National Repository of Grey Literature 74 records found  previous11 - 20nextend  jump to record: Search took 0.01 seconds. 
Synthesis and evaluation of potential antitubercular drugs based on isoniazid
Kučerová, Kateřina ; Krátký, Martin (advisor) ; Vinšová, Jarmila (referee)
Isoniazid is a first-line drug used against tuberculosis. It is a bactericidal drug with a selectivity for Mycobacterium tuberculosis (Mtb.). The mechanism of action is primarily based on the blockade of mycolic acid synthesis and thus cell wall synthesis. The development of resistance is limiting the therapeutic potential of isoniazid and that is the reason for the development of its new structural modifications. This diploma thesis is focused on synthesis and evaluation of novel isoniazid analogues based on a hydrazone obtained from isoniazid and glyoxalic acid. The free carboxyl group was further modified by various amines to form amides. A total of sixteen substituted 2-(2- isonicotinoylhydrazono)-N-phenylacetamides were prepared and tested for their in vitro antimycobacterial activity on selected strains of mycobacteria - Mtb., M. avium and M. kansasii. The best activity against Mtb. was shown by (E)-2-(2- isonicotinoylhydrazineylidene)-N-(4-propylphenyl)acetamide and (E)-N-(4-butylphenyl)-2-(2- isonicotinoylhydrazineylidene)acetamide, their minimal inhibitory concentration (MIC) is 0.125 µM compared to isoniazid's MIC of 0.5 µM. They were also active against nontuberculous mycobacterium M. kansasii (MIC from 2 µM). Their activity against multidrug- resistant strains was lower due to...
Synthesis and evaluation of antimycobacterial 1,3,4-oxadiazole derivatives
Šikorová, Enikő ; Krátký, Martin (advisor) ; Vinšová, Jarmila (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Organic and Bioorganic Chemistry Author: Enikő Šikorová Supervisor: doc. PharmDr. Mgr. Martin Krátký, Ph.D. Consultant: Mgr. Václav Pflégr Title of diploma thesis: Synthesis and evaluation of antimycobacterial 1,3,4-oxadiazole derivatives Tuberculosis (TB) is a serious infectious disease caused by obligately pathogenic rods of Mycobacterium tuberculosis complex (Mtb.), and it is still among the ten most common causes of death worldwide. One of the main complications of TB therapy is the ever-increasing resistance of mycobacterial strains to conventional drugs. Therefore, the development of new antimycobacterial compounds is crucial to overcome this issue. Research and development of new potential antimycobacterial agents often involve structure modifications of clinically used drugs - frequently the first-line drug, isoniazid (INH). The starting point of this work is also the structure of the already mentioned INH. First, a series of 2-alkyl-5-(pyridine-4-yl)-1,3,4-oxadiazoles and N'-acylisonicotinohydrazides as their synthetic precursors were prepared and evaluated with very promising activity (expressed as minimal inhibitory concentration - MIC) against several mycobacterial strains (MIC Mtb. H37Rv of 1-8 µM). Furthermore,...
Structure-antimycobacterial activity relationships in the series of dinitrophenyl-substituted heterocycles
Mašek, Zdeněk ; Roh, Jaroslav (advisor) ; Krátký, Martin (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Organic and Bioorganic Chemistry Author: Zdeněk Mašek Supervisor: doc. PharmDr. Jaroslav Roh, Ph.D. Title of diploma thesis: Structure-antimycobacterial activity relationships in the series of dinitrophenyl-substituted heterocycles Tuberculosis is an infectious disease with an increasing number of cases each year. Resistance of the pathogen, namely Mycobacterium tuberculosis, to the treatment, even against combined therapy keeps increasing. In 2020, tuberculosis was the second most common cause of death by infectious disease after COVID-19 (it claimed 1.5 million lives) and it is also estimated that with COVID-19 weakening the population, these numbers will only grow. The aim of this work was to develop derivatives of previously studied 1H-tetrazoles and 1,3,4-oxadiazoles, with a sterically hindered sulfur atom (Fig. I), which may protect them from metabolic oxidation and therefore possibly increase their activity against resistant strains of M. tuberculosis as well as other mycobacterial strains and to increase biological halftime of these potential antituberculosis drugs. We prepared two test series, namely 1H-tetrazole series and 1,3,4-oxadiazole series both containing 4 compounds, whose antimycobacterial activities were...
Synthesis and evaluation of potential antimycobacterial agents based on hydrazine derivatives
Koklarová, Apolena ; Krátký, Martin (advisor) ; Vinšová, Jarmila (referee)
Based on research in past years, we have synthetized two similar series of compounds with potential antimycobacterial activity. First series based on isoniazid are (E)-4-[(2- isonicotinoylhydrazineylidene)methyl]-N-phenylbenzamides with great activity (MIC for Mtb. of 0.03-0.125 μM) with few derivatives with moderate activity on nontuberculous mycobacterium M. kansasii (MIC of 2-4 μM). In second series pyridin-4-yl moiety has been exchanged for 3,5-dinitrophenyl, which has shown to be highly effective antimycobacterial scaffold in recent years, therefore derivatives of (E)-4-{[2-(3,5- dinitrobenzoyl)hydrazineylidene]methyl}-N-phenylbenzamide have been prepared. These molecules have shown moderate activity against drug-susceptible Mtb. (MIC of 2-32 μM), and only 4-chloro derivative has surprisingly high activity against non-tuberculous M. avium (MIC of 16-32 μM). Four molecules from the second series even exhibit some activity against MDR- TB and XDR-TB strains.
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....

National Repository of Grey Literature : 74 records found   previous11 - 20nextend  jump to record:
See also: similar author names
10 Kratký, Michal
1 Krátký, Marek
2 Krátký, Matouš
10 Krátký, Michal
1 Krátký, Milan
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