-1) were found for...
Novel compounds active against methicillin-resistant staphylococci and vancomycin-resistant enterococci
Pokorná, Anežka ; Krátký, Martin (advisor) ; Konečná, Klára (referee)
The bachelor thesis deals with compounds acting on methicillin-resistant staphylococci and vancomycin-resistant enterococci. It overviews suitable established or newly used antibiotics that are effective in combating these resistant strains, as well as new potentially useful compounds. The theoretical part includes information about particular strains, their characteristics, laboratory diagnostics and an overview of the diseases they cause, as well as information on mechanisms of resistance to clinically used antibiotics. Knowledge of these mechanisms is important for the future synthesis of new drugs. The second part reports the drugs themselves and promising compounds in development that are suitable for particular strains. The thesis discusses both already established compounds and potential compounds in various stages of (pre)clinical development. Keywords Antibiotics, biofilm, methicillin, methicillin-resistant staphylococci, natural derivatives, new compounds, resistance, vancomycin, vancomycin-resistant enterococci
Oxadiazoles as potential drugs III.
Lukáčová, Michaela ; Kučerová, Marta (advisor) ; Krátký, Martin (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Title of diploma thesis: Oxadiazoles as potential drugs III. Student: Michaela Lukáčová Supervisor: PharmDr. Marta Kučerová, Ph.D. Theoretical part of this diploma thesis summarises biological activity of 1,2,4-oxadiazoles, while focusing primarily on their antimycobacterial, antibacterial and antifungal effects. 1,2,4-Oxadiazoles are compounds with versatile biological applications, therefore their antioxidant, antiinflammatory, analgesic and cytostatic activity is also mentioned. Based on the facts in the theoretical part, it is perceptible, that 1,2,4-oxadiazoles are substances with great therapeutical potential not only for the treatment of tuberculosis, but also many other diseases. Thus, the experimental part of this work is focused on the synthesis of 5-substituted 3-pyrazinyl-1,2,4-oxadiazoles followed by evaluation of their antibacterial, antifungal and most importantly antimycobacterial activity. Synthesic procedure for each compound is also included. Nine compounds were successfully synthesized, six of them were prepared by reaction of N'-hydroxypyrazine-2-carboximidamide with different carboxylic acid anhydrides and three of them by reaction of...
Modification of antimycobacterial active sulphonamides
Kufa, Martin ; Krátký, Martin (advisor) ; Vinšová, Jarmila (referee)
The importance of the searching for novel antimycobacterial active agents is continually increasing with growing mycobacterial resistance to currently used drugs. However, the resistance-related problems are also associated with other bacteria and fungi. The systematic modification of compounds with a known antimicrobial activity represents one of the possible approaches to overcome this problem. Sulphonamide derivatives may be considered to be such a kind of compounds. That is why we synthesized various sulphathiazole derivatives. Amides were obtained by the reaction of sulphathiazole with appropriate acyl chlorides, substituted ureas from corresponding isocyanates. These ureas were cyclized via oxalyl chloride to form substituted 2,4,5-trioxoimidazolidines. Among derivatives evaluated for their antimycobacterial action, 4-(3- phenethylureido)-N-(thiazol-2-yl)benzenesulphonamide showed the highest activity. Its minimum inhibitory concentrations (MIC) against Mycobacterium tuberculosis My 331/88 (4 µmol/l) were superior to those obtained for sulphathiazole. In the case of nontuberculous mycobacteria (M. avium My 330/88, M. kansasii My 235/88 and M. kansasii My 6509/96), their activities were comparable (≥ 2 µmol/l). Amides showed also a significant antimycobacterial activity, especially against M....
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-...
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...
Derivative of Aminobenzoic Acids as Potential Antimicrobial Agents
Brokešová, Kateřina ; Krátký, Martin (advisor) ; Janďourek, Ondřej (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Organic and Bioorganic Chemistry Candidate: Mgr. Kateřina Brokešová Consultant: PharmDr. Mgr. Martin Krátký, Ph.D. Title of Thesis: Derivatives of Aminobenzoic Acids as Potential Antimicrobial Agents The increasing resistance to previously unnecessarily used antimicrobial drugs has led to the need for search and synthesis of new drugs including Schiff bases. The rigorous thesis deals with the synthesis and subsequent characterization and evaluation of biological properties of new Schiff bases synthesized from substituted salicylaldehydes and aromatic amino acids and their derivatives (3-aminobenzoic, 3,5-diaminobenzoic acids and esters of 4-aminobenzoic acid). The prepared derivatives were evaluated for their antibacterial, antifungal and antimycobacterial activities; cytotoxicity was also investigated for the most active ones. Most of the Schiff bases exhibit antibacterial activity with minimum inhibitory concentration (MIC) from 7.81 µM, which is comparable with a standard drug bacitracin for some strains. Schiff bases appear to be more effective against Gram-positive bacteria including methicillin- resistant Staphylococcus aureus. The newly synthesized compounds are also effective against yeasts and filamentous fungi. The...

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See also: similar author names
10 Kratký, Michal
2 Krátký, Matouš
10 Krátký, Michal
1 Krátký, Milan
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