Anticandidal activity of Clinopodium chilense essential oil

<jats:p>The antifungal activity of the essential oil of <jats:italic>Clinopodium chilense</jats:italic> (Benth.) Govaerts was investigated against several strains of <jats:italic>Candida</jats:italic> spp. including clinical isolates and reference strains. Antifungal efficacy was evaluated by determining minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC). The chemical composition of the essential oil, characterized by gas chromatography-mass spectrometry (GC/MS), revealed pulegone (18.5%), thymol (11.0%), and isomenthone (10.0%) as the primary constituents. <jats:italic>Clinopodium chilense</jats:italic> essential oil (EO) demonstrated broad-spectrum anticandidal activity against all tested <jats:italic>Candida</jats:italic> spp., with MIC values ranging from 16 to 64 μg/mL and MFC values from 16 to 128 μg/mL. The EO exhibited potent fungicidal activity (MFC/MIC ratio ≤2) against several strains, notably <jats:italic>Candida tropicalis</jats:italic> (MIC and MFC of 16 μg/mL), and also showed efficacy against <jats:italic>C. guilliermondii</jats:italic> and <jats:italic>C. lusitaniae</jats:italic>. Among the major components, thymol generally displayed the lowest MIC values (32–64 μg/mL). Molecular docking studies further suggested thymol as a key contributor to the oil’s antifungal effect, showing strong binding affinities to <jats:italic>C. albicans</jats:italic> virulence proteins Als9-2 and the enzyme CYP51. Significantly, the essential oil outperformed amphotericin B against all tested clinical isolates. Overall, <jats:italic>C. chilense</jats:italic> EO exhibits significant fungistatic and fungicidal activity against pathogenic <jats:italic>Candida</jats:italic> species without affecting normal cell viability. These findings, supported by chemical characterization and <jats:italic>in silico</jats:italic> analysis of its major components like thymol, highlight its potential as a source of novel natural antifungal agents.</jats:p>