# Screening of synthetic 1,2,3-triazolic compounds inspired by SRPIN340 as anti-Trypanosoma cruzi agents

## TL;DR

Researchers tested new triazole compounds against the parasite causing Chagas disease and found two promising candidates with strong activity.

## Contribution

Identification of two new triazole compounds with high in vitro and in vivo efficacy against Trypanosoma cruzi.

## Key findings

- Eight compounds showed in vitro activity with IC50 values between 0.5-10.5 µg/mL.
- Compounds 6E and 6H had selectivity indexes of 125.2 and 69.6, respectively.
- 6E and 6H reduced parasitemia in infected mice at doses of 50 and 250 mg/kg/day.

## Abstract

The current treatments for Chagas disease (CD) include benznidazole and
nifurtimox, which have limited efficacy and cause numerous side effects.
Triazoles are candidates for new CD treatments due to their ability to
eliminate T. cruzi parasites by inhibiting ergosterol
synthesis, thereby damaging the cell membranes of the parasite.

Eleven synthetic analogs of the kinase inhibitor SRPIN340 containing a
triazole core (compounds 6A-6K) were screened
in vitro against the Tulahuen strain transfected with
β-galactosidase, and their IC50, CC50, and selectivity indexes (SI) were
calculated. Compounds with an SI > 50 were further evaluated in mice
infected with the T. cruzi Y strain by rapid testing.

Eight compounds were active in vitro with IC50 values
ranging from 0.5-10.5 µg/mL. The most active compounds, 6E and
6H, had SI values of 125.2 and 69.6, respectively. These
compounds also showed in vivo activity, leading to a
reduction in parasitemia at doses of 10, 50, and 250 mg/kg/day. At doses of
50 and 250 mg/kg/day, parasitemia was significantly reduced compared to
infected untreated animals, with no significant differences between the
effects of 6E and 6H.

This study identified two new promising compounds for CD chemotherapy and
confirmed their activity against T. cruzi.