|
HPLC analysis of drugs and drug candidates in biological material
Luňáková, Veronika ; Kovaříková, Petra (advisor) ; Mokrý, Milan (referee)
High-performance liquid chromatography (HPLC) is currently one of the most progressive separation methods, permitting, simultaneously, both quantitative and qualitative analysis. An important area for the utilisation of HPLC is the identification of drugs and their metabolites in biological materials. This study was focused on the development of chromatographic conditions appropriate for HPLC analysis of two new potential drugs derived from aroyl-hydrazone, HNAF-INH and 4,6DAR-INH, in biological material and its subsequent application in the assessment of the stability of these substances in plasma. Analysed chelators were prepared by the modification of the structure of salicylaldehyde isonicotinoyl hydrazone (SIH) with the purpose of improving the stability of the substance in plasma. As a suitable stationary phase the HPLC column LiChroCART® HPLC - cartridge LiChrospher®100 RP - 18e (15μm) with the pre-column LiChroCART® 4-4 Purospher® RP - 18 (5μm) was chosen. The mobile phase in this case represented by a HNAF-INH compound: phosphate buffer (0,01 mol/l aqueous solution of NaH2PO4 · 2 H2O with 2 mmol/l EDTA, pH 3) : methanol, 42:58 (v/v). The temperature in the column was 25řC, the flow rate 1,0 ml/min and UV detection was performed at 288 nm; SIH was used as an internal standard. The mobile...
|
|
Investigation of Biologically Active Plant Secondary Metabolites by Antioxidant and Anti-Aggregative Tests
Řeháková, Zuzana ; Jahodář, Luděk (advisor) ; Semecký, Vladimír (referee) ; Grančai, Daniel (referee)
The effort to find compounds with significant antioxidant properties and with some other therapeutically useful biological activity (e.g. anti-platelet activity) from the wide group of sturcturally different naturally occuring compouds (or plant extracts) or their synthetic derivatives, was the purpose of this work. Radical Scavenging activity of tested compounds or plant extracts was measured by modified DPPH test use program SIA (sequential injection analysis). Singificant radical scavenging activity exhibited polyfenols, namely gallic acid (EC50= 0,0025 ± 0,002 mg/ml) and ethyl-gallate (EC50= 0,0038 ± 0,001 mg/ml). Also the pure latex of Croton lechleri exhibited significantly radical scavenging activity (EC50=0,0347 ± 0,018 mg/ml). From the group of tested methylcoumarins, the excelent antioxidant aktivity exhibited ortho-dihydroxy-4-methylcoumarins, espicially 7,8-dihydroxy-4- methylcoumarin and its derivatives (EC50= 24,9 ± 2,7 μM). Further was the antioxidant activity tested by FRAP methods modified to used micropalates P 400 μl. This spectrofothometric method based on ability of compounds to reduce Fe3+ to Fe2+, confirmed the antioxidant activity of ortho-dihydroxy-4-methylcoumarins. The antiplatelet activity of pure compounds and herbal extracts was assayed in vitro on the model of human...
|
|
Derivatives of pyrazine as potential antituberculotics
Osička, Zdeněk ; Doležal, Martin (advisor) ; Kučerová, Marta (referee)
Mgr. Zdeněk Osička: Pyrazine Derivatives as potential antituberculous drugs I have focused on the synthesis of compounds from the class amides of substituted pyrazinoic acid in my Pharmacy Doctor Thesis. Series of compounds were prepared by the reaction of pyrazinoic acid chloride with corresponding amines. Synthesis underwent in two steps. Final compounds were characterized by the melting point, TLC, elementary analysis, 1H a 13C NMR and IR. All compounds were liable in vitro testing on their biological activity - antimycobacterial, antifungal and antibacterial. In the group of antituberculosis testing the activity grew up from the least to the most lipophility compound.
|
|
Synthesis of Neurosteroids: Modulators of NMDA Receptor
Šťastná, Eva ; Chodounská, Hana (advisor) ; Klinotová, Eva (referee) ; Drašar, Pavel (referee) ; Hampl, Richard (referee)
Charles University in Prague Faculty of Science Department of Organic and Nuclear Chemistry Karlova Universita v Praze Přírodovědecká fakulta Katedra organické chemie a jaderné chemie Mgr. Eva Šťastná Synthesis of Neurosteroids: Modulators of NMDA receptor Syntéza neurosteroidů: modulátorů NMDA receptoru PhD. Thesis Abstract Autoreferát disetační práce Praha 2009 Prague, 2009 Scientific Presentations and Posters Papers Šťastná E.: Diazomethane (CH2N2). Synlett, 2007,15,2454. Stastna E., Chodounska H., Pouzar V., Kapras V., Borovska J, Cais O., L Vyklicky L.: Synthesis of C3, C5, and C7 pregnane derivatives and their effect on NMDA receptor responses in cultured rat hippocampal neurons. Steroids 2009, 74, 256-263. Kapras V., Šťastná E., Chodounská H., Pouzar V., Krištofíková Z.: Preparation of steroid sulfamates and their interaction with GABAA receptor. Coll. Czech. Chem. Comm., submitted, manuscript number CCCC/2008/000187. Eignerová B., Slavíková B., Buděšínský M., Stastna E., Kotora M.: Synthesis of Fluorinated Brassinosteroids Based on Alkane Cross-Metathesis and Preliminary Biological Assessment. J. Org. Chem., under revision, manuscript number jo-2009- 002079. Patents Stastna E., Chodounska H., Cais O., Vyklicky L., Kapras V., Pouzar V., Kohout L.: Steroidní anionické sloučeniny, způsob...
|
|
The anti-inflammatory effects of natural and synthetic triterpenoid coumpounds.
Spáčilová, Pavla ; Hajdúch, Marián (advisor) ; Džubák, Petr (referee)
The thesis is focused on in vitro testing of biological activities related to inflammation, such as inhibition of nitric oxide production and inhibition of reactive oxygen species formation in activated cells. 65 triterpenoid derivatives were tested in experimental section of the thesis for nitric oxide sythesis inhibition in B10R cells stimulated with lipopolysaccharide. 15 compounds showed terapeutic index value higher than 4, including three compounds which showed IC50 value lower than 10 μmol/l. 115 triterpenoid compounds were tested for inhibition of reactive oxygen species formation in RAW 264.7 cells stimulated with opsonized zymosan. Two compounds showed IC50 value lower than 10 μmol/l. None of 115 tested compounds showed NO·-scavenging activity. Four compounds showed a moderate O2-·-scavenging activity. Powered by TCPDF (www.tcpdf.org)
|
|
Chalcones and their analogues as potential drugs.
Chlupáčová, Marta ; Hartl, Jiří (advisor) ; Kuneš, Jiří (referee) ; Čižmárik, Jozef (referee)
1 SUMMARY This dissertation thesis deals with searching for potential drugs, particularly with preparation and biological activity study of natural compounds derivatives - chalcones. The work includes preparation of intermediates - 5-alkylated pyrazin-2-carbonitriles and 1-pyrazinyl-2-ethanones. Substituted chalcones, several series of pyrazine analogues of chalcones and Michael adducts of chalcones with different thiols were prepared as final products. In this part of the work, known reaction methodologies were used. Products were identified by melting point, resp. boiling point, IR, NMR spectra. Their purity was checked by elemental analysis. In the case of liquids, elemental analysis could not be performed, and MS spectra were recorded instead. In total were prepared 22 intermediates (9 of them have been described in our department) 62 final products (19 of them have been already described) 1 by-product 57 Unknown compounds were prepared. Synthesis of 12 compounds was not successful. The final products were tested for their antimycobacterial, antifungal, antialgal, and antiaggregating effects. The chalcones were examined for the ability to inhibit one of the cysteine protease - papain and this part of the work continued in a preliminary kinetic study of reaction addition of chalcones with thiol-...
|
|
Acetylpyrazines as intermediates for the synthesis of biologically active derivative of pyrazine III.
Zobalová, Dana ; Opletalová, Veronika (advisor) ; Palát, Karel (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Drug Analysis Candidate Mgr. Dana Honcová-Zobalová Consultant RNDr. Veronika Opletalová, Ph.D. Title of Thesis Acetylpyrazines as intermediates for the synthesis of biologically active derivatives of pyrazine III. The rigorous thesis is aimed at the preparation of 5-alkylpyrazin-2-carbonitriles, 5-alkyl-2-acetylpyrazines and their thiosemicarbazones and N,N-dimethylthiosemicarbazones. N,N-dimethylthiosemicarbazone of acetophenone was prepared for comparison. Theoretical part deals with the structure and properties of thiosemicarbazones and their biological effects. The following compounds were prepared and characterized during experimental work: 5-isopropylpyrazin-2-carbonitrile 5-pentylpyrazin-2-carbonitrile 5-hexylpyrazin-2-carbonitrile 5-heptylpyrazin-2-carbonitrile 1-(5-isopropylpyrazin-2-yl)ethan-1-one 1-(5-pentylpyrazin-2-yl)ethan-1-one 1-(5-hexylpyrazin-2-yl)ethan-1-one 1-(5-heptylpyrazin-2-yl)ethan-1-one 1-(5-hexylpyrazin-2-yl)ethan-1-one thiosemicarbazone 1-pyrazin-2-ylethan-1-one N,N-dimethylthiosemicarbazone 1-(5-pentylpyrazin-2-yl)ethan-1-one N,N-dimethylthiosemicarbazone 1-(5-hexylpyrazin-2-yl)ethan-1-one N,N-dimethylthiosemicarbazone ...
|
| |
|
Studies on NKR-P1A and NKR-P1B receptors expressed in eukaryotic organisms
Ivanova, Lyubina ; Rychlovský, Petr (referee) ; Bezouška, Karel (advisor)
NK (natural killer) cells, with their ability to identify antigens and extraneous substances, available in the organism through various moleculary receptors, are an important component of the immune system. The NKR-P1A and NKR-P1B proteins belong to the lectin receptors of natural killer cells. Primary ligands of lectin receptors comprise terminal oligosaccharides of glycoproteins on the surface of target (e.g. tumor) cells. The interaction between carbohydrate structures on the surface of antigens and their binding partners on NK receptors is followed by triggering the effector function of NK cells against the targets. The NK cells and NK receptors findings and their interactions with ligands are greatly utilized in the treatment of cancer, viral and autoimmune diseases. Heterologous protein production in the eukaryotic organism brings a lot of advantages. Unlike the prokaryotic organism, the methylotrophic yeast Pichia pastoris has the capability of performing many posttranslational modifications resulting in production of biological active protein molecule. Usually, the P. pastoris expression system disposes of high level protein expression and is also generally regarded as being faster, easier, and less expensive to use than expression systems derived from other eukaryotes. In this thesis, I...
|
|
Phosphanucleosides containing 1-hydroxymethylphospholane 1-oxide ring
Páv, Ondřej ; Zborníková, Eva ; Buděšínský, Miloš ; Rosenberg, Ivan
Novel phosphanucleosides containing 1-hydroxymethylphospholane 1-oxide ring were synthesized as compounds with potential biological activity. A ring-closing metathesis was employed to prepare a phospholene precursor, which was then converted into either 4-azido-3-hydroxy-1-hydroxymethylphospholane 1-oxide or 3-azido-1- hydroxymethylphospholane 1-oxide derivatives. Subsequently, nucleobase was introduced using a nucleobase construction. The biological activity of prepared compounds was evaluated.
|
guest ::
