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Neurotropic and antioxidant activity of selected species of monocotyledonous plants containing alkaloids.IV.
Hrstka, Václav ; Cahlíková, Lucie (advisor) ; Kučera, Radim (referee)
Hrstka V.: Neurotropic and antioxidative aktivity of some selected species of monocotyledonous alkaloidal plants in vitro IV, Diploma thesis, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany and Ecology, Hradec Králové 2013, 69 p. The objective of this thesis was to prepare ethanolic and alcaloidal extracts from six Daffodil's species of Amaryllidaceae family. In addition, measuring of inhibitory activity to human cholinesterases (HuAChE and HuBuChE) was included. According to results of particular extracts, identification of alcaloidal spectrum of each extract was performed using GC/MS analysis in order to evaluate inhibitory activities that had been measured. All plants described within the work were scrutinized by complete GC/MS analysis for the first time. A pure alkaloid homolycorine was isolated from the species Narcissus Sir Winston Churchilli. Its structure was identified according to its NMR spectrum and MS study. Inhibitory activity to HuAChE and HuBuChE of this alkaloid in pure form was also tested. The strongest inhibitory activity against HuAChE was detected in extract from Narcissus Flower Record with value IC50 = 5,6 ± 2,1 µg/ml. The most significant activity to both esterases had extract from Narcissus poeticus var. recurvus...
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Synthesis of new organic compounds containing chalcogens
Miltová, Lucie ; Kučera, Radim (advisor) ; Kučerová, Marta (referee)
Charles University, Faculty of Pharmacy in Hradec Kralove Department of Pharmaceutical Chemistry and Drug Analysis Candidate Lucie Miltová Supervisor doc. PharmDr. Radim Kučera, Ph.D. Consultant Prof. Dr. Claus Jacob Title of Diploma Thesis Synthesis of new organic compounds containing chalcogens A new triazole containing selenium was prepared by Huisgen 1,3-dipolar cycloaddition of alkyne and azide, known as the click reaction. Another two tetrazoles were synthesized by click reaction. Both compounds have the same structure, except the first compound is tetrazole bound to selenium, in the second compound to sulfur. Additionally, two more compounds contain the SeCN fragment and sulfur at the aromatic ring was prepared. The focus of this thesis is on the synthesis of new organic compounds containing chalcogens, specifically sulfur and selenium. Due to the presence of chalcogens in the structure, they are expected to show antioxidant, anticancer, antifungal or antibacterial effects or a combination thereof. A new triazole was synthesized and subsequently characterised by TLC, 1 H-NMR, 13 C- NMR and MS. It is suitable for future testing of biological activity. Tetrazole contains sulfur was prepared. The final product is, however, unstable and prone to rapid degradation. Using the same reaction...
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The influence of solubility and adsorption on plastic materials on transport experiments
Šilhanová, Marie ; Kučera, Radim (advisor) ; Váňová, Nela (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department: Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Student: Marie Šilhanová Supervisor: doc. PharmDr. Radim Kučera, Ph.D. Title of diploma thesis: The influence of solubility and adsorption on plastic materials on transport experiments From transport experiments on cell culture models we get valuable information about transport mechanism of drugs in organism. In vitro experiments are conducted for example on Transwell type inserts. During the experiment it was discovered that the results are not homogeneous, and the quantity of a substance in the solution decreases apparently, the reason behind this is inadequate solubility of lipophilic substances or their adsorption on the surface of plastic materials used in the experiment. Due to these problems we experience significant bias. This thesis is focused on antivirotics that did not perform well during transport experiments. First, HPLC/MS methods were developed, and they were used for concentration measurement of samples containing individual antivirotics. The drugs were tested under wide range of conditions so possible changes in effects of adsorption on plastic surfaces and solubility of drugs could be observed. The substances were divided into groups based on...
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The reduction of the nitro group using a platinum catalyst in a flow reactor
Galčan, Gabriel ; Kučera, Radim (advisor) ; Miletín, Miroslav (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis The reduction of the nitro group using a platinum catalyst in a flow reactor Diploma thesis Candidate: Gabriel Galčan Supervisor: doc. PharmDr. Radim Kučera, Ph.D. Consultant: PharmDr. Tomáš Holas, Ph.D. Flow chemistry is a relatively new solution in the production of pharmaceutical materials. This thesis is dealing with the reduction of a nitro group on an aromatic nucleus for production of the new cytostatic agent using a flow reactor. The reaction is in progress using a platinum catalyst and hydrogen, which is generated by the electrolysis of distilled water. The theoretical part is mainly concentrated on the overview of flow systems, presents important variables for the course of the reaction in the flow, and there is also the digression to the flow chemistry. The next object of attention is the use of flow reactors in the context of green chemistry, but also the future of flow systems and their limits. The practical part contains information about the construction and setting options of the flow reactor together with data about the reaction scheme and all critical impurities. Very good results were achieved with a mixture of solvents dichlormethane and methanol under...
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LC-MS/MS study of phase one in vitro biotransformation of potential drugs against Alzheimer's disease
Kuřátková, Aneta ; Kučera, Radim (advisor) ; Váňová, Nela (referee)
No treatment that would completely stop the progression of Alzheimer's disease has not been found yet. Recently used tacrine showed good results in the treatment of Alzheimer's disease, however long-term use led to chronic hepatotoxicity due to its metabolites. This master thesis deals with the compound 7-phenoxytacrine, one of the promising tacrine derivatives, which is one of the candidates for potential use in the therapy of Alzheimer's disease. Due to the formation of hepatotoxic metabolites of tacrine after the biotransformation in human liver, it appears necessary to identify the emerging metabolites of 7-phenoxytacrine molecule. Within this master's thesis in vitro biotransformation study of 7-phenoxytacrine using human liver microsomes was performed. High performance liquid chromatography with tandem mass spectrometry was used to determine the parent substance and the seventeen 7-phenoxytacrine metabolites. The analytical method showed the formation of six monohydroxylated and eleven dehydroxylated metabolites of 7-phenoxytacrine. Thus, we concluded that hydroxylation is the major metabolic reaction after in vitro microsomal biotransformation. In addition to the identification of metabolites, a quantification and microsomal stability study, including the determination of the amount of...
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Development and characterization of modified polysulfone hemodialysis membranes by means of immobilized neutrophil elastase inhibitors
Morgošová, Kristína ; Kučera, Radim (advisor) ; Holas, Ondřej (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis University of Porto Faculty of Pharmacy Department of Chemical Sciences Department of Biological Sciences Candidate: Kristína Morgošová Supervisor: assoc. prof. PharmDr. Radim Kučera, Ph.D. Consultants: prof. Maria da Conceição Branco da Silva, Ph.D. prof. Maria Alice dos Santos Silva Gomes Martins, Ph.D. Susana Maria Santos Rocha, Ph.D. Title of diploma thesis: Development and characterization of modified polysulfone hemodialysis membranes by means of immobilized neutrophil elastase inhibitors. Chronic kidney disease (CKD) is a major health and financial burden, mainly because of the costly renal replacement therapy and treatment associated. The last stage, end-stage renal disease, is associated with high morbidity and mortality rate, generally due to cardiovascular complications. Chronic inflammation is frequently present in CKD patients, which is enhanced by the long term intra-dialytic recurrent contact between blood and hemodialysis (HD) membrane and further contributes to development of atherosclerosis. Contact with the artificial material of HD membranes leads to oxidative stress and neutrophil activation with release of neutrophil serine proteases such as human...
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Modification of capillary wall by graphene for separation applications
Ptáčková, Aneta ; Lochman, Lukáš (advisor) ; Kučera, Radim (referee)
CHARLES UNIVERSITY FACULTY OF PHARMACY IN HRADEC KRÁLOVÉ Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Candidate: Aneta Ptáčková Supervisor: PharmDr. Lukáš Lochman, Ph.D. Title of thesis: Modification of capillary wall by graphene for separation applications Capillary electrophoresis (CE) is a highly efficient separation method. Substances are separated due to their different mobility in an electric field. The CE modes of operation can be modified in different ways, e.g. capillary electrochromatography or micellar electrokinetic capillary chromatography. Modification of the inner wall of the capillary is believed to help improve separation efficiency and selectivity. Graphene is carbon with a hexagonal structure in form of two-dimensional sp2 single-atom-thick sheets. Graphene seems to be a suitable material for separation application due to its excellent properties such as large surface area and affinity to aromatic ring through π-π interactions. Our work is focused on the modification of the capillary wall by graphene. One of the methods of capillary wall modification is the Layer-by-Layer method via layering of differently charged substances bounded by electrostatic forces. Another method is chemical coating employing covalent interactions. Different combinations of polymers...
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The uset of HPLC in the field of chiral separations VI.
Marvalová, Jana ; Kučera, Radim (advisor) ; Pilařová, Pavla (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department: Department of Pharmaceutical chemistry and Pharmaceutical analysis Candidate: Jana Marvalová Supervisor: doc. PharmDr. Radim Kučera, PhD. Title of Thesis: The employment of HPLC in field of chiral separations VI. Boron clusters are synthetically prepared substances that are being intensively studied in connection with Boron Neutron Capture Therapy, the substitution of phenyl rings of molecules of already known drugs and as potential inhibitors of HIV protease. Boron clusters are symmetric molecules, however, by endo- or exo-skeletal substitution, the symmetry of the cluster is disrupted and enantiomers are formed. This diploma thesis is focused on the investigation of chromatographic conditions for chiral separations of cosanes (bis(dicarbollides) and 7,8-dicarb-nido-undecaborates derivatives using high performance liquid chromatography and chiral selectors based on cellulose and amylose in reverse-phase liquid chromatography. For this purpose, columns Lux Cellulose-1 and Lux Amylose-1 were selected with chiral selectors cellulose tris(3,5-dimethylphenylcarbamate) and amylose tris(3,5-dimethylphenylcarbamate), respectively. The mobile phases were mixtures of methanol or acetonitrile with sodium perchlorate or sodium chloride...
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Usage of HPLC and UHPLC-MS/MS techniques for clinical research
Kučerová, Kateřina ; Matysová, Ludmila (advisor) ; Doležal, Rafael (referee) ; Kučera, Radim (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Analytical Chemistry Candidate: Mgr. Kateřina Kučerová Supervisor: assoc. prof. PharmDr. Ludmila Matysová, Ph.D. Consultant: assoc. prof. RNDr. Lenka Kujovská Krčmová, Ph.D. Title of Dissertation Thesis: Usage of HPLC and UHPLC - MS/MS techniques for clinical research The dissertation thesis is dealing with the extraction techniques and with development, optimization and validation of chromatographic methods for the determination of omeprazol which is drug from the group of proton pump inhibitors, and retinol as a new potential biomarker of kidney damage. The theoretical part of the thesis is focused on detailed description of the individual analytes, their clinical significance, options of determination and the matrix in which the target analytes were determined. Furthermore, the preparation of the sample before the analysis is discussed and validation recommendations related to chromatographic methods used in both pharmaceutical analysis and bioanalysis are also mentioned. In the experimental part the development, optimization and validation of UHPLC methods and their subsequent use are described in detail. The pharmaceutical-analytical part of the work describes the determination of omeprazole in new suspension preparations,...
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Development of a bioanalytical method for the determination of novel drug candidates derived from thiosemicarbazone in a biological material
Suprunová, Vlasta ; Stariat, Ján (advisor) ; Kučera, Radim (referee)
Nowadays, high-performance liquid chromatography is widely used analytical method for separation and quantification of drugs in biological material due to its high sensitivity and selectivity. HPLC is suitable for quantitative as well as qualitative analysis. 2-benzoylpyridine-4-ethyl-3-thiosemicarbazone (Bp4eT) is a potential drug from the group of thiosemicarbazones, which are currently intensively studied and developed as anticancer agents. Their specific mechanism of action, based on chelation of iron, might overcome resistance to standard chemotherapy. The aim of this study was to develop and assess essential validation parameters of an HPLC-MS/MS method for determination of Bp4eT and its main phase I metabolites in rat plasma and to utilise the method for the analysis of samples from a pilot pharmacokinetic study in rats. The separation of Bp4eT and its metabolites was achieved on chromatographic column Discovery HSC18 (75 x 4.6 mm, 3 µm) protected by the same type of guard column using the mobile phase consisting of ammonium formate and acetonitrile in ratio 40:60 (v/v). The isocratic elution and the flow rate of 0.4 ml/min were utilised. Mass spectrometer was chosen as a detector and the quantification was performed in selected reaction monitoring mode. Plasma samples were treated using the...
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