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.

Autor: Volpato H; Programa de Pós-Graduação em Ciências Biológicas-Biologia Celular e Molecular, Universidade Estadual de Maringá, Maringá, Paraná, Brazil., Desoti VC; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Paraná, Brazil., Valdez RH; Departamento de Farmácia, Instituto Federal do Paraná, Palmas, Paraná, Brazil., Ueda-Nakamura T; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Paraná, Brazil., Silva Sde O; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Paraná, Brazil., Sarragiotto MH; Departamento de Química, Universidade Estadual de Maringá, Maringá, Paraná, Brazil., Nakamura CV; Programa de Pós-Graduação em Ciências Biológicas-Biologia Celular e Molecular, Universidade Estadual de Maringá, Maringá, Paraná, Brazil; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Paraná, Brazil.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2015 Jun 18; Vol. 10 (6), pp. e0130652. Date of Electronic Publication: 2015 Jun 18 (Print Publication: 2015).
DOI: 10.1371/journal.pone.0130652
Abstrakt: 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.
Databáze: MEDLINE
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