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Synthesis and Study of New Unsymmetrical Azaphthalocyanines bearing azathiocrown ether for cation binding
Šeminská, Patrícia ; Nováková, Veronika (advisor) ; Miletín, Miroslav (referee)
1 ABSTRACT Charles University, Faculty of Pharmacy in Hradec Kralove Department: Department of Biophysics and Physical Chemistry Candidate: Patrícia Šeminská Supervisior: doc. PharmDr. Veronika Nováková, Ph.D. Consultant: PharmDr. Lukáš Lochman, Ph.D. Title of thesis: Synthesis and Study of New Unsymmetrical Azaphthalocyanines bearing azathiocrown ether for cation binding Azaphthalocyanines (AzaPc) are planar macrocyclic compounds, which are aza- analogues of synthetic phthalocyanine dyes. AzaPc, due to their system of conjugated double bonds, show interesting photophysical properties such as fluorescence emission and absorption in the red area of the spectrum, which is suitable for biological applications. These properties depend on character of peripheral substituents and central metal cation. The attachment of alkylamine group enables intramolecular charge transfer (ICT), that causes efficient quenching of fluorescence (non-fluorescent OFF state of the sensor), and leads to decrease of fluorescence quantum yield to zero. Blocking of ICT is used in development of new fluorescent sensors for metal cations, in which metal cation is coordinated into recognition moiety (e.g. azacrown ether) of the sensor. It results in a significant increase of fluorescence (fluorescent ON state of the sensor). Preparation of...
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Dietary prevention of type 2 diabetes mellitus
Nováková, Veronika ; Flekač, Milan (advisor) ; Mikeš, Ondřej (referee)
This thesis deals with dietary prevention of type 2 diabetes mellitus. The first chapters of the thesis deal with general information about diabetes mellitus. The chapters focus on the classification, epidemiology, clinical manifestation, complications, diagnostics of diabetes mellitus and pathogenesis of type 2 diabetes mellitus. The subsequent chapters describe prediabetes, obesity and metabolic syndrome. The conclusion of the theoretical section is devoted to the prevention of type 2 diabetes mellitus. The prevention is focused on non-pharmacological measures with an emphasis on dietary influences. The practical part is based on anonymous quantitative research in the form of an Internet quastionaire survey, which focuses on the prevention of type 2 diabetes mellitus. The main goal was to find out about the public's awareness of dietary effects on type 2 diabetes mellitus. The secondary objectives examine the awareness of the worlwide increase of diabetics and whether the respondents consider sugar to be the cause of type 2 diabetes mellitus and attach greater importance to healthy lifestyle or pharmacological measures in prevention. The survey results relating to dietary influences were not very satisfactory and respondents' poor awareness regarding prevention was reflected, for example in...
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Synthesis of azaphthalocyanine quenchers of fluorescence for intrastrand binding to oligonucleotides
Machan, Matěj ; Nováková, Veronika (advisor) ; Miletín, Miroslav (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department: Department of Pharmaceutical chemistry and Pharmaceutical analysis Candidate: Matěj Machan Supervisor: doc. PharmDr. Veronika Nováková, Ph.D. Title of thesis: Synthesis of novel azaphthalocyanines working as dark quenchers suitable for binding to the middle of an oligonucleotide chain Azaphthalocyanines (AzaPcs) are analogues of well-known phthalocyanines with benzene rings replaced for pyrazine ones. AzaPcs can be used in many applications due to their interesting spectral and photophysical properties, e.g. as photosensitisers in photodynamic therapy or as fluorescence sensors. The alkylamino substituted AzaPcs can be used as dark quenchers of fluorescence in mono-labeled DNA hybridization probes (FRET probes) or double-labeled probes as well. The AzaPcs for this application have typically three quarters identical (bearing alkylamino groups responsible for quenching of fluorescence) and the last quarter is modified with a functional group for attaching to oligonucleotide probe. The goal of this project was to synthesize unsymetrical AzaPc with a T-shape functional group carrying two hydroxy groups that can be used for attaching to oligonucleotide probe. The synthesis consisted of preparation of appropriately substituted...
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Derivatives of quinoxaline-2-carboxylic acid as potential antimicrobial compounds
Bouz, Sarah ; Zitko, Jan (advisor) ; Nováková, Veronika (referee)
(ENGLISH) Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Candidate: Sarah Basem Bouz Supervisor: PharmDr. Jan Zitko, Ph.D. Title of diploma thesis: Derivatives of quinoxaline-2-carboxylic acid as potential antimicrobial compounds Despite the presence of well-established treatment plan, tuberculosis remains the number one killer of infections according to WHO. One of the reasons behind this failure in eradicating this infection is drug resistance. This fact potentiates worldwide efforts to develop new antituberculars. As part of our long-term research on pyrazine derivatives, we prepared a series of N-substituted quinoxaline-2-carboxamides, refer to fig. below. Quinoxaline-2-carboxylic acid was activated by oxalyl chloride and reacted with different anilines or benzylamines in the presence of pyridine at room temperature, overnight with stirring, and then obtained crudes were purified with flash chromatography. Final products were evaluated for in vitro antimicrobial activities against six mycobacterial strains, eight fungal stems, along with four gram positive and four gram negative bacteria of clinical importance. The most promising compound among all with broad spectrum of antimycobacterial activity (MICMtbH37Ra = 3.91...
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Music Therapy and use for disabled children
NOVÁKOVÁ, Veronika
The thesis contains a theoretical and a practical part. The theoretical part deals with a concept and a definition of music therapy, history, aims, methods of music therapy and also organisations where music therapy is done. The thesis deals with connection of music therapy and children with disabilities. The topic of disability is described in several categories. It lists the types of disabilities, connection between disabled children and music therapy. It also deals with a funcion of a music therapist and it inroduces different therapists who work with us. The practical part contains my personal project, which consists of 3 lesson in length of 45 minutes each. I took advantage of the fact that in my surrounding there is a disabled child and I organized lessons of music therapy with him.
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Physico-Chemical Properties of Drugs
Tomanová, Pavla ; Kubíček, Vladimír (advisor) ; Nováková, Veronika (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of biophysics and physical chemistry Author: Pavla Tomanová Supervisor: Ing. Vladimír Kubíček, CSc. Thesis title: Physico-Chemical properties of drugs This thesis deals with measuring dissociation constants (the pKa value) and the lipophilicity of nitrogenous heterocycle derivatives produced at the Faculty of Pharmacy in Hradec Králové. Two methods were used to determine the pK value: potentiometric titration and spectrophotometry. Potentiometric titration almost invariably produced relatively exact results, however the results of pK value obtained by spectrophotometry were sometimes difficult to replicate. Dissociation constants were compared on the basis of the method applied, and also with the theoretically determined dissociation constant calculated by means of the ChemDraw Ultra 12.0 software. The results obtained by the two experimental methods turned out to be very similar, corresponding to the theoretical pK value. Lipophilicity is another essential property of drugs tested in the preclinical stage. It specifies the aqueous or lipophilic phase affinity of a drug, substantially affecting the drug's ADMET in organism. Lipophilicity was determined on the basis of capacity factor value identified by RP-HPLC measurement using...
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Cationic surface active compounds and evaluation of its properties
Pekařová, Kateřina ; Nováková, Veronika (advisor) ; Kuchařová, Monika (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biophysics and Physical Chemistry Consultant: PharmDr. Jan Marek, Ph.D. Supervisor: doc. PharmDr. Veronika Nováková, Ph.D. Student: Kateřina Pekařová Title of Thesis: Cationic surface active compounds and evaluation of its properties Quaternary ammonium salts are used as surfactants in many branches of the food, pharmaceutical and chemical industries. The basic properties of these substances were studied in the thesis. The critical micellar concentration of the homologous series of five substances was determined using the conductometric method. The theory of declining critical micellar concentration with the increasing length of the side alkyl chain has been verified. The hydrolytic activity of two commonly used cationic surfactants benzalconium chloride and benzoxonium chloride for the decomposition of the organophosphorus pesticide fenitrothion was tested. For these two substances, the effect of pH and temperature changes was evaluated. The influence of tenside concentration was also monitored. Benzoxonium chloride at 50 řC and pH 11was found as the most effective hydrolytic catalyst for the decomposition of the organophosphorus pesticide fenitrothione.
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Determination of the fatty acids spectrum in patients undergoing treatment with taxanes
Kuříková, Barbora ; Kuchařová, Monika (advisor) ; Nováková, Veronika (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biophysics and Physical Chemistry Author of Diploma Thesis: Bc. Barbora Kuříková Supervisor of Diploma Thesis: Mgr. Monika Kuchařová, Ph.D. Consultant: prof. MUDr. Zdeněk Zadák, CSc. Title of Diploma Thesis: Determination of the fatty acids spectrum in patients undergoing treatment with taxanes The diploma thesis deals with the determination of fatty acids spectrum in erythrocytes in patients treated with taxanes. The theoretical part describes general features of fatty acids, their synthesis and degradation. Then it is focused on the topic of breast cancer, taxane treatment and negative side effects associated with taxane treatment, especially polyneuropathy. The gas chromatography, which is commonly used in practice, is also described in this part. The experimental part is divided into three parts. The first part describes working process, chromatographic analysis and evaluation of this analysis. In the second part there is comparing of spectrum of fatty acids of patients without and with polyneroupathy. And in the last part there is a comparing of spectrum of fatty acids of patients before taxane treatment, closely after treatment and about month after the treatment. Results of the experimental part are evaluated at the end...
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MicroRNA expression in glucocorticoid-treated patients with systemic autoimmune
Uher, Martin ; Kuchařová, Monika (advisor) ; Nováková, Veronika (referee)
Rheumatoid arthritis is the most common joint disease of autoimmune origin. It is accompanied by inflammatory conditions that lead to irreversible changes in the joints, their deformities ending with permanent disability. Treatment of the disease involves routine regimens, surgical, as well as pharmacological treatment, which is necessary for advanced forms. Glucocorticoids play an important role in the therapeutic intervention in the course and progression of the disease. In spite of their anti-inflammatory effect, which is a key to improving the condition of the patient, they have a number of side effects in the long term- use. In this study, we have focused on the impact of these drugs on microRNA expression changes in arthritic patients treated with pulsed doses of glucocorticoids. MicroRNAs are nowadays widely studied due to their possible use as biomarkers in monitoring disease progression and the effect of treatment. MiRNA expression analysis was performed by quantitative real-time PCR array of 754 miRNAs with reverse transcription using stem-loop primers that allow amplification of short sequences that microRNAs are. Data analysis revealed 29 miRNAs differentially expressed at the significance level p ≤ 0.05, 14 miRNAs were at significance level p ≤ 0.025 (respectively 7 miRNAs at p ≤ 0.005...
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