Inhibitorische Effekte von 1-Hydroxychinolonen auf Toxoplasma gondii

Inhibitory effects of 1-hydroxyquinolones on Toxoplasma gondii

von Christian Platte
Dissertation
Datum der mündl. Prüfung:2023-11-14
Erschienen:2023-11-09
Betreuer:Prof. Dr. Uwe Groß
Gutachter:Prof. Dr. Uwe Groß
Gutachter:PD Dr. Alexander Hahn
Gutachter:Prof. Dr. Ralf Dressel
Zum Verlinken/Zitieren: http://dx.doi.org/10.53846/goediss-10155

 

 

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Zusammenfassung

Englisch

Within the mitochondria of Toxoplasma gondii, 1-hydroxyquinolones were identified as affine inhibitors of the alternative NADH-dehydrogenase at the first complex of the respiratory chain. Another target structure of the compound was confirmed to be the dihydroorotate-dehydrogenase, an enzyme in pyrimidine biosynthesis. The mode of action of the substances was also examined by the use of two deletion-mutants and the length of the alkyl side chain of the 1-hydroxyquinolones was identified as a structurally important and functional aspect. As a result, hydroxyquinolones exerted a parasitostatic effect on Toxoplasma gondii in long-term experiments and the parasite almost stopped its dividing activity. Furthermore, under the influence of hydroxyquinolones, a significant decrease in ATP content and a disruption of the mitochondrial membrane potential (ΔΨm) were detected in Toxoplasma gondii, which illustrated the influence of the compounds on the metabolism of the parasite.
Keywords: toxoplasma gondii; hydroxyquinolones; respiratory chain; growth inhibition; Inhibitory effect; mitochondrial membrane potential; atp content; parasite; 1-hydroxyquinolones
Schlagwörter: Toxoplasma gondii; Atmungskette; Hydroxychinolon; 1-Hydroxychinolon; Wachstumshemmung; ATP-Gehalt; Membranpotential
 
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