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Biomolecules ; 9(9)2019 09 12.
Article in English | MEDLINE | ID: mdl-31547423

ABSTRACT

Trypanosoma cruzi, which causes Chagas disease, is a significant health threat in many countries and affects millions of people. Given the magnitude of this disease, a broader understanding of trypanocidal mechanisms is needed to prevent and treat infection. Natural endoperoxides, such as ergosterol peroxide, have been shown to be toxic to parasites without causing harm to human cells or tissues. Although prior studies have demonstrated the trypanocidal activity of ergosterol peroxide, the cellular and molecular mechanisms remain unknown. The results of this study indicate that a free-radical reaction occurs in T. cruzi following ergosterol peroxide exposure, leading to cell death. Using a combination of biochemical, microscopic and in silico experimental approaches, we have identified, for the first time, the cellular and molecular cytotoxic mechanism of an ergosterol peroxide obtained from Pleurotus ostreatus (Jacq) P. Kumm. f. sp. Florida.


Subject(s)
Cytochrome P-450 Enzyme System/metabolism , Ergosterol/analogs & derivatives , Pleurotus/chemistry , Trypanosoma cruzi/drug effects , Cell Membrane/drug effects , Cell Membrane/metabolism , Crystallography, X-Ray , Cytochrome P-450 Enzyme System/chemistry , Cytoplasm/drug effects , Cytoplasm/metabolism , Ergosterol/chemistry , Ergosterol/pharmacology , Models, Molecular , Molecular Docking Simulation , Molecular Structure , Trypanosoma cruzi/metabolism
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