Mitochondrial Dysfunction Induced by N-Butyl-1-(4-Dimethylamino)Phenyl-1,2,3,4-Tetrahydro-β-Carboline-3-Carboxamide Is Required for Cell Death of Trypanosoma cruzi.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 26086449.
- Also identified by DOI 10.1371/journal.pone.0130652 and PMC identifier 4472351.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
BACKGROUND: Chagas' disease is caused by the protozoan Trypanosoma cruzi and affects thousands of people worldwide. The available treatments are unsatisfactory, and new drugs must be developed. Our group recently reported the trypanocidal activity of the synthetic compound N-butyl-1-(4-dimethylamino)phenyl-1,2,3,4-tetrahydro-β-carboline-3-carboxamide (C4), but the mechanism of action of this compound was unclear. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the mechanism of action of C4 against epimastigote and trypomastigote forms of T. cruzi. The results showed alterations in mitochondrial membrane potential, alterations in cell membrane integrity, an increase in the formation of reactive oxygen species, phosphatidylserine exposure, a reduction of cell volume, DNA fragmentation, and the formation of lipid inclusions. CONCLUSION/SIGNIFICANCE: These finding suggest that mitochondria are a target of C4, the dysfunction of which can lead to different pathways of cell death.
Medical subject headings
- Aniline Compounds
- Carbolines
- Mitochondria
- Trypanocidal Agents
- Trypanosoma cruzi