# Development of Novel Peptidyl Nitriles Targeting Rhodesain and Falcipain-2 for the Treatment of Sleeping Sickness and Malaria

## TL;DR

This paper presents a new compound that can target two enzymes involved in sleeping sickness and malaria, offering potential for new treatments.

## Contribution

The study introduces a novel lead compound effective against rhodesain and falcipain-2, key targets for treating sleeping sickness and malaria.

## Key findings

- Inhibitor 2b showed a Ki of 5.06 µM against rhodesain.
- The compound had an IC50 of 40.43 µM against falcipain-2.

## Abstract

In recent decades, neglected tropical diseases and poverty-related diseases have become a serious health problem worldwide. Among these pathologies, human African trypanosomiasis, and malaria present therapeutic problems due to the onset of resistance, toxicity problems and the limited spectrum of action. In this drug discovery process, rhodesain and falcipain-2, of Trypanosoma brucei rhodesiense and Plasmodium falciparum, are currently considered the most promising targets for the development of novel antitrypanosomal and antiplasmodial agents, respectively. Therefore, in our study we identified a novel lead-like compound, i.e., inhibitor 2b, which we proved to be active against both targets, with a Ki = 5.06 µM towards rhodesain and an IC50 = 40.43 µM against falcipain-2.