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

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 [IC 50 ]: 22.8–25.2 µg/mL). EOJ also exhibited cytotoxic effects on HCT‐116 and PC‐3 cell lines (IC 50 : 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.