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

J Antimicrob Chemother. 2011 Jun;66(6):1295-7. doi: 10.1093/jac/dkr140. Epub 2011 Apr 8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amidines / pharmacology*
  • Amidines / toxicity
  • Animals
  • Antiprotozoal Agents / pharmacology*
  • Antiprotozoal Agents / toxicity
  • Cell Survival / drug effects
  • Cells, Cultured
  • Humans
  • Inhibitory Concentration 50
  • Mice
  • Microscopy
  • Myocytes, Cardiac / drug effects
  • Parasitic Sensitivity Tests
  • Tetrazolium Salts / metabolism
  • Thiazoles / metabolism
  • Trypanosoma cruzi / drug effects*

Substances

  • Amidines
  • Antiprotozoal Agents
  • Tetrazolium Salts
  • Thiazoles
  • thiazolyl blue