# Synthesis and Biological Evaluation of Tetrahydroisoquinoline Derivatives as Trypanocidal Agents

## TL;DR

This paper presents new tetrahydroisoquinoline compounds with antiparasitic activity against Trypanosoma cruzi, which causes American trypanosomiasis.

## Contribution

The study introduces novel tetrahydroisoquinoline derivatives with potent antiparasitic effects that do not target cruzain.

## Key findings

- Compound 3d and its hydrochloride salt 4d showed strong antiparasitic activity with IC50 values of 10.5 and 13.7 μM.
- These compounds exhibited low cruzain inhibition, suggesting a different mechanism of action.
- Hydrochloride salts 4a and 4b moderately inhibited cruzain with 60.2% and 69.3% inhibition at 100 μM.

## Abstract

American trypanosomiasis
is a parasitic illness of major public
health relevance, resulting from infection with the protozoan Trypanosoma cruzi and predominantly impacting populations
in low-resource settings. Current treatments, benznidazole and nifurtimox,
are limited by their efficacy in the chronic phase, toxicity, and
side effects, necessitating the search for new therapeutic agents.
Cruzain, a key protease for parasite survival and infection, is a
validated drug target. This work involved the synthesis and characterization
of novel amides derived from 1,2,3,4-tetrahydroisoquinoline-3-carboxylic
acid. Their activity was evaluated against both cruzain and T. cruzi. The hydrochloride salts 4a and 4b showed moderate cruzain inhibition (60.2 ±
2.4% and 69.3 ± 2.6% inhibition at 100 μM, respectively).
Notably, compound 3d and its hydrochloride salt 4d demonstrated significant antiparasitic activity with IC50 values of 10.5 and 13.7 μM, respectively. However,
their low cruzain inhibition (∼15%) suggests that their mechanism
of action is likely through a different biological target.