# Cytotoxic and Antileishmanial Potential of Pilocarpus microphyllus Essential Oil: In Vitro and In Silico Study

## TL;DR

This study explores the antifungal, antileishmanial, and anticancer properties of Pilocarpus microphyllus essential oil and identifies its key chemical components.

## Contribution

The study identifies γ-cadinene and trans-caryophyllene as key bioactive compounds in Pilocarpus microphyllus essential oil with multitarget therapeutic potential.

## Key findings

- EOJ showed antifungal activity against Cryptococcus neoformans with MIC values of 149–2395 µg/mL.
- The oil exhibited antileishmanial activity against Leishmania amazonensis with an IC50 of 22.8–25.2 µg/mL.
- γ-cadinene and trans-caryophyllene showed strong in silico binding to therapeutic targets Nectin-4 and lanosterol 14α-demethylase.

## Abstract

The essential oil of Pilocarpus microphyllus (jaborandi) (EOJ), a species traditionally recognized for its alkaloid‐based pharmacological properties, remains poorly investigated despite its richness in bioactive terpenes. In this study, the chemical profile of EOJ obtained from fresh and dried leaves was determined by gas chromatography‐mass spectrometry, revealing 24 constituents, predominantly γ‐cadinene (23.6%) and trans‐caryophyllene (22.9%). Antifungal activity was observed against Cryptococcus neoformans (minimum inhibitory concentration: 149−2395 µg/mL), while antileishmanial potential was confirmed against Leishmania amazonensis promastigotes (half‐maximal inhibitory concentration [IC50]: 22.8–25.2 µg/mL). EOJ also exhibited cytotoxic effects on HCT‐116 and PC‐3 cell lines (IC50: 27.8–29.2 µg/mL). In silico studies revealed strong binding affinities with therapeutic targets: γ‐cadinene to Nectin‐4 (ΔG = −7.3 kcal/mol) and trans‐caryophyllene to lanosterol 14α‐demethylase (ΔG = −5.7 kcal/mol). Absorption, distribution, metabolism, excretion, and toxicity predictions indicated favorable oral absorption and low genotoxicity. Altogether, EOJ demonstrates multitarget bioactivity, and its major constituents represent promising leads for antifungal, antileishmanial, and anticancer drug development.

Jaborandi (Pilocarpus microphyllus) essential oil is obtained by removal and characterization using GC‐MS, revealing γ‐cadinene and trans‐caryophyllene as major constituents. The oil exhibits biological activity, with antifungal action against Candida spp. and Cryptococcus spp., as well as antipromastigote activity against Leishmania amazonensis. Furthermore, cytotoxic effects are observed in the HCT‐116 and PC‐3 cell lines.