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BACKGROUND   Chagas disease, which is caused by the protozoan  Trypanosoma cruzi , is endemic to Latin America and mainly affects low-income populations. Chemotherapy is based on two nitrocompounds, but their reduced efficacy encourages the continuous search for alternative drugs. Our group has characterised the trypanocidal effect of naphthoquinones and their derivatives, with naphthoimidazoles derived from β-lapachone (N1, N2 and N3) being the most active  in vitro .    OBJECTIVES   In the present work, the effects of N1, N2 and N3 on acutely infected mice were investigated.    METHODS    in vivo  activity of the compounds was assessed by parasitological, biochemical, histopathological, immunophenotypical, electrocardiographic (ECG) and behavioral analyses.    FINDINGS   Naphthoimidazoles led to a decrease in parasitaemia (8 dpi) by reducing the number of bloodstream trypomastigotes by 25-50% but not by reducing mortality. N1 protected mice from heart injury (15 dpi) by decreasing inflammation. Bradycardia was also partially reversed after treatment with N1 and N2. Furthermore, the three compounds did not reverse hepatic and renal lesions or promote the improvement of other evaluated parameters.    MAIN CONCLUSION   N1 showed moderate trypanocidal and promising immunomodulatory activities, and its use in combination with benznidazole and/or anti-arrhythmic drugs as well as the efficacy of its alternative formulations must be investigated in the near future.

Antiparasitic and anti-inflammatory activities of ß-lapachone-derived naphthoimidazoles in experimental acute Trypanosoma cruzi infection