title: 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.
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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  These finding suggest that mitochondria are a target of C4, the dysfunction of which can lead to different pathways of cell death.
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas-Biologia Celular e Molecular, Universidade Estadual de Maringá, Maringá, Paraná, Brazil.
authors.forename: Hélito
authors.initials: H
authors.lastname: Volpato
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Paraná, Brazil.
authors.forename: Vânia Cristina
authors.initials: VC
authors.lastname: Desoti
authors.affiliation: Departamento de Farmácia, Instituto Federal do Paraná, Palmas, Paraná, Brazil.
authors.forename: Rodrigo Hinojosa
authors.initials: RH
authors.lastname: Valdez
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Paraná, Brazil.
authors.forename: Tânia
authors.initials: T
authors.lastname: Ueda-Nakamura
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Paraná, Brazil.
authors.forename: Sueli de Oliveira
authors.initials: Sde O
authors.lastname: Silva
authors.affiliation: Departamento de Química, Universidade Estadual de Maringá, Maringá, Paraná, Brazil.
authors.forename: Maria Helena
authors.initials: MH
authors.lastname: Sarragiotto
authors.affiliation: 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.
authors.forename: Celso Vataru
authors.initials: CV
authors.lastname: Nakamura
mesh_terms: D000814:Aniline Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002243:Carbolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D048429:Cell Size / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism*; D010718:Phosphatidylserines / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D026082:Singlet Oxygen / Q000378:metabolism; D014344:Trypanocidal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000814:Aniline Compounds; D002243:Carbolines; C000607383:N-butyl-1-(4-dimethylamino)phenyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxamide; D010718:Phosphatidylserines; D017382:Reactive Oxygen Species; D014344:Trypanocidal Agents; D026082:Singlet Oxygen