Cm-p5, a synthetic antimicrobial peptide shows anti-Trypanosoma cruzi activity

Chagas disease is a neglected disease caused by Trypanosoma cruzi, which affects 6-7 million people worldwide. More than one hundred years after its description, the performance of available drugs for treating the T. cruzi infection remains largely unsatisfactory. Antimicrobial peptides (AMPs) are new alternatives that may have potential as trypanocides. Herein, we assessed Cm-p5, a synthetic peptide with previously shown antimicrobial activity, and 10 derivatives. After screening assays using epimastigote forms of the parasite to test their potential as proliferation inhibitors, Cm-p5 was selected. Cm-p5 showed an EC50 against T. cruzi of 16.9 ± 1.2 μM and a cytotoxicity towards CHO-K1 mammalian cells (CC50) of 124.8 ± 0.1 µM. After further investigation, it was evidenced that part of the epimastigote population underwent necrosis-like cell death, while those that remained alive showed a cell-cycle arrest at the phases G2_M and S_G2. When infected cells were treated, the peptide diminished the release of the infective trypomastigote form, with an EC50 of 25.2 ± 1.4 µM. Furthermore, Cm-p5 inhibited the number of intracellular amastigotes as well as the number of infected cells by 64.3 and 75%, respectively. Taken together, these numbers resulted in a reduction of the infection index by 91.1%. Additionally, we showed that Cm-p5 trypanocidal activity against intracellular amastigotes was attributable to cell membrane damage and cell cycle partial arrest, as described for epimastigotes. Our data suggest that Cm-p5 may be a promising template to design new peptides for the treatment of Chagas disease.