|
| |
|
|
Following of acetylcholinesterase-pesticide interaction using biosensor technology
Drobík, Oto ; Opletalová, Veronika (advisor) ; Vlček, Vítězslav (referee)
FOLLOWING OF ACETYLCHOLINESTERASE-PESTICIDE INTERACTION USING BIOSENSOR TECHNOLOGY Oto Drobík Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Drug Control Organophosphorus and carbamate pesticides are toxic substances used in agriculture as insecticides. These substances are highly toxic for humans as acute poisoning can lead to death via inhibition of acetylcholinesterase. After acetylcholinesterase inhibition, accumulation of acetylcholine follows. In compliance with the thesis aims, functional electrochemical biosensor was constructed. It was based on a standard screen printed amperometric sensor with three electrodes. Herein sensors with platinum and carbon working electrode were tested. Suitable method of electrochemical assay was chosen and some the basic conditions were optimized. Kinetic parameters of enzyme reaction were assessed, too. Various methods of acetylcholinesterase capturing onto sensor were tested and compared one to each other. Paraoxon-methyl and diisopropylfluorophosphate were chosen as the representative of pesticides. Limit of detections for the both pesticides were estimated to be 10-6 - 10-5 mol/l. The prepared biosensors were compared with the standard Ellman's method based on spectrophotometry and the...
|
|
|
Synthesis and biological evaluation of purine inhibitors of phosphatidylinositol 3-kinases and related protein kinases II.
Vejrychová, Kateřina ; Opletalová, Veronika (advisor) ; Kučerová, Marta (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Drug Control Student: Kateřina Vejrychová Supervizor: Assoc. Prof. RNDr. Veronika Opletalová, Ph.D. Consultant: Mgr. Martin Andrš Title of diploma thesis: Synthesis and biological evaluation of purine inhibitors of phosphatidylinositol-3-kinases and related protein kinases II Cancer is a serious disease with an uncertain prognosis and difficult treatment. Nowadays, cancer is one of the most common causes of death worldwide. Options of therapies are evolving every year; nevertheless, we still do not have effective treatment available for all types of tumours. Patients often undergo conventional cytotoxic therapy or radiotherapy, which unfortunately have many side effects and they are not always effective. One of the highly researched ways how to make this treatment more effective is to disrupt corrective mechanisms of DNA damage, which are the essence of radiotherapy and some chemotherapeutics. For this purpose, phosphatidylinositol-3-kinase-related proteinkinases, especially DNA-dependent proteinkinase (DNA-PK) seem to be very useful, because they are highly involved in DNA repair. In this diploma thesis, 12 potential inhibitors of DNA- PK were prepared, from which 9 substances were tested alone on 9...
|
|
|
Synthesis of alkylaminoderivatives of phthalocyanines
Tomek, Ondřej ; Kopecký, Kamil (advisor) ; Opletalová, Veronika (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Drug Analysis Student: Ondřej Tomek Supervisor: PharmDr. Kamil Kopecký, Ph.D. Title of diploma thesis: Synthesis of alkylaminoderivates of phthalocyanines The aim of my diploma thesis was the synthesis and the characterization of phthalocyanine alkylaminoderivates and the comparison of their photophysical and photochemical properties with similarly substituted azaphthalocyanines. I start with the synthesis of dialkylaminodichlorophthalonitrile by the substitution of tetrachlorophthalonitrile. Then I use these derivates of tetrachlorophthalonitrile for cyclotetramerization reaction. As a result of my work, I received only diethylaminosubstituted phthalocyanines with undesirable butoxy-substituents. I was not successful in the preparation of phthalocyanines substituted with cyclic amines by the used methods. The prepared compounds were characterized by using the standard spectral methods (UV-VIS, IR, 1 H NMR, 13 C NMR, mass spectra).
|
|
|
Derivatives of Rhodanine as Potential Drugs I.
Vlčková, Martina ; Opletalová, Veronika (advisor) ; Miletín, Miroslav (referee)
Příloha 3 Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Chemistry and Drug Control Diploma paper Rhodanine derivatives as potential drugs II. Martina Vlčková Compounds containing a rhodanine motive create a perspective group of molecules that are studied as antimicrobial and antiprotozoic drugs or as substances with influence on inflammatory and proliferative processes. This paper describes the condensation of rhodanine with aromatic aldehydes in alkaline medium and the biological activity of the products: 5-[4-(dimethylamino)benzylidene]-2-thioxothiazolidin-4-one, 5-(2,4-dihydroxy- benzylidene)-2-thioxothiazolidin-4-one, 5-(4-chlorbenzylidene)-2-thioxothiazolidin- 4-one and 5-pyrazin-2-ylmethylene-2-thioxothiazolidin-4-one. These products don't show significant antifungal activity except 5-(4-chlorbenzylidene)-2-thioxothiazolidin-4-one. This substance shows some inhibition effect on Trichosporon asahii (MIC/IC80/12 h = 62.5 μmol.l-1 ), Trichophyton mentagrophytes (MIC/IC80/72 h = 15.62 μmol.l-1 ), Aspergillus fumigatus (MIC/IC80/12 h = 15.62 μmol.l-1 ) and Absidia corymbifera (MIC/IC80 /12 h = 15.62 μmol.l-1 ). The inhibition activity of these compounds on Mycobacterium tuberculosis wasn't found sufficient for further investigation. The strongest...
|
|
| |
|
|
Derivatives of Rhodanine as Potential Antifungal and Antimycobacterial Drugs
Mahmoudi Majd, Morid ; Opletalová, Veronika (advisor) ; Zimčík, Petr (referee)
MORID MAHMOUDI MAJD: Derivatives of Rhodanine as Potential Antifungal and Antimycobacterial Drugs". Diploma Thesis, Department of Pharmaceutical Chemistry and Drug Control, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, 2007 Abstract In the theoretical part of my diploma thesis some issues concerning tuberculosis and mycoses are discussed. Experimental part focused on the preparation of the following compounds 5-(2-methoxybenzylidene]-2-thioxo-1,3-thiazolidin-4-one 5-(3-methoxybenzylidene]-2-thioxo-1,3-thiazolidin-4-one 5-(4-methoxybenzylidene]-2-thioxo-1,3-thiazolidin-4-one 5-(4-bromobenzylidene]-2-thioxo-1,3-thiazolidin-4-one 5-pyridin-2-ylmethyliden-2-thioxo-1,3-thiazolidin-4-one. The compounds were prepared by the condensation of rhodanine with aromatic aldehydes in ethanol using a mixture NH4OH/NH4Cl as the catalyst. Their purity was checked by the elemental analysis and HPLC. The products were characterized by IR and NMR spectra. The susceptibility of 8 pathogenic fungal strains (Candida albicans ATCC 44859, Candida tropicalis 156, Candida krusei E 28, Candida glabrata 20/I, Trichosporon asahii 1188, Aspergillus fumigatus 231, Absidia corymbifera 272 and Trichophyton mentagrophytes 445) to these substances was determined by the microdilution broth method. No interesting...
|
|
|
Synthesis of novel blebbistatin derivatives as myosin inhibitors
Pham, Ngoc Lam ; Opletalová, Veronika (advisor) ; Zimčík, Petr (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Drug Control Student: Ngoc Lam Pham Supervisor: Assoc. Prof. RNDr. Veronika Opletalová, Ph.D. Thesis Title: Synthesis of novel blebbistatin derivatives as myosin inhibitors Myosins constitute a large and diverse superfamily of ATP-dependent motor proteins responsible for actin-based motility. Currently, based on phylogenetic analyses, myosins are classified into at least twenty four groups. The members of this superfamily are involved in several cell processes such as muscle contraction, cytokinesis, organelle transport, cell polarization and signal transduction. Thus, dysfunction and mutation of myosins can cause several diseases. Therefore, design of myosin inhibitors seems to be very attractive research field from the point of view of characterization of intracellular processes as well as development of novel targeted therapy against diseases implicating myosin dysfunction. Nowadays, one of the most well-known and widely used inhibitors of myosin is (S)-blebbistatin. This inhibitor of myosin II has many advantages, nevertheless it possesses also several limiting factors impeding the biological studies such as photosensitivity and low solubility in water. The aim of this Thesis was to...
|
|
|
Synthesis and biological evaluation of purine inhibitors of phosphatidylinositol 3-kinases and related protein kinases I.
Poledníková, Michaela ; Opletalová, Veronika (advisor) ; Jun, Daniel (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Drug Control Student: Michaela Poledníková Supervisor: Assoc. Prof. RNDr. Veronika Opletalová, Ph.D. Consultant: Mgr. Martin Andrš Title of diploma thesis: Synthesis and biological evaluation of purine inhibitors of phosphatidylinositol 3-kinases and related protein kinases I. Cancer is a group of diseases characterized by the uncontrolled, abnormal growth of cells. Anticancer chemotherapy is one of the basic methods for treatment, but its mechanism of action is not specific and targets rapidly dividing cells, including cancer cells as well as certain normal tissues. In recent years one of the most studied ways to improve cancer treatment is inhibition of DNA repair mechanisms. This process can lead to potentially higher efficacy of cytotoxic therapy and thus lower doses of cytostatic agents with benefit of less adverse side effects for the patient. Suitable candidate for this purpose is family of phosphatidylinositol 3-kinase- related protein kinases (PIKK). In this diploma thesis, sixteen purine analogs of nonselective inhibitor PIKK LY294002 were prepared. We also analyzed chemo-sensitizing properties of these newly synthesized inhibitors in combination with a chemotherapeutic agent doxorubicin in...
|
|
| |
guest ::
RSS feed.