title: In vitro trypanocidal activity of DB745B and other novel arylimidamides against Trypanosoma cruzi.
abstract: OBJECTIVE
  As part of a search for new therapeutic opportunities to treat chagasic patients, in vitro efficacy studies were performed to characterize the activity of five novel arylimidamides (AIAs) against Trypanosoma cruzi.
  
  
  METHODS
  The trypanocidal effect against T. cruzi was evaluated by light microscopy through the determination of IC₅₀ values. Cytotoxicity was determined by MTT assays against mouse cardiomyocytes.
  
  
  RESULTS
  Our data demonstrated the trypanocidal efficacy of these new compounds against bloodstream trypomastigotes and intracellular amastigotes, exhibiting IC₅₀ values ranging from 0.015 to 2.5 and 0.02 to0.2 μM, respectively. One of the compounds, DB745B, was also highly active against a broad panel of isolates, including those naturally resistant to benznidazole. DB745B showed higher in vitro efficacy than the reference drugs used to treat patients (benznidazole IC₅₀= 12.94 μM) and to prevent blood bank infection (gentian violet IC₅₀= 30.6 μM).
  
  
  CONCLUSIONS
  AIAs represent promising new chemical entities against T. cruzi and are also potential trypanocidal agents to prevent transfusion-associated Chagas' disease.
authors.affiliation: Laboratório de Biologia Celular do Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil.
authors.forename: Cristiane França
authors.initials: CF
authors.lastname: Da Silva
authors.forename: Angela
authors.initials: A
authors.lastname: Junqueira
authors.forename: Marli Maria
authors.initials: MM
authors.lastname: Lima
authors.forename: Alvaro José
authors.initials: AJ
authors.lastname: Romanha
authors.forename: Policarpo Ademar
authors.initials: PA
authors.lastname: Sales Junior
authors.forename: Chad E
authors.initials: CE
authors.lastname: Stephens
authors.forename: Phanneth
authors.initials: P
authors.lastname: Som
authors.forename: David W
authors.initials: DW
authors.lastname: Boykin
authors.forename: Maria de Nazaré Correia
authors.initials: Mde N
authors.lastname: Soeiro
mesh_terms: D000578:Amidines / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology* / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008853:Microscopy; D032383:Myocytes, Cardiac / Q000187:drug effects; D021261:Parasitic Sensitivity Tests; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D000578:Amidines; D000981:Antiprotozoal Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue