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Apr 15 11 2:09 PM

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In vitro trypanocidal activity of DB745B and other novel arylimidamides against Trypanosoma cruzi

  1. Cristiane França Da Silva1,
  2. Angela Junqueira2,
  3. Marli Maria Lima3,
  4. Alvaro José Romanha4,
  5. Policarpo Ademar Sales Junior4,
  6. Chad E. Stephens5,
  7. Phanneth Som6,
  8. David W. Boykin6 and
  9. Maria de Nazaré Correia Soeiro1,*

+ Author Affiliations

  1. *Corresponding author. Tel: +55-21-25621368; Fax: +55-21-25621432; E-mail: soeiro@ioc.fiocruz.br
  • Received December 15, 2010.
  • Revision requested January 25, 2011.
  • Revision received March 4, 2011.
  • Accepted March 6, 2011.

Abstract

Objectives 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.