AUTHOR=Montenegro Iván , Villarroel Constanza , Muñoz Evelyn , Mena-Ulecia Karel , Silva Valentina , Madrid Alejandro TITLE=Anticandidal activity of Clinopodium chilense essential oil JOURNAL=Frontiers in Pharmacology VOLUME=Volume 16 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1634250 DOI=10.3389/fphar.2025.1634250 ISSN=1663-9812 ABSTRACT=The antifungal activity of the essential oil of Clinopodium chilense (Benth.) Govaerts was investigated against several strains of Candida 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. Clinopodium chilense essential oil (EO) demonstrated broad-spectrum anticandidal activity against all tested Candida 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 Candida tropicalis (MIC and MFC of 16 μg/mL), and also showed efficacy against C. guilliermondii and C. lusitaniae. 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 C. albicans virulence proteins Als9-2 and the enzyme CYP51. Significantly, the essential oil outperformed amphotericin B against all tested clinical isolates. Overall, C. chilense EO exhibits significant fungistatic and fungicidal activity against pathogenic Candida species without affecting normal cell viability. These findings, supported by chemical characterization and in silico analysis of its major components like thymol, highlight its potential as a source of novel natural antifungal agents.