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Selective screening of antiparasitic substances
Wernerová, Klára ; Mach, Jan (advisor) ; Kovářová, Julie (referee)
The mitochondrion is the key organelle of the cell. It is involved in energy metabolism, the Krebs cycle, the respiratory chain, and the formation of Fe-S clusters, which form the structure of many proteins. Therefore, disruption of the mitochondria is usually fatal to the cell, especially if it contains only one mitochondrion, as is the case in Trypanosoma brucei brucei. The T. b. brucei parasite has become the primary model organism for our study because its basic biochemical processes are already well described, including mitochondrial metabolism, and it is also easy to cultivate in the laboratory. Other model organisms we used in this study were Leishmania mexicana, Cryptococcus neoformans and Candida albicans. All these organisms are causative agents of serious diseases, and although there are drugs against them, new drugs need to be developed due to the frequent emergence of resistances. Mitochondria-targeting drugs are promising for the pharmaceutical industry. In this work, we investigate the efficacy of compounds whose structure is composed of a mitochondrial phosphonium anchor linked to a carbon chain. These substances are capable of incorporation into the mitochondrial membranes. The work not only focuses on comparing the potency of the tested substances in selected model organisms, but...
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