# Bioprospecting for Anti-Kinetoplastid Drug Discovery from Aloysia citrodora Essential Oil

## TL;DR

This study explores the anti-parasitic potential of Aloysia citrodora essential oil, identifying citral and its derivatives as promising drug candidates for treating Chagas disease and leishmaniasis.

## Contribution

The study identifies citral and its derivative as novel anti-kinetoplastid compounds with potential for treating neglected tropical diseases.

## Key findings

- Citral (compound 1) showed strong anti-kinetoplastid activity with IC50 values of 8.47 μM and 12.90 μM against L. amazonensis and T. cruzi, respectively.
- Citral 2,4-dinitrophenylhydrazone (compound 9) exhibited the highest activity with an IC50 of 10.62 μM against L. amazonensis.
- Compound 9 induces programmed cell death by targeting the apoptotic pathway.

## Abstract

Natural products have long been recognized as invaluable resources in drug discovery. Essential oils have attracted widespread attention due to their broad spectrum of biological activities. Herein, we report the anti-kinetoplastid activity of Aloysia citrodora leaf essential oil through a bioassay-guided fractionation method against the etiological agents of Chagas disease and leishmaniasis. This approach has led to the isolation and structural identification of compound 1 (citral) as the main active constituent, with IC50 values of 8.47 μM against Leishmania amazonensis and 12.90 μM against Trypanosoma cruzi. In addition, eight compounds (2–9) were synthesized and evaluated. Among these, citral 2,4-dinitrophenylhydrazone (9) exhibited the highest anti-kinetoplastid activity, with an IC50 value of 10.62 μM against L. amazonensis, displaying a similar biological profile to citral and the reference drug. Structure–activity relationship studies revealed that the type of Schiff base and acylating agent played a crucial role in the activity. Mechanism of action studies demonstrated that compound 9 directly targets the apoptotic pathway, inducing programmed cell death through selective pathway inhibition. This work underscores the potential of A. citrodora essential oil and its compounds as prospective therapeutic leads against neglected tropical diseases.