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Interaction of 7,8-dihydroxyflavone with physiological metals
Streďanská, Aneta ; Mladěnka, Přemysl (advisor) ; Červený, Lukáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Aneta Streďanská Supervisor: prof. Přemysl Mladěnka, Pharm.D., PhD. Consultant: Zuzana Lomozová, Pharm.D., PhD. Title of thesis: Interactions of 7,8-dihydroxyflavone with physiological metals 7,8-dihydroxyflavone belongs to the phenolic substances collectively referred to as flavonoids. Flavonoids are bioactive components abundantly distributed in the daily diet with the ability to modulate health and disease through miscellaneous mechanisms including their antioxidant activity. However, they can also exhibit prooxidative effects under certain conditions. Due to this fact, which is related to individual factors, i.e. presence of various substitutions on the flavonoid come, it is therefore essential to understand the redox behavior based on the relationship between structure and effect and to understand their physiological, pharmacological and thus also potential toxic properties. The interaction with physiological metals is determined by the structure of the molecule through the dihydroxy moiety in positions 7 and 8. These mentioned metals are essential for many biochemical processes in biological systems. Their homeostasis is strictly regulated in the human body and disruption of this...
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Interactions of essential amino acids with iron ions
Nadějová, Jana ; Karlíčková, Jana (advisor) ; Siatka, Tomáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacognosy and Pharmaceutical Botany Candidate: Jana Nadějová Supervisor: PharmDr. Jana Karlíčková, Ph.D. Title of Thesis: Interaction of essential amino acids with iron ions Iron is an important trace element that is needed for the proper functioning of the body. Lack of iron, as well as an excess of iron, can lead to pathological conditions, so it is necessary to control the level of iron in the blood and in case of overloading the body with iron, its chelation can be considered a possible therapeutic tool. Chelators for these therapeutic purposes should be the body's own substance. Amino acids are therefore ideal candidates for the regulation of iron homeostasis in the body, so this thesis focuses on some of them. The individual amino acids are linked by a peptide bond to form proteins. Proteinogenic amino acids are divided into essential, which must be ingested through food, and nonessential, which the body can create on its own. The aim of this study was to compare the iron-chelating and iron-reducing activity of the essential amino acids L-histidine, L-methionine, and the nonessential amino acids L- cysteine, its dimer L-cystine, L-aspartic and L-glutamic acid. The research also included a substance derived from...
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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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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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Searching for natural cobalt chelators
Kadlecová, Kateřina ; Karlíčková, Jana (advisor) ; Carazo Fernández, Alejandro (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacognosy and Pharmaceutical Botany Student: Kateřina Kadlecová Supervisor: PharmDr. Jana Karlíčková, Ph.D. Title of diploma: Searching for natural cobalt chelators Cobalt, as a trace element, is mostly found in the human body as the central atom of vitamin B12. Its deficiency is manifested by psychological impairment, memory loss, dementia or megaloblastic anemia. In excess amount, it is toxic to the body, which has been most described in patients with MoM hip replacement surgery. Cobalt causes damage to surrounding tissue until it is destroyed, or also cardiotoxicity, thyroid hypofunction, memory and hearing loss. Flavonoids are natural polyphenolic compounds with the ability to bind metals, scavenge free radicals and hence protect against oxidative stress. The aim of the work was to determine the cobalt chelating activity of a row of flavonoids using spectrofotometric measurements in vitro at 4 pathophysiologically relevant pH conditions (pH 4.5, 5.5, 6.8 and 7.5). Of the test substances, only 3-hydroxyflavon and baicalein showed chelation activity. 3-hydroxyflavon in a 1:1 ratio achieved 100 % chelation at pH 7.5 and about 60 % at pH 6.8. Baicalein was reactive at pH 7.5 and 6.8, when at 10:1 it was able to bind about 50...
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Search for an efficient cobalt chelator
Nosková, Karolína ; Mladěnka, Přemysl (advisor) ; Smutný, Tomáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Karolína Nosková Supervisor: prof. Přemysl Mladěnka, PharmD., Ph.D. Consultant: Monika Moravcová, MSc. Title of diploma thesis: Search for an efficient cobalt chelator Cobalt, as part of vitamin B12, is an essential trace element for human organism. However, long-term exposure to high doses leads to toxicity. Chronic cobalt intoxication is currently most commonly observed after the implantation of cobalt-containing prostheses, which in some cases do not work properly and cobalt is released from them by mechanical friction or corrosion. That not only leads to a local reaction, but cobalt ions also enter the blood and lymphatic circulation and thus cause a systemic reaction. The intoxication is then manifested by neurological, cardiovascular and endocrine symptoms, which can lead to irreversible changes or even to the death. However, a chelator that would be able to effectively and selectively bind cobalt and thus effectively treat intoxication is not available in clinical practice. The aim of this thesis was a search for an efficient cobalt chelator among known metal chelators. Chelation was measured in vitro by a method based on spectrophotometric detection of unchelated cobalt ions at...
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Interactions of reduced and oxidized glutathione with copper, iron and zinc
Júnová, Ingrid ; Karlíčková, Jana (advisor) ; Jenčo, Jaroslav (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Botany Candidate: Ingrid Salanciová Supervisor: PharmDr. Jana Karlíčková, Ph.D. Title of Thesis: Interactions of reduced and oxidized glutathione with copper, iron and zinc Copper (Cu), iron (Fe) and zinc (Zn) are important trace elements that are necessary for proper function of the body. Excess but also the lack of these metals may lead to pathological conditions. Glutathione is the main antioxidant in the human body so it is expected to protect the organism against concequences of metal excess. Glutathione occurs in the reduced (GSH) and oxidized state as glutathione disulfide (GSSG) in the organism, both states forming an important redox system. On the other hand, glutathione can reduce these metals so that could participate in the formation of free radicals (metal based Fenton reaction). In this diploma thesis, was tested the ability of reduced and oxidized glutathione to interact with Fe, Cu and Zn in various (patho) physiological pH conditions was tested by using in vitro spectrophotometric competitive methods. Interactions include not only the chelation of Cu, Fe and Zn ions, but also their reductive activity toward Cu2+ and Fe3+ cations. Hematoxylin, bathocuproinedisulfonic acid disodium salt, ferrozine...
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Searching for natural cobalt chelators
Kadlecová, Kateřina ; Karlíčková, Jana (advisor) ; Carazo Fernández, Alejandro (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacognosy and Pharmaceutical Botany Student: Kateřina Kadlecová Supervisor: PharmDr. Jana Karlíčková, Ph.D. Title of diploma: Searching for natural cobalt chelators Cobalt, as a trace element, is mostly found in the human body as the central atom of vitamin B12. Its deficiency is manifested by psychological impairment, memory loss, dementia or megaloblastic anemia. In excess amount, it is toxic to the body, which has been most described in patients with MoM hip replacement surgery. Cobalt causes damage to surrounding tissue until it is destroyed, or also cardiotoxicity, thyroid hypofunction, memory and hearing loss. Flavonoids are natural polyphenolic compounds with the ability to bind metals, scavenge free radicals and hence protect against oxidative stress. The aim of the work was to determine the cobalt chelating activity of a row of flavonoids using spectrofotometric measurements in vitro at 4 pathophysiologically relevant pH conditions (pH 4.5, 5.5, 6.8 and 7.5). Of the test substances, only 3-hydroxyflavon and baicalein showed chelation activity. 3-hydroxyflavon in a 1:1 ratio achieved 100 % chelation at pH 7.5 and about 60 % at pH 6.8. Baicalein was reactive at pH 7.5 and 6.8, when at 10:1 it was able to bind about 50...
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Interactions of essential amino acids with iron ions
Nadějová, Jana ; Karlíčková, Jana (advisor) ; Siatka, Tomáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacognosy and Pharmaceutical Botany Candidate: Jana Nadějová Supervisor: PharmDr. Jana Karlíčková, Ph.D. Title of Thesis: Interaction of essential amino acids with iron ions Iron is an important trace element that is needed for the proper functioning of the body. Lack of iron, as well as an excess of iron, can lead to pathological conditions, so it is necessary to control the level of iron in the blood and in case of overloading the body with iron, its chelation can be considered a possible therapeutic tool. Chelators for these therapeutic purposes should be the body's own substance. Amino acids are therefore ideal candidates for the regulation of iron homeostasis in the body, so this thesis focuses on some of them. The individual amino acids are linked by a peptide bond to form proteins. Proteinogenic amino acids are divided into essential, which must be ingested through food, and nonessential, which the body can create on its own. The aim of this study was to compare the iron-chelating and iron-reducing activity of the essential amino acids L-histidine, L-methionine, and the nonessential amino acids L- cysteine, its dimer L-cystine, L-aspartic and L-glutamic acid. The research also included a substance derived from...
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Search for an efficient cobalt chelator
Nosková, Karolína ; Mladěnka, Přemysl (advisor) ; Smutný, Tomáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Karolína Nosková Supervisor: prof. Přemysl Mladěnka, PharmD., Ph.D. Consultant: Monika Moravcová, MSc. Title of diploma thesis: Search for an efficient cobalt chelator Cobalt, as part of vitamin B12, is an essential trace element for human organism. However, long-term exposure to high doses leads to toxicity. Chronic cobalt intoxication is currently most commonly observed after the implantation of cobalt-containing prostheses, which in some cases do not work properly and cobalt is released from them by mechanical friction or corrosion. That not only leads to a local reaction, but cobalt ions also enter the blood and lymphatic circulation and thus cause a systemic reaction. The intoxication is then manifested by neurological, cardiovascular and endocrine symptoms, which can lead to irreversible changes or even to the death. However, a chelator that would be able to effectively and selectively bind cobalt and thus effectively treat intoxication is not available in clinical practice. The aim of this thesis was a search for an efficient cobalt chelator among known metal chelators. Chelation was measured in vitro by a method based on spectrophotometric detection of unchelated cobalt ions at...
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