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

Objectives: As part of a search for newtherapeutic 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. cruziwas 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 to 0.2 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.