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Publication type: Journal Article
Document type: Full Paper

Year: 2020

Author(s): Geroldinger, G; Tonner, M; Quirgst, J; Walter, M; De Sarkar, S; Machín, L; Monzote, L; Stolze, K; Catharina Duvigneau, J; Staniek, K; Chatterjee, M; Gille, L

Title: Activation of Artemisinin and Heme Degradation in Leishmania tarentolae Promastigotes: A Possible Link.

Source: Biochem Pharmacol. 2020; 173:113737



Authors Vetmeduni Vienna:

Duvigneau Catharina
Geroldinger Gerald
Gille Lars
Staniek Katrin
Stolze Klaus
Tonner Matthias Stefan

Vetmed Research Units
Institute for Medical Biochemistry
Institute of Animal Nutrition and Functional Plant Compounds
Institute of Pharmacology and Toxicology


Project(s): Triggers and Targets of Ascaridole Action in Leishmania


Abstract:
Endoperoxides (EPs) appear to be promising drug candidates against protozoal diseases, including malaria and leishmaniasis. Previous studies have shown that these drugs need an intracellular activation to exert their pharmacological potential. The efficiency of these drugs is linked to the extensive iron demand of these intracellular protozoal parasites. An essential step of the activation mechanism of these drugs is the formation of radicals in Leishmania. Iron is a known trigger for intracellular radical formation. However, the activation of EPs by low molecular iron or by heme iron may strongly depend on the structure of the EPs themselves. In this study, we focused on the activation of artemisinin (Art) in Leishmania tarentolae promastigotes (LtP) in comparison to reference compounds. Viability assays in different media in the presence of different iron sources (hemin/fetal calf serum) showed that IC


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