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Chelating Polymers for the Haemochromatosis Treatment
Groborz, Ondřej ; Hrubý, Martin (advisor) ; Kotek, Jan (referee)
5 Chelating Polymers for the Haemochromatosis Treatment Author: Ondřej Groborz Tutor: Mgr. Martin Hrubý, Ph.D., DSc. Advisors: Ing. Kristýna Kolouchová Ing. Pavel Švec Institute of Macromolecular Chemistry, Czech Academy of Sciences Abstract Haemochromatosis is a group of hereditary diseases which are characterised by toxic accumulation of iron in parenchymal organs, leading to organ toxicity and irreversible damage. Currently, there are only a few approved medications for this disease, yet all of them possess severe side effects. Herein, we have proposed a new paradigm for treatment: insoluble polymers with negligible systemic biological availability would form stable complexes with iron ions in the gastrointestinal tract, hence decreasing biological availability of iron. The insolubility of polymers prevents them from being absorbed into the organism in the first place while having no systemic side effects or toxicity. We have prepared polymers with several covalently bound iron-chelating ligands and based on the biological data we selected the most successful chelators for possible future applications. These polymers exhibited negligible resorbability and toxicity, superior in vitro iron chelating activity and their efficacy was proven in an in vivo model. Therefore they could be used as a...
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Interference of reducing agents with the hematoxylin assay for determination of cupric chelation
Zsáková, Emily ; Mladěnka, Přemysl (advisor) ; Vorčáková, Katarína (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Emily Zsáková Supervisor: Assoc. Prof. Přemysl Mladěnka, PharmD., Ph.D. Title of diploma thesis: Interference of reducing agents with the hematoxylin assay for determination of cupric chelation Copper is an essential trace element of living organisms. Disorders of its homeostasis affect various pathological conditions. In excessive amounts, it is toxic due to its ability to form free radicals. Vitamin C, trolox (a water soluble form of vitamin E), glutathione and hydroxylamine possess reducing properties that protect our body from oxidative tissue damage. Oxidized glutathione (GSSG) was also tested for comparison. The object of study was to test the chelating ability of these substances. A simple and fast spectrophotometric method was used. The combination of reducing properties of copper and chelating agents could lead to an improvement in chelation therapy either in heavy metal poisoning, treatment of Wilson's disease, or other diseases. We found that all substances were chelators/copper-chelating agents in vitro in a slightly competitive environment, using hematoxylin as an indicator. However, by using the bathocuproine assays to verify chelating properties, none of the substances...
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Ability of copper chelators to interact with iron and zinc
Hanuščinová, Lucia ; Mladěnka, Přemysl (advisor) ; Čonka, Patrik (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Lucia Hanuščinová Supervisor: Assoc. Prof. Přemysl Mladěnka, PharmDr., PhD. Title of diploma thesis: Ability of copper chelators to interact with iron and zinc Copper plays in the human organism a role of an element with indispensable significance, whose biological influence and effects depend on its quantity. With elevated concentrations in the human body, copper becomes toxic, resulting in pathological conditions. The most well-known diseases is the Wilson's disease, whose treatment consists of oral administration of chelators, i.e. chemical compounds, which are capable of binding copper ions in various proportions and eliminating them from the organism. Chelation therapy is currently the first choice after confirmation of the diagnosis. Chelation toxicity results from several factors, e.g. inhibition of copper dependent enzymes or low selectivity to metals. And precisely the selectivity of chelators is being discussed in this diploma thesis. An ideal chelator should not interact with any of the other physiological ions, that are necessary for the proper functioning of the organism. Five of the most frequently therapeutically or experimentally used substances /trientine, D-penicillamine,...
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Ability of copper chelators to interact with iron and zinc
Hanuščinová, Lucia ; Mladěnka, Přemysl (advisor) ; Čonka, Patrik (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Lucia Hanuščinová Supervisor: Assoc. Prof. Přemysl Mladěnka, PharmDr., PhD. Title of diploma thesis: Ability of copper chelators to interact with iron and zinc Copper plays in the human organism a role of an element with indispensable significance, whose biological influence and effects depend on its quantity. With elevated concentrations in the human body, copper becomes toxic, resulting in pathological conditions. The most well-known diseases is the Wilson's disease, whose treatment consists of oral administration of chelators, i.e. chemical compounds, which are capable of binding copper ions in various proportions and eliminating them from the organism. Chelation therapy is currently the first choice after confirmation of the diagnosis. Chelation toxicity results from several factors, e.g. inhibition of copper dependent enzymes or low selectivity to metals. And precisely the selectivity of chelators is being discussed in this diploma thesis. An ideal chelator should not interact with any of the other physiological ions, that are necessary for the proper functioning of the organism. Five of the most frequently therapeutically or experimentally used substances /trientine, D-penicillamine,...
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The design and synthesis of selective copper(II) chelators
Havlík, Jan ; Kotek, Jan (advisor) ; Holzhauser, Petr (referee)
Title: Design and synthesis of selective copper(II) chelators Author: Jan Havlík Department: Department of Inorganic Chemistry, Faculty of Science Supervisor: assoc. prof. RNDr. Jan Kotek, Ph.D. Supervisor's e-mail address: modrej@natur.cuni.cz The aim of this work was to prepare selective copper(II) chelators. Within the frame of this thesis were synthesized 13 compounds, from which 7 are new. All compounds were fully characterized by NMR spectroscopy and mass spectrometry. Copper(II) complex of synthesized ligand 1,11-bis(methylphosphinic acid)cyclam, (1,11-dipin), was studied in thermodynamic and formation/decomplexation studies. For 1,11-dipin-copper(II) complex were determined values of rate constants and activation parameters. Keywords: selective chelator, copper, cyclam derivatives, macrocyclic ligands, methylphosphonate, methylphosphinate
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