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Sulfates as phase II metabolites of natural phenolic compounds
Hetman, Anastasiia ; Mladěnka, Přemysl (advisor) ; Siatka, Tomáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Anastasiia Hetman Supervisor: Assoc. Prof. Přemysl Mladěnka, PharmD., Ph.D. Co-supervisor: Assoc. Prof. Kateřina Valentová, Ph.D. Title of diploma thesis: Sulfates as phase II metabolites of natural phenolic compounds Natural monophenolic compounds, which both occur in plants and are formed during gut microbiota metabolism of polyphenols, are absorbed and pass through phase II metabolism. This results in the formation of various conjugated metabolites, such as sulfates, whose biological activity was not studied as yet. This work focused on the preparation and isolation of pure sulfated metabolites of phenolic compounds, namely 4- methylcatechol, protocatechuic, homoprotocatechuic, and 2,3,4-trihydroxybenzoic acid, and phloroglucinol, using the aryl sulphotransferase from Desulfitobacterium hafniense. As a result, two sulfated products of sufficient purity were prepared, namely 4- methylcatechol-O-sulfate (an inseparable mixture of 4-methylcatechol-2-O-sulfate and 4- methylcatechol-1-O-sulfate) and phloroglucinol-O-sulfate. Their antioxidantactivity was evaluated and compared with the activity of the parent compounds using the following six in vitro tests: DPPH (1-diphenyl-2-picrylhydrazyl) and...
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Copper chelating properties of flavanones
Kantorová, Tereza ; Mladěnka, Přemysl (advisor) ; Spilková, Jiřina (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Departmet of Pharmacology and Toxicology Candidate: Tereza Kantorová, MSc. Consultant: Assoc. Prof. Přemysl Mladěnka, Pharm.D.,PhD. Title of the Rigorous Thesis: Copper chelating properties of flavanones Copper is an essential trace element playing an essential role in our body. As part of couproenzymes, it is involved in many physiological processes. However, at the same time, it also poses a certain risk to the human body. Free copper has the ability to potentiate the formation of reactive oxygen species and thus to promote oxidative stress. Therefore, copper homeostasis must be carefully regulated. Flavanones belong to one of the subclasses of flavonoids. These natural substances are very interesting from a scientific point of view due to their possible various pharmacological effects. In this work, we focused on their copper-chelating properties. Flavanones, which are expect to possess a low potential for side effects, could find application as copper chelators and thus expand the current therapeutic modalities for some diseases associated with copper imbalance (e.g. Wilson's disease, tumors). Four selected flavanones (hesperetin, hesperidin, naringenin and naringin) were tested for their ability to chelate copper ions using two...
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Membrane endoglin and its role in pathogenesis of endothelial dysfunction in vitro
Vicen, Matej ; Nachtigal, Petr (advisor) ; Mladěnka, Přemysl (referee) ; Štěrba, Martin (referee)
Charles University, Faculty of Pharmacy in Hradec Kralove Department of Biological and Medical Sciences Candidate: M. Sc. Matej Vicen Supervisor: Prof. PharmDr. Petr Nachtigal, Ph.D. Title of Doctoral Thesis: Membrane endoglin and its role in pathogenesis of endothelial dysfunction in vitro Membrane endoglin (Eng) is a transmembrane glycoprotein that acts as a co-receptor in the transforming growth factor β (TGFβ) signalling cascade. Its expression and function have been extensively studied predominantly in relation to endothelial function under various pathological conditions, including hypercholesterolemia and atherogenesis. However, its role in the development of endothelial dysfunction remains controversial. Eng contributes to the formation of nitric oxide (NO) and is crucial in in vivo conditions for the development of the cardiovascular system and especially the heart. On the other hand, it may play an important role in inflammatory adhesion and transmigration of leukocytes to the endothelium, thus contributing to the development of endothelial dysfunction as the first stage of atherogenesis. Experiments on endothelial cells isolated from various blood vessels are used to study short-term effects of substances and drugs on the endothelium. One of the effects studied in endothelial cell...
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Copper reducin properties of a series of xanthe-3-ones
Kopková, Nikola ; Mladěnka, Přemysl (advisor) ; Němečková, Ivana (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Candidate: Nikola Kopková, MSc Consultant: Assoc. Prof. Přemysl Mladěnka, PharmD., Ph.D. Title of diploma thesis: Copper reducing properties of a series of xanthen-3-ones Key words: copper, reduction, xanthene-3-one, homeostasis Copper is present as a trace element in all tissues and is essential in cellular respiration, in the biosynthesis of neurotransmitters, for the scavening of reactive oxygen species, and is also a cofactor for various enzymes. Disruption of homeostasis can lead to liver and CNS damage, and tumor formation. Typical examples of an imbalance in copper homeostasis represents Wilson and Menkes disease. Xanthene derivatives are biologically active compounds with a possible broad therapeutic spectrum. Some of these derivatives have antitumor, antipyretic, immunomodulatory, antioxidant and other positive biological activities. The aim of this work was to determine whether 2,6,7-trihydroxyxanthen-3-one derivatives have the ability to reduce cupric ions and possibly to detect the effect of various substituents on this ability. As a methodology, a spectrophotometric method based on bathocuproindisulfonic acid as an indicator was used. Ten compounds were tested at different pH values. All...
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Medicinal Plants Used in the Treatment of Cardiovascular Disorders in the Czech Republic - Overview and Consumption Analysis in Years 2015 - 2019
Dubánková, Marianna ; Macáková, Kateřina (advisor) ; Mladěnka, Přemysl (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmacognosy Candidate RNDr. Mgr. Marianna Dubánková Consultant doc. Ing. Kateřina Macáková, PhD. Title of Thesis Medicinal Plants Used in the Treatment of Cardiovascular Disorders in the Czech Republic - Overview and Consumption Analysis in Years 2015 - 2019. Medicinal plants still hold their strong position in the therapy of various human diseases, even in the modern era. Seven medicinal plants long known for their use in the treatment of cardiovascular disorders were chosen for this thesis, namely Allium sativum L. (garlic), Crataegus spp. (hawthorn), Digitalis spp. (foxglove), Leonurus cardiaca L. (motherwort), Olea europaea L. (olive), Nigella sativa L. (black cumin), and Viscum album L. (European mistletoe). Their beneficial effects on the cardiovascular system (antioxidant, cardioprotective, vasorelaxant, antiatherosclerotic, antihypertensive, and lipid-lowering actions) were reviewed with an emphasis on information concerning humans. When possible, the mechanism explanation, results of clinical trials, and established dosage range for the respective fields of action are presented. The consumption analysis of the preparations containing the abovementioned medicinal plants was conducted with a total number of...
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Soluble endoglin role in the pathogenesis of endothelial dysfunction
Vitverová, Barbora ; Nachtigal, Petr (advisor) ; Vrablík, Michal (referee) ; Mladěnka, Přemysl (referee)
Charles University, Faculty of Pharmacy in Hradec Kralove Department of Biological and Medical Sciences Candidate: Msc. Barbora Vitverova Supervisor: prof. PharmDr. Petr Nachtigal, Ph.D. Title of Doctoral Thesis: Soluble endoglin role in the pathogenesis of endothelial dysfunction The endothelium is a major regulator of vascular homeostasis and exerts a number of vasoprotective effects, including production of vasodilating agents, suppression of smooth muscle cell growth, or inhibition of inflammatory responses. Most of these effects are mediated by nitric oxide (NO), the most effective endogenous vasodilator. Decreased NO production or its activity is a hallmark of endothelial dysfunction leading to an impaired endothelial-dependent vasodilation. Endothelial dysfunction is the first and key step in the development of atherosclerosis and can be detected before structural changes in the vessel wall. Atherosclerosis is a complex inflammatory disease underlying many cardiovascular disorders including ischemic heart disease and represents the major cause of morbidity and mortality in developed countries. Statins are drugs of choice in the treatment of atherosclerosis and ischemic heart disease, which have been shown to reduce LDL cholesterol levels and modulate endothelial function with their...
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Study of interactions of antiviral drugs with selected placental transporters
Karbanová, Sára ; Štaud, František (advisor) ; Kacerovský, Marian (referee) ; Mladěnka, Přemysl (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Sára Karbanová, MSc. Supervisor: prof. PharmDr. František Štaud, Ph.D. Consultant: doc. PharmDr. Lukáš Červený, Ph.D. Title of Dissertation Thesis: Study of interactions of antiviral drugs with selected placental transporters The backbone of HIV treatment in pregnant women is the combination antiretroviral therapy which effectively suppresses the viral proliferation in maternal blood circulation. One of drugs in this therapy regimen should be a molecule with high placental transfer to assure the prophylaxis of viral transfer to fetus. There is no approved guideline for pharmacotherapy of pregnant women infected with hepatitis C (HCV), however recent evidence suggests that lowering the maternal viral load could correlate with lower likelihood of HCV transmission to the fetus. To assure and further develop the effective and safe pharmacotherapeutic approaches for treatment of HIV and HCV in pregnancy with respect to fetal safety, it is essential to understand mechanisms of placental transfer of anti(retro)viral drugs. In this Dissertation thesis we focused on molecules derived from nucleosides (anti-HIV abacavir, emtricitabine, zidovudine, tenofovir disoproxil fumarate and anti-HCV...
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Zinc - chelating activity of selected novel chelators from 4-acylpyrazol-5-one group
Nováková, Jana ; Mladěnka, Přemysl (advisor) ; Kučerová, Marta (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Jana Nováková, MSc. Consultant: Assoc. Prof. Přemysl Mladěnka, PharmD., Ph.D. Co-consultant: Václav Tvrdý, MSc. Title of thesis: Zinc-chelating activity of selected novel chelators from 4-acylpyrazol-5-one group Zinc plays a key role in many physiological functions in the human body. In case of increased concentrations of zinc in the body, a number of pathological manifestations may occur. In less severe cases, gastrointestinal discomfort and nausea can occur while in a worse case, cardiovascular failure can develop. After the diagnosis of zinc intoxication is confirmed, the chelation therapy is used. Its principle is based on the formation of complexes with excessive metal and their excretion. Substances from the group 4-acylpyrazol-5-ons were previously shown to be strong iron chelators. The aim of this thesis was to test the ability of these substances the chelate zinc and determine the structure-activity relationship. Based on the obtained results, it can be concluded that most of the tested 4-acylpyrazol-5-ons were almost inactive or showed ability to chelated zinc ions only at very high excess over Zn2+ . The most effective substances were H2QPyQ and H2Q4Q. However, each of them...
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Membrane endoglin and its role in pathogenesis of endothelial dysfunction in vitro
Vicen, Matej ; Nachtigal, Petr (advisor) ; Mladěnka, Přemysl (referee) ; Štěrba, Martin (referee)
Charles University, Faculty of Pharmacy in Hradec Kralove Department of Biological and Medical Sciences Candidate: M. Sc. Matej Vicen Supervisor: Prof. PharmDr. Petr Nachtigal, Ph.D. Title of Doctoral Thesis: Membrane endoglin and its role in pathogenesis of endothelial dysfunction in vitro Membrane endoglin (Eng) is a transmembrane glycoprotein that acts as a co-receptor in the transforming growth factor β (TGFβ) signalling cascade. Its expression and function have been extensively studied predominantly in relation to endothelial function under various pathological conditions, including hypercholesterolemia and atherogenesis. However, its role in the development of endothelial dysfunction remains controversial. Eng contributes to the formation of nitric oxide (NO) and is crucial in in vivo conditions for the development of the cardiovascular system and especially the heart. On the other hand, it may play an important role in inflammatory adhesion and transmigration of leukocytes to the endothelium, thus contributing to the development of endothelial dysfunction as the first stage of atherogenesis. Experiments on endothelial cells isolated from various blood vessels are used to study short-term effects of substances and drugs on the endothelium. One of the effects studied in endothelial cell...
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Study of interactions of antiviral drugs with selected placental transporters
Karbanová, Sára ; Štaud, František (advisor) ; Kacerovský, Marian (referee) ; Mladěnka, Přemysl (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Sára Karbanová, MSc. Supervisor: prof. PharmDr. František Štaud, Ph.D. Consultant: doc. PharmDr. Lukáš Červený, Ph.D. Title of Dissertation Thesis: Study of interactions of antiviral drugs with selected placental transporters The backbone of HIV treatment in pregnant women is the combination antiretroviral therapy which effectively suppresses the viral proliferation in maternal blood circulation. One of drugs in this therapy regimen should be a molecule with high placental transfer to assure the prophylaxis of viral transfer to fetus. There is no approved guideline for pharmacotherapy of pregnant women infected with hepatitis C (HCV), however recent evidence suggests that lowering the maternal viral load could correlate with lower likelihood of HCV transmission to the fetus. To assure and further develop the effective and safe pharmacotherapeutic approaches for treatment of HIV and HCV in pregnancy with respect to fetal safety, it is essential to understand mechanisms of placental transfer of anti(retro)viral drugs. In this Dissertation thesis we focused on molecules derived from nucleosides (anti-HIV abacavir, emtricitabine, zidovudine, tenofovir disoproxil fumarate and anti-HCV...
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