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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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Search of effective cobalt chelators - 8-hydroxyquinolines
Pelnářová, Karolína ; Mladěnka, Přemysl (advisor) ; Carazo Fernández, Alejandro (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Karolína Pelnářová Supervisor: Prof. Přemysl Mladěnka, PharmD., Ph.D. Consultant: Václav Tvrdý, MSc.; Marcel Hrubša, MSc. Title of diploma thesis: Searching of effective cobalt chelators - 8-hydroxyquinolines Cobalt is one of the essential trace elements present in the human body. It forms a part of the organometallic complex of vitamin B12, which is essential for many physiological functions. Both overload and lack of cobalt in the body is associated with pathological conditions. Manifestations of deficiency can lead up to pernicious anemia or hypofunction of the thyroid gland. Cobalt intoxication can occur in an industrial environment, such as by cobalt metal dust during heavy metal processing, or by its release due to corrosion from orthopedic prostheses. Systemic toxicity is manifested by a number of endocrine, cardiovascular and neurological symptoms. The main aim of this diploma thesis was to find effective chelators of cobalt from the group of substances derived from 8-hydroxyquinoline. In vitro spectrophotometric measurement was used to determine the degree of chelation. The effect of chelation was also monitored ex vivo in rat erythrocytes. All tested chelators - 8-hydroxyquinoline,...
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Comparasion of interaction of cyanidin and cyanidin-3-glucoside with copper and iron
Gavurová, Lucie ; Mladěnka, Přemysl (advisor) ; Smutná, Lucie (referee)
Iron and copper are trace elements involved in many essential processes in the human body. Copper plays an important role in human metabolism, primarily as a cofactor of many metalloenzymes, like superoxide dismutase and ceruloplasmin. Copper is also essential for iron homeostasis. Iron is incorporated into many biomolecules like heme or enzymes, and is hence vital for cellular processes like oxygen transport, energy production and DNA synthesis. In biological systems, copper is present in both the oxidised form of cupric (Cu2+ ), and the reduced form as cuprous ion (Cu+ ). Iron as well exists in two stable oxidation states as ferrous (Fe2+ ) or ferric ion (Fe3+ ). Due to their strong redox potential, both elements can be potentially toxic to the body. Iron accumulates in vital organs such as the liver, heart and kidneys. Wilson's disease is an example of copper overload disease resulting from pathogenic mutations in gene ATP7B. The iron excess in the body is usually associated with iron overloading conditions, such as hereditary hemochromatosis or repeated treatments with blood transfusions (e.g. in thalassemia). In such cases, drugs with chelating or reducing effect are convenient for clinical use. The aim of this thesis was to compare the interaction of the chelating and reducing efficacy of two...
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Optimization of PEI based LbL capsules with pDNA
Ondrašáková, Petra ; Mladěnka, Přemysl (advisor) ; Hofman, Jakub (referee)
Ab rac Charle Uni er i Fac l of Pharmac in Hradec Kr lo Depar men of Pharmacolog and To icolog S den : Pe ra Ondra ko , MSc. S per i or: A oc. Prof. P em l Mlad nka, Pharm.D., Ph.D. Co- per i or: Dr. Haider Sami, Uni er i of Vienna, Di i ion of Clinical Pharmac and Diagno ic Ti le of rigoro he i : Op imi a ion of PEI ba e LbL cap le i h pDNA In hi he i , e foc ed on he de elopmen of pol e h lenimine (PEI) ba ed non- iral cap le , hich ill en er n cle of he cancer cell and lead o he e pre ion of he lacking pro ein, hich ca e di ea e. A fir , PEI ba ed la er-b -la er (LbL) pol mer cap le ere formed. PEI ha man ad an age - i ha pro onable amine , good abili and ran fec ion efficienc . When forming he cap le, I follo ed p on m diploma he i and con in ed o op imi e he mo i able combina ion of pol mer , ha ere la ered on he CaCO3core. The aim a o ob ain a biodegradable cap le and hen o incorpora e pla mid DNA (pDNA) herein. Fl ore cen l labelled PEI a ed a he la la er o i ali e par icle in fl ore cen micro cope. Then a canning elec ron micro cope (SEM) a ed o ob er e cap le in more de ail . UV-VIS and Dapi aining ere ed o ee he her here i pDNA bo nd in cap le . Ne ep ere i i cell e perimen on mo e mammar cancer cell - c o o ici and cell lar in ake. Vi ali a ion a pro ided i h fl ore cen micro cop . 2 pe of...
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The impact of synthetic chelators from the group of 4-acylpyrazole-5-ones on alcohol dehydrogenase
Sobolová, Zuzana ; Mladěnka, Přemysl (advisor) ; Jirkovský, Eduard (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Zuzana Sobolová Supervisor: Prof. Přemysl Mladěnka, Pharm.D., Ph.D. Consultant: Marcel Hrubša, MS.c. Title of diploma thesis: The impact of synthetic chelators from the group of 4-acylpyrazole-5-ones on alcohol dehydrogenase Inhibitors of alcohol dehydrogenase play a key role in the treatment of poisoning caused by methanol, ethanol, ethylene glycol, and their toxic metabolites. Such treatment can therefore be considered as life-saving. In clinical practice, a single substance, fomepizole, is used. This thesis is aimed at investigation of the effect of eleven experimental chelators from the 4- acylpyrazol-5-ones group on equine and yeast alcohol dehydrogenases, and the possible definition of structural features that would be the most suitable for interaction with this enzyme. Due to the ability of these substances to chelate zinc ions, it is believed that they could inhibit an enzyme that has a zinc molecule in the structure. The measurement itself is based on principle of increase in absorbance during the enzymatic reaction, which is caused by the formation of NADH. This measurement is relatively simple, efficient and, due to used kinetic method, also less susceptible to be affected by...
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Interaction of chalcones with transition metals II.
Šulcová, Martina ; Macáková, Kateřina (advisor) ; Mladěnka, Přemysl (referee)
Charles University in Prague Faculty of Phramacy in Hradec Králové Department of Pharmaceutical Botany Candidate: Martina Šulcová Supervisor: Assoc. Prof. Ing. Kateřina Macáková, Ph.D. Title of the diploma thesis: Interaction of chalcones with transition metals II. Copper is one of the essencial elements in human body which is involved in the functioning of many enzymes and metabolic pathways. Although it appears in trace amounts in the body, its functions are irreplaceable. However, the ion level must be kept in balance by the various mechanisms of the body. If there is an excess or deficiency of copper in the body, this condition can lead to the development of health issues. Chalcones are substances belonging to the group of flavonoids. Their polyphenolic structure does not have a closed ring C. Studies describe their anticancer, anti-inflammatory, antiviral, antidiabetic, antibacterial, antioxidant, immunosuppressive and other properties. Chosen substances in the group of dihydrochalcones (naringin dihydrochalcone, neohesperidin dihydrochalcone, phloretin, phlorizin) and chalcones (isoliquiritigenin, licochalcone A) were tested for their chelation and reduction activity of the copper ions in this diploma thesis. The activity was measured at different pH environments (7.5; 6.8; 5.5 and 4.5) and...
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Preparation of a method for detection of the extent of chelation of calcium and magnesium ions
Konečný, Lukáš ; Mladěnka, Přemysl (advisor) ; Jáč, Pavel (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Lukáš Konečný Supervisor: prof. Přemysl Mladěnka, Pharm.D., Ph.D. Title of Thesis: Preparation of a method for detection of the extent of chelation of calcium and magnesium ions Calcium and magnesium are biogenic elements belonging to the second group of the periodic table. Calcium is the fifth most abundant element in the human body. In addition to its important role in bone homeostasis, calcium is involved in other processes such as blood clotting, muscle contraction and regulation of nerve excitability Magnesium is the cofactor of many enzymatic reactions essential for a row of physiological functions. The aim of this work was to propose a novel screening method for determination of the degree of calcium and magnesium chelation. In the first step the UV-vis spectra of the selected indicator o-cresolphthalein complexone and its complexes with calcium and magnesium were measured. This was followed by verification of the linearity and the determination of the sensitivity of the method. Concurrently the stability of the indicator and its complexes with both ions was measured. In the last step, the suitability of the method was verified on a standard chelator ethylenediaminetetraacetic acid...
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Search of effective cobalt chelators - 8-hydroxyquinolines
Pelnářová, Karolína ; Mladěnka, Přemysl (advisor) ; Carazo Fernández, Alejandro (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Karolína Pelnářová Supervisor: Prof. Přemysl Mladěnka, PharmD., Ph.D. Consultant: Václav Tvrdý, MSc.; Marcel Hrubša, MSc. Title of diploma thesis: Searching of effective cobalt chelators - 8-hydroxyquinolines Cobalt is one of the essential trace elements present in the human body. It forms a part of the organometallic complex of vitamin B12, which is essential for many physiological functions. Both overload and lack of cobalt in the body is associated with pathological conditions. Manifestations of deficiency can lead up to pernicious anemia or hypofunction of the thyroid gland. Cobalt intoxication can occur in an industrial environment, such as by cobalt metal dust during heavy metal processing, or by its release due to corrosion from orthopedic prostheses. Systemic toxicity is manifested by a number of endocrine, cardiovascular and neurological symptoms. The main aim of this diploma thesis was to find effective chelators of cobalt from the group of substances derived from 8-hydroxyquinoline. In vitro spectrophotometric measurement was used to determine the degree of chelation. The effect of chelation was also monitored ex vivo in rat erythrocytes. All tested chelators - 8-hydroxyquinoline,...
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Screening of New Iron - and Copper - Chelating Substances - in vivo and in vitro Studies
Říha, Michal ; Mladěnka, Přemysl (advisor) ; Patočka, Jiří (referee) ; Tůmová, Lenka (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Michal Říha, MSc. First Supervisor: Assoc. Prof. Přemysl Mladěnka, Ph.D. Second Supervisor: Prof. Radomír Hrdina, M.D., Ph.D. Title of Doctoral Thesis: Screening of new iron- and copper-chelating substances - in vivo and in vitro studies Iron and copper are essential trace elements which play a role in a series of physiological processes in human organism. Homeostasis of these transition metals is meticulously regulated since free or loosely bound iron and copper can catalyse the production of free radicals. Hereditary hemochromatosis, transfusion hemosiderosis and Wilson's disease are associated with absolute iron and copper overload in the organism. Transition metal chelators have crucial significance for the treatment of these states. There are several other diseases with documented involvement of iron and/or copper in their pathophysiology. Examples are primarily neurodegenerative diseases, cardio- vascular diseases, tumours and diabetes mellitus. Various chelating compounds are examined in these possible indications. The aim of this doctoral thesis was to perform a screening of iron- and copper- chelating substances and to study their properties in detail using in vitro and...
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Copper-chelating properties of isoflavonoids
Horňasová, Veronika ; Mladěnka, Přemysl (advisor) ; Spilková, Jiřina (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Veronika Horňasová Supervisor: Assoc. Prof. Přemysl Mladěnka, Ph.D. Title of diploma thesis: Copper-chelating properties of isoflavonoids Copper is an essential trace element that plays a crucial role in our organism. It is involved in many physiological processes. On the other hand, free copper may be toxic for the organism and therefore copper homeostasis must be carefully controlled. Copper chelators represent a promising component of therapeutic strategies not only in absolute but also in relative (local) excess of copper. Especially substances which are expected to have a lower risk for side effects, such as isoflavones, may be beneficial in the treatment of Wilson's disease as well as neurodegenerative diseases or cancer. Isoflavones belong to one of the subclasses of flavonoids. Their biological effects are quite large - anti-inflammatory, antioxidant, cardio- and neuroprotective and anti-tumor. In this diploma thesis chelating properties of a group of ten isoflavones were tested by two indicators - hematoxylin and bathocuproin. In order to determine the chelating properties, a spectrophotometric measurement was used. It is a precise and rapid method. From the tested compounds,...
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