# Biological Effects of Novel Synthetic Guanidine Derivatives Targeting Leishmania (Viannia) braziliensis

## TL;DR

This study explores new guanidine compounds that show promise as safe and effective treatments for Leishmaniasis, a tropical disease.

## Contribution

The study introduces novel guanidine derivatives with high selectivity and potency against Leishmania (Viannia) braziliensis.

## Key findings

- FURL-G5 showed potent activity against promastigote forms with high selectivity indices.
- Compounds reduced intracellular amastigote infection rates in macrophages.
- In silico and in vitro approaches enabled effective prioritization of drug candidates.

## Abstract

Leishmaniasis remains an important neglected tropical disease, and current treatments are limited by toxicity, resistance, and low bioavailability. In this study, novel guanidine derivatives were evaluated through an integrated approach, combining in silico physicochemical profiling with in vitro biological assays using Leishmania (Viannia) braziliensis, the etiological agent of American Tegumentary Leishmaniasis (ATL). Most compounds exhibited favorable drug-like properties, though variations in lipophilicity and solubility influenced biological performance. Among the tested molecules, FURL-G5 emerged as the most promising candidate, showing potent activity against promastigote forms and low cytotoxicity in murine macrophages, resulting in high selectivity indices (SI > 10), comparable to those of LQOF-G1, a compound with previously established leishmanicidal effects. These compounds were also tested on intracellular amastigotes, drastically reducing the infection rate of macrophages. The integration of an in silico approach and biological validation enabled rational compound prioritization and supports the early-stage development of these scaffolds. Overall, this study reinforces the potential of guanidine-based compounds as leads for innovative ATL drug discovery and demonstrates the value of multidisciplinary strategies for identifying selective and safe therapeutic candidates.