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Multidisciplinary characterization of interactions between oestrogen hormones and their receptors during sperm capacitation.
Bosáková, Tereza ; Komrsková, Kateřina (advisor) ; Smrček, Stanislav (referee) ; Postlerová, Pavla (referee)
This doctoral thesis was focused on the multidisciplinary characterizatrion of interactions between hormones and their receptors during sperm capacitation, which is the final step in sperm maturation in mammals and the key event to achieve egg fertilization. Three oestrogenic hormones (17β-estradiol (E2), 17α-estradiol (αE2), 17α-ethynylestradiol (EE2)), which are part of environmental pollution, were selected for the study. These hormones are called endocrine disruptors as they can cause disorders of the hormonal system in animals, thereby adversely affecting physiological processes, including reproduction. A new analytical HPLC-MS/MS method was developed for monitoring of concentration changes of oestrogens (E2, αE2 and EE2) during time-dependent capacitation of mouse and rat sperm in vitro. For individual oestrogens, the concentration dependences of free, unbound hormone on the capacitation time were measured for three concentrations of individual hormones (200, 20 and 2 μg/L). The obtained concentration data were converted into values of relative concentrations, which were subjected to kinetic analysis. Kinetic models were proposed for the interaction of individual hormones with sperm, which were described by a system of differential equations with optimization of rate constants and molar...
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Cyclodextrin-drug conjugates equipped with targeting groups as anticancer agents
Lamačová, Lucie Josefa ; Jindřich, Jindřich (advisor) ; Smrček, Stanislav (referee)
This diploma thesis deals with the synthesis of conjugates of cyclodextrin with the anticancer drug 5-fluorouracil and folic acid, which works as a targeting group. 5-Fluorouracil is connected to cyclodextrin via an acid-labile linker, which is expected to be cleaved in decreased pH in the proximity of malignant tissue or in the endosome. Malignant tissue also overexpresses receptor for folic acid, and this phenomenon is used for targeted delivery of therapeutic agents. Cyclodextrins are cyclic oligosaccharides, which are known for their ability to complex various compounds into their hydrophobic cavity and increase solubility, stability and bioavailability of these compounds. A synthetic approach for the preparation of conjugate of cyclodextrin with 5-fluorouracil and folic acid was designed and the conjugate was subsequently synthesized. Key words: cyclodextrin, fluorouracil, targeting group, folic acid, drug delivery
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Effect of Nanoparticles on Plant Metabolism
Cyrusová, Tereza ; Szotáková, Barbora (advisor) ; Hnilička, František (referee) ; Smrček, Stanislav (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Mgr. Tereza CYRUSOVÁ Supervisor: prof. Ing. Barbora SZOTÁKOVÁ, Ph.D. Consultant: RNDr. Radka PODLIPNÁ, Ph.D. Title of Doctoral Thesis: Effect of Nanoparticles on Plant Metabolism Along with the expansion of nanotechnologies, which are used in many disciplines, the field of nanotoxicology has recently been developed. It deals with the negative effects of engineered nanoparticles on the environment and biota. Considerable attention has already been paid to the toxicity of nanoparticles to plants, however, the mechanisms responsible for their effects are not fully understood yet. At the same time, the possible positive effect of nanoparticles on plants has been investigated in recent years. The aim of our work was to study and evaluate the effect of nanoparticles on the growth of selected plant species and to evaluate their phytotoxicity. We focused on the study of nanoparticles in the form of metal oxides. The content of accumulated metals in germinating plants of mustard (Sinapis alba L.), in in vitro cultures of true-fox sedge (Carex vulpina L.) and the concentration of metal ions released into the culture media were measured by atomic absorption spectrometry (Cu, Fe, Mn, Zn). and inductively...
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Effect of Nanoparticles on Plant Metabolism
Cyrusová, Tereza ; Szotáková, Barbora (advisor) ; Hnilička, František (referee) ; Smrček, Stanislav (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Mgr. Tereza CYRUSOVÁ Supervisor: prof. Ing. Barbora SZOTÁKOVÁ, Ph.D. Consultant: RNDr. Radka PODLIPNÁ, Ph.D. Title of Doctoral Thesis: Effect of Nanoparticles on Plant Metabolism Along with the expansion of nanotechnologies, which are used in many disciplines, the field of nanotoxicology has recently been developed. It deals with the negative effects of engineered nanoparticles on the environment and biota. Considerable attention has already been paid to the toxicity of nanoparticles to plants, however, the mechanisms responsible for their effects are not fully understood yet. At the same time, the possible positive effect of nanoparticles on plants has been investigated in recent years. The aim of our work was to study and evaluate the effect of nanoparticles on the growth of selected plant species and to evaluate their phytotoxicity. We focused on the study of nanoparticles in the form of metal oxides. The content of accumulated metals in germinating plants of mustard (Sinapis alba L.), in in vitro cultures of true-fox sedge (Carex vulpina L.) and the concentration of metal ions released into the culture media were measured by atomic absorption spectrometry (Cu, Fe, Mn, Zn). and inductively...
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Synthesis of nucleoside analogs based on derivatives of 2-deoxy-2-fluoro- and 3-deoxy-3-fluoro-D-ribose and pyrazines
Smolka, Ondřej ; Jindřich, Jindřich (advisor) ; Smrček, Stanislav (referee)
This thesis deals with the synthesis of prodrugs based on analogs of nucleoside phosphonates derived from 6-fluoro-3-hydroxypyrazine-2-carboxamide (T-705) and 3- hydroxypyrazine-2-carboxamide (T-1105). T-705 and T-1105 act as inhibitors of an influenza RNA polymerase. Both compounds mimic naturally occurring nucleobases, so their fluorinated nucleoside phosphonates could also be biologically active. Derivatives of 2-deoxy-2-fluoro-D-ribose (2-FdR) were prepared in this work. Because of complications during the syntthesis of 3-deoxy-3-fluoro-D-ribose (3-FdR) derivatives, 5- deoxy-5-fluoro-D-xylose (5-FdX) derivatives were prepared instead. Deoxyfluorination was done after incorporation of suitable protecting groups followed by selective deprotection and phosphonate binding. Furthermore nucleosides were synthetised using silyl-Hilbert-Johnson method and their bis-POM derivattives were also prepared. Key words: favipiravir (T-705), T-1105, prodrugs, phosphonates, fluorinated nucleosides
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Effect of selected cosmetic products on estrogen formation
Drejslarová, Iva ; Hodek, Petr (advisor) ; Smrček, Stanislav (referee)
Cytochrome P450 enzymes play a key role in the metabolism of endogenous and exogenous compounds. These enzymes are involved both in biotransformation and steroid hormone biosynthesis. An important member of this family is cytochrome P450 19, aromatase, which catalyzes the final step of estrogen hormone biosynthesis, conversion of androgens into estrogens. The physiologic functions of estrogens include development of secondary sexual characteristicts, maintenance of bone mass or regulation of gonadotropin secretion. However, hormonal imbalance due to endocrine disruptors can result in development of certain cancers or impaired reproduction. Compounds with these effects include, in addition to environmetal pollutants, some drugs and cosmetic additives which people are exposed to on a daily basis. In the present study, the effect of selected perfumes and antiperspirants on the metabolic conversion of testosterone into estradiol, catalyzed by aromatase, was examined. The activity of this enzyme was detected using TLC chromatography. The experiments showed that selected antiperspirants do not affect aromatase activity. For most of the perfumes tested, only a very low aromatase inhibition was observed. Only one sample showed this effect to a higher extent. Based on the comparision of perfume...
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New method of peptide separation using electrostatic binding
Palágyi, Attila ; Jindřich, Jindřich (advisor) ; Smrček, Stanislav (referee)
The diploma thesis deals with the development of a new method of synthetic peptide separation using electrostatic binding. It deals with the development of a multi-charged anchored linker attachable to a synthetic peptide after its synthesis on solid phase. Subsequently, it investigates the separation using electrostatic binding; however, after peptide cleavage from the anchored linker and Boc deprotection with TFA, the peptide formed so strong electrostatic interactions with the cation exchanger that we were unable to recover it. The thesis is finished with discussion and method improvement proposal. Key words: peptide separation, solid-phase peptide synthesis, SPPS, electrostatic binding
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Synthesis of 9-deazaguanine derivatives as potential inhibitors of tRNA-guanine transglycosylase (TGT)
Chylíková, Barbora ; Hocek, Michal (advisor) ; Smrček, Stanislav (referee)
Shigellosis is an acute diarrheal disease caused by enterobacteria of the genus Shigella. Worldwide, these bacteria are responsible for about 1 million deaths out of 165 million cases of the disease yearly, of which children under the age of 5 from developing countries are the most vulnerable group. The enzyme tRNA-guanine transglycolase (TGT for short) has been identified as essential for the effective pathogenesis of Shigella bacteria and therefore becomes a potential target for the selective treatment of shigellosis. This bachelor thesis describes the optimization of the preparation of a key intermediate for the synthesis of potential TGT inhibitors based on 8-aryl-9-deazaguanine structure. The synthesis starts from commercially available 2,6-dichloro-9-deazapurine. The main steps of the synthesis are the hydrolysis at position 6, the nucleophilic aromatic substitution of the chlorine group for the amino group in position 2, further the iodation and the introduction of the 3-thienyl group in position 8 by Suzuki coupling.
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