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Synthesis and in vitro evaluation of novel iron chelators based on salicylaldehyde isonicotinoyl hydrazone
Kubeš, Jan ; Roh, Jaroslav (advisor) ; Krátký, Martin (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Organic and Bioorganic Chemistry Author: Jan Kubeš Supervisors: doc. PharmDr. Jaroslav Roh, PhD. PharmDr. Hana Jansová, PhD. Title of Diploma Thesis: Synthesis and in vitro evaluation of novel iron chelators based on salicylaldehyde isonicotinoyl hydrazone Iron ions (Fe) are required in many vital processes. However, this transition metal may also catalyze reactions which results in the formation of toxic reactive oxygen species (ROS), e.g. Haber- Weiss reaction producing highly toxic hydroxyl radicals. Salicylaldehyde isonicotinoyl hydrazone (SIH) is a tridental chelator selectively forming complexes with Fe ions. As a result of its low molecular weight and good lipophilicity, SIH can be administered orally. It readily enters the cells, effectively chelates the intracellular Fe ions, and is therefore able to very efficiently inhibit the Fe dependent processes, such as production of ROS, but also the synthesis of some proteins and enzymes and the processes they regulate (e.g., cellular growth and proliferation). In this work we focused on the design, synthesis and in vitro evaluation of novel SIH analogues, in particular the thio analogue of SIH (thioSIH, A), analogues derived from (di)hydroxybenzophenone (B) and...
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Synthesis of substituted arylguanidines as potential drugs XIII.
Straka, Ondřej ; Palát, Karel (advisor) ; Krátký, Martin (referee)
Charles university Faculty of Pharmacy in Hradec Králové Department of Organic and Bioorganic Chemistry Author: Ondřej Straka Supervisor: PharmDr. Karel Palát, CSc Title of diploma thesis: Synthesis of substituted arylguanidines as potential drugs XIII. The ever increasing number of bacterial strains resistant to the currently used antibiotics intensifies the demand for new structures with antibacterial activity. Similarly, the high mortality of immunocompromised individuals caused by pathogenic fungi requires the synthesis of new drugs with antifungal activity. At the Department of Organic and Bioorganic Chemistry, the Faculty of Pharmacy, Charles University has been studying for many years with the potential antifungal and antibacterial activity of arylguanidins, which has been linked to this work. Two series of derivatives of arylguanidines, totaling seven substances in four-step synthesis were synthesized in the thesis. In the first step, a sulfide was formed by the reaction of substituted chloronitrobenzene and thiol. The nitro group was reduced to the amino group in the next step. The aniline formed was converted to anilinium chloride using gaseous hydrogen chloride. At the last step of the synthesis, anilinium chloride reacted with cyanamide to form arylguanidine. Antifungal and...
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Design of the Tractor's front axle drive
Podhora, David ; Krátký, Martin (referee) ; Prokop, Aleš (advisor)
This master’s thesis is deal with the design of the tractor’s front axle drive to enlarge its braking efficiency of the standing tractor fixed by the parking brake. In the first two chapters, the basic information related to the above stated issue is being summarized. Next, procedure of creating the design including the fundamental calculation proposal is being described. In the last chapter, the strain-stress analysis of the selected partial sections of the design is being presented. The final design is supported with the drawing documentation that is being part of this master’s thesis, too.
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Calculations of parameters of biologically active compounds by the quantum mechanical methods.
Horáček, Ondřej ; Palát, Karel (advisor) ; Krátký, Martin (referee)
8 ABSTRACT The aim of this work is to calculate the parameters of substituted bases and chosen phenylguanidinium cations, earlier synthesized at the Department of inorganic and organic chemistry on the Faculty of Pharmacy CU in Hradec Králové, using quantum chemical methods. I solved chosen problem by using computer programs Gaussian 03W and Hyperchem 8.0.10. I used program Gaussian to optimize the molecules and calculate the energy of the HOMO and LUMO, total energy and the atomic partial charge using the Mulliken population analysis. I used programe HyperChem to calculate the Van der Waals molecular volume; Van der Waals molecular surface; logP; the molar refraction; solvent-accessible surface of the probe size 1.0 Å; 1.2 Å; 1.4 Å; 1.6 Å and the atomic partial charge using methods PEOE. All parameters of selected substituted phenylguanidines above have been successfully calculated, and listed in the tables in the chapter called results. The calculated results were discussed in chapter called discussion. The calculated parameters will be used for further correlations and QSAR studies that will help to understand the biological activity of substituted phenylguanidines and hence their effect on the human organism.
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Synthesis of antimicrobial compounds based on derivatives of salicylic acid
Tvrdý, Václav ; Krátký, Martin (advisor) ; Vinšová, Jarmila (referee)
Schiff bases are widely used both in technical practice and in the field of medicine. For their antimicrobial activities are studied as potential antimacterial and abtifungal drugs. With increasing level of resistence to currently drugs is the development of new substances very intense. Salicylanilides are a group of substances with antimicrobial activity and are also intensively studied. Based on that we were synthesized novel Schiff bases resulting from salicylic acid, respectively salicylanilides. It was concretely prepared five compounds: 5- chloro-N-{4-[phenyl(phenylimino)methyl]phenyl}-2-hydroxybenzamide, 5-bromo-N-{4-[ phenyl(phenylimino)methyl]phenyl}-2-hydroxybenzamide, 5-chloro-N-{4-[phenyl(3- chlorfenylimino)methyl]phenyl}-2-hydroxybenzamide, 5-chloro-N-{4-[phenyl(4- chlorfenylimino)methyl]phenyl}-2-hydroxybenzamide, 5-bromo-N-{4-[phenyl(4- chlorfenylimino)methyl]phenyl}-2-hydroxybenzamide. The reaction proceeded at the boiling point of the solvent, with catalytic amount of p-toluensulfonic acid. Most of the compounds were characterized by IR, H1 NMR, C13 NMR and melting point. The prepared compounds showed E/Z isomers on double bond, it is demonstrated on NMR specters.
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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....
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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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