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Effect of lipophilic cation on the toxicity of phosphonium salts in parasitic protists
Čadková, Aneta ; Mach, Jan (advisor) ; Trnka, Jan (referee)
The mitochondrion is an essential organelle responsible for energy metabolism and maintaining cellular homeostasis. Disruption of their function can have serious consequences for the entire cell and organism. Given their key role in the organism, they become an attractive target for drugs. In this thesis, we examine the impact and significance of phosphonium salts as potential mitochondrial-targeted therapeutics. The investigated compounds have modified anchors based on the commonly used triphenylphosphonium cation (TPP+ ). These substances have the ability to permeate the phospholipid bilayer and accumulate on the inner mitochondrial membrane. Our research focuses on selected model organisms of the class Kinetoplastida and opportunistic pathogenic fungi. These pathogenic organisms are responsible for severe infectious diseases in humans. Our aim is to compare the effectiveness of phosphonium salts with different anchor modifications against these organisms and attempt to elucidate their mechanism of action. We have found that the modified salts are capable of inhibiting the growth of parasitic protists at nM concentrations, affecting mitochondrial respiration, membrane potential, and mitochondrial integrity. However, there is no increase in the level of oxygen radicals. We are assuming that the...
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Current options of treatment for parasitic kinetoplastids
Čadková, Aneta ; Mach, Jan (advisor) ; Richterová, Lenka (referee)
Chagas disease, sleeping sickness and leishmaniasis are diseases occurring mainly in developing areas of Africa, America and Asia. They are caused by parasitic kinetoplastids from the genus Trypanosoma and Leishmania. These protozoans undergo morphologic transformations during their development leading to changes of their properties. They are characterized by complex mechanisms that allow them to evade the host's immunity. At the same time, because of these mechanisms and selection pressures, they are able to subsequently develop resistance to used drugs. The diseases caused by protozoa are classified as "neglected tropical diseases". The research and development of drugs against them is heavily underfunded. Currently used drugs are expensive, have a number of side effects, and due to lack of usage regulation develop resistance. The work first generally presents human parasites of the class Kinetoplastida. It further describes the treatment of diseases caused by the characterized species and focuses on a summary of currently used drugs, their mechanism, resistance and potential new drugs in clinical phases. Key words: kinetoplastids, Trypanosoma, Leishmania, treatment, disease, mechanism of action, resistance, nitroreductase
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Geometric exercises in paper folding
ČADKOVÁ, Aneta
The aim of the bachelor thesis Geometric exercises in paper folding is to show that paper folding is not only suitable for mathematical reasoning of structures, but also because of the use of student's manual skills, and for applications in practice as well. Based on Huzita's axioms, we can realize that folding the paper exceeds the possibilities of Euclidean constructions with a ruler and compass. Through paper folding we can divide any angle into three equal parts (i.e. angle trisection) or construct a regular heptagon - constructions which cannot be done classically, using a ruler and compass.
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