Abstract
Due to well‐know efficacy of aromatic diamidines and analogues upon a wide range of pathogens including trypanosomatids such as T. cruzi, which still displays a unsatisfactory chemotherapy, our aim was to investigate the biological activity of DB766, a reversed amidine (RA), against bloodstream forms (BT) and amastigotes of T. cruzi (Y strain) in vitro. DB766 displayed an excellent trypanocidal effect towards BT incubated at 37ºC for 24h (IC50 0.05μM). Addition of blood constituents did not impair the drug effect (IC50 0.16μM), measured by incubation at 4ºC/24h. Mammalian cells evaluated by CK‐MB and MTT assays showed the lack of drug toxicity upon uninfected cardiomyocytes (CM) and peritoneal macrophages incubated at doses up to 10.6μM. T. cruzi‐infected CM treated with non‐toxic doses (10.6‐0.04μM) of DB766 resulted in a potent dose and time‐dependent effect (IC50 24h 0.03μM), leading to a considerable reduction in both the percentage of infected cells as well as in the mean number of parasites per infected cells. Fluorescent approaches showed that RA impaired the myofibrils breakdown noticed in T. cruzi‐infected CM not submitted to drug incubation. Our data demonstrate the excellent effect of DB766 against T. cruzi, which merits further in vivo studies currently underway.
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