# Ruthenium Complexes Containing Thiobenzamide Act as Potent and Selective Anti-Trypanosoma cruzi Agents through Apoptotic Cell Death

## TL;DR

This study identifies a new ruthenium-based compound that effectively kills the parasite causing Chagas disease by inducing cell death.

## Contribution

The study introduces FOR0212A, a novel ruthenium complex with potent and selective anti-Trypanosoma cruzi activity.

## Key findings

- FOR0212A showed strong trypanocidal activity with low IC50 values against both trypomastigotes and amastigotes.
- The compound induced apoptosis-like cell death, as evidenced by mitochondrial damage and membrane depolarization.
- In a mouse model, FOR0212A reduced parasitemia by 50.2% without toxicity.

## Abstract

Chagas disease remains a significant global health concern,
with
current therapies limited to benznidazole and nifurtimox, which have
adverse effects and show reduced efficacy in the chronic phase. This
study investigated ruthenium complexes with or without thiobenzamide
(Tbz). FOR0012A and FOR0212A, both containing Tbz, showed potent trypanocidal
activity, with IC50 values of 0.13 and 0.09 μM for
trypomastigotes, and 1.8 and 0.32 μM for amastigotes. Electron
microscopy revealed shrinkage, blebbing, and severe mitochondrial/kinetoplast
damage, indicating apoptosis-like cell death, as confirmed by flow
cytometry. Docking studies demonstrated strong binding to trypanothione
reductase, suggesting oxidative stress induction, further supported
by mitochondrial superoxide production and membrane depolarization.
In a murine model, FOR0212A (20 mg/kg) reduced parasitemia by 50.2%
during the acute phase without any toxicity. These findings identify
FOR0212A as a promising therapeutic candidate for Chagas disease,
acting via oxidative stress and apoptosis-like mechanisms in T. cruzi.