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Preparation of quarternary cationic tenzides and their evaluation
Slavětinská, Lenka ; Doležal, Martin (advisor) ; Musílek, Kamil (referee)
Preparation of quarternary cationic tensides and their evaluation. Lenka Slavětinská This thesis was focused on a synthesis of three homological series of tensides. The analogues of N-phenylethyl-N,N-dimethyl-N-alkylammoniumbromide; 3-hydroxy-1-alkylpyridiniumbromide and 4-hydroxyiminomethyl-1-alkylpyridinium- bromide were prepared. All prepared structures were confirmed by the NMR, EA and ESI-MS analysis. Their critical micellar concentration (CMC) was measured by conductometry and the reduced CMC with increasing alkyl chain was proved. The concentration scale for the measurement of micellar catalysis of p- nitrophenylcaprylate and p-nitrophenylcaprate was based on CMC outcomes. Only more lipophilic tensides were used, because their higher reactivity with chosen substrates was expected.
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Derivatives of pyrazine as potential antituberculotic drugs
Slavětinská, Lenka ; Doležal, Martin (advisor) ; Hartl, Jiří (referee)
Charles Univerzity in Prague, Faculty of Pharmacy in Hradec Králové Departemnt: Department of Pharmaceutical Chemistry and Drug Control Candidate: Mgr. Lenka Slavětinská Supervisor: Prof. PharmDr. Martin Doležal, Ph.D. Title of candidate thesis: Derivatives of pyrazine as potential antituberculotic drugs The aim of this thesis was a preparation of derivatives of pyrazine-2-carboxylic acid (POA), namely substituted anilides of 5-chloropyrazine-2-carboxylic acid with potential antituberculotic activity. In the theoretical part of this thesis, there is a short description of tuberculosis (TB) as an infectious disease. The main topic of this part are: etiology and pathogenesis of TB, epidemiology of TB, a both common and resistant TB form and a big problems with the co-infection between TB and HIV. Next part of the theory includes a therapy of TB, first and second line antituberculars as well some drugs in clinical trials. More detailed data are giving only to pyrazinamide (PZA), because its analogues are the basic topic of this thesis. There is a summary of simple structural modifications of pyrazine (in testing from 50's years of 20th century to present) and recent theories about pyrazinamide's mechanism of action. In the practical part of this thesis is presented preparation of 12 new, in the...
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Sensitizers, Acceptors and Secondary Sources of Singlet Oxygen and Their Supramolecular Complexes with Cyclodextrins
Slavětínská, Lenka
Sensitizers, Acceptors and Secondary Sources of Singlet Oxygen and Their Supramolecular Complexes with Cyclodextrins Lenka Slavětínská Disulfonated derivatives of 9,10-diphenylanthracene are known carriers of singlet oxygen. Compounds 1, 2 and corresponding endoperoxides 3, 4 form supramolecular complexes with cyclodextrins (CDs). Binding interactions were proved by UV-Vis, fluorescence and NMR spectroscopy. R1 R2 R3 O O R1 R2 R3 + 1 O2 1, 2 3, 4 R1 R2 R3 1,3 SO3Na H SO3Na 2,4 SO3Na SO3Na H O OH OH OH O O OH OH OH O OOH OH OH O O OH OH OH O O OH OH OH O O OH OH OH O O OH OH OH O CD Glu 6 7 8 Stoichiometry and binding constant Kb of complexes of 1 and 2 with CDs were determined by Job's method of continuous variations and binding isotherm analysis respectively. The modes of host-quest interaction of 1-4 with native -CD and -CD were studied by 1 H NMR and 2D NMR (ROESY). Inclusions of phenyl groups of 1-4 into the cyclodextrin cavities were found for both -CD and -CD. The mode of interaction depends on the size of the CD cavity and position of sulfo group.
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Derivatives of pyrazine as potential antituberculotic drugs
Slavětinská, Lenka ; Doležal, Martin (advisor) ; Hartl, Jiří (referee)
Charles Univerzity in Prague, Faculty of Pharmacy in Hradec Králové Departemnt: Department of Pharmaceutical Chemistry and Drug Control Candidate: Mgr. Lenka Slavětinská Supervisor: Prof. PharmDr. Martin Doležal, Ph.D. Title of candidate thesis: Derivatives of pyrazine as potential antituberculotic drugs The aim of this thesis was a preparation of derivatives of pyrazine-2-carboxylic acid (POA), namely substituted anilides of 5-chloropyrazine-2-carboxylic acid with potential antituberculotic activity. In the theoretical part of this thesis, there is a short description of tuberculosis (TB) as an infectious disease. The main topic of this part are: etiology and pathogenesis of TB, epidemiology of TB, a both common and resistant TB form and a big problems with the co-infection between TB and HIV. Next part of the theory includes a therapy of TB, first and second line antituberculars as well some drugs in clinical trials. More detailed data are giving only to pyrazinamide (PZA), because its analogues are the basic topic of this thesis. There is a summary of simple structural modifications of pyrazine (in testing from 50's years of 20th century to present) and recent theories about pyrazinamide's mechanism of action. In the practical part of this thesis is presented preparation of 12 new, in the...
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Preparation of quarternary cationic tenzides and their evaluation
Slavětinská, Lenka ; Doležal, Martin (advisor) ; Musílek, Kamil (referee)
Preparation of quarternary cationic tensides and their evaluation. Lenka Slavětinská This thesis was focused on a synthesis of three homological series of tensides. The analogues of N-phenylethyl-N,N-dimethyl-N-alkylammoniumbromide; 3-hydroxy-1-alkylpyridiniumbromide and 4-hydroxyiminomethyl-1-alkylpyridinium- bromide were prepared. All prepared structures were confirmed by the NMR, EA and ESI-MS analysis. Their critical micellar concentration (CMC) was measured by conductometry and the reduced CMC with increasing alkyl chain was proved. The concentration scale for the measurement of micellar catalysis of p- nitrophenylcaprylate and p-nitrophenylcaprate was based on CMC outcomes. Only more lipophilic tensides were used, because their higher reactivity with chosen substrates was expected.
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Sensitizers, Acceptors and Secondary Sources of Singlet Oxygen and Their Supramolecular Complexes with Cyclodextrins
Slavětínská, Lenka
Sensitizers, Acceptors and Secondary Sources of Singlet Oxygen and Their Supramolecular Complexes with Cyclodextrins Lenka Slavětínská Disulfonated derivatives of 9,10-diphenylanthracene are known carriers of singlet oxygen. Compounds 1, 2 and corresponding endoperoxides 3, 4 form supramolecular complexes with cyclodextrins (CDs). Binding interactions were proved by UV-Vis, fluorescence and NMR spectroscopy. R1 R2 R3 O O R1 R2 R3 + 1 O2 1, 2 3, 4 R1 R2 R3 1,3 SO3Na H SO3Na 2,4 SO3Na SO3Na H O OH OH OH O O OH OH OH O OOH OH OH O O OH OH OH O O OH OH OH O O OH OH OH O O OH OH OH O CD Glu 6 7 8 Stoichiometry and binding constant Kb of complexes of 1 and 2 with CDs were determined by Job's method of continuous variations and binding isotherm analysis respectively. The modes of host-quest interaction of 1-4 with native -CD and -CD were studied by 1 H NMR and 2D NMR (ROESY). Inclusions of phenyl groups of 1-4 into the cyclodextrin cavities were found for both -CD and -CD. The mode of interaction depends on the size of the CD cavity and position of sulfo group.
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Sensitizers, Acceptors and Secondary Sources of Singlet Oxygen and Their Supramolecular Complexes with Cyclodextrins
Slavětínská, Lenka ; Mosinger, Jiří (advisor) ; Němcová, Irena (referee) ; Sýkora, Jan (referee)
l. Introduction 1.1. Singlet oxygen Singlet molecular oxygen 'o, 1'Á,) has been intensively investigated by the chemists and biologists over the few decades, primarily due to its high reactivity and cytotoxity. singlet oxygen is common term for oxygen molecules in two lowest-lying excited energy states lo2 1'Á.1 and 'oz('E.) differing in occupation of HoMo orbitals, energy and lifetime. First singlet excited state 'o, (t^r) is generated, if two electrons with antiparallel spin occupy one antibonding n* orbital. The configuration of the molecular orbitals ofthe singlet excited state r02(rts) is identical to that ofthe ground state' except that the last two electrons have antiparallel spinsr'2. Singlet oxygen is short-lived' highly oxidative cýotoxic species. Its |ifetime significantly depends on type of solvent2'r. Singlet oxygen can be generated vla photosensitized reaction. The mechanism includes the formation of the sensitizer triplet state and transfer of energy to triplet oxygen leading to lo,1'Á,) formation o.''u 1see Fig. l). Singlet ox;-'een can be a|so produced by the number of chemical reactions. e.g. using H2O2/CIO' ,.r, Hrorl MoOq2- e'r. and H2o2/cao2rr systems based on disproporcionation of H2o2that leads to H2o andrO2.
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Acyclic nucleoside bis-phosphonates as potent inhibitors of 6-oxopurine phosphoribosyltransferases
Špaček, Petr ; Keough, D. T. ; Vrbková, Silvie ; Slavětínská, Lenka ; Janeba, Zlatko ; Naesens, L. ; Edstein, M. D. ; Chavchich, M. ; Wang, T. H. ; de Jersey, J. ; Guddat, L. W. ; Hocková, Dana
Hypoxanthine-guanin-(xanthine) phosphoribosyltransferase (HG(X)PRT) is critical for the survival of malarial parasites Plasmodium falciparum and Plasmodium vivax. These parasites rely on HG(X)PRT to make 6-oxopurine nucleoside monophosphates. Specific acyclic nucleoside phosphonates (ANPs) inhibit HG(X)PRT and thus have an anti-plasmodial activity. Crystal structures of human HGPRT in complex with several ANP-based inhibitors suggested that attachment of the second phosphonate group which could occupy the pyrophosphate binding site may lead to increased affinity of these compounds.
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Pyrrolidine nucleotides conformationally constrained via hydrogen bonding
Pohl, Radek ; Poštová Slavětínská, Lenka ; Rejman, Dominik
Conformation of pyrroPME nucleotide analogues was studied by means of NMR at different pD values in D2O solutions. Surprisingly, two stable conformers were found at pD > 9 for both cis and trans configurations and their ratio depended on the acid-base properties of nucleobase attached to pyrrolidine ring. The results of conformational analysis suggest that the conformation of the pyrrolidine ring is locked via intramolecular hydrogen bond between negatively charged phosphonate oxygen atom and protonized pyrrolidine nitrogen.
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