The crude
venom of the giant ant Dinoponera quadriceps is a cocktail of
polypeptides and organic compounds that shows
antiparasitic effects against Trypanosoma cruzi, the causative agent of
Chagas disease. In order to investigate the
venom-derived components responsible for such antitrypanosomal activity, four dinoponeratoxins (DnTxs) were identified, namely M-PONTX-Dq3a, -Dq3b, -Dq3c and -Dq4e, that are diverse in size, net charge, hydrophobicity and propensity to interact with eukaryote cell membranes. These
peptides were tested against epimastigote, trypomastigote and amastigote forms of
benznidazole (Bz)-resistant Y strain of T. cruzi and in mammalian host cells. The M-PONTX-Dq3a and -Dq4e inhibited all developmental forms of T. cruzi, including amastigotes, the responsible form for the maintenance of
infection on chronic phase of the disease. The M-PONTX-Dq3a showed the highest selectivity index (SI) (80) and caused morphological alterations in T. cruzi, as observed by scanning electron microscopy (SEM), and induced cell death through
necrosis, as seen by multiparametric flow cytometry analysis with specific
biochemical markers. Altogether, the D. quadriceps
venom appears as a source for the prospection of trypanocidal
peptides and the M-PONTX-Dq3a arises as a candidate among the dinoponeratoxin-related
peptides in the development of compounds against
Chagas disease.