Antimicrobial and antiparasitic potential of lupeol: antifungal effect on the Candida parapsilosis species complex and nematicidal activity against Caenorhabditis elegans

<b>Introduction.</b> There is growing concern about infections caused by non-<i>albicans Candida</i> species, including species of the <i>Candida parapsilosis</i> complex - which have seen a considerable increase in cases during the COVID-19 pandemic - in addition to concern about nematode resistance to currently used anthelmintics.<b>Gap Statement.</b> Lupeol is a triterpenoid phytosterol that has a wide range of biological activities, although its antifungal and antiparasitic potential is still poorly explored. Additionally, its effect on the biofilm of the <i>C. parapsilosis</i> species complex has not yet been studied.<b>Aim.</b> This study aimed to investigate the antifungal effect of lupeol against <i>C. parapsilosis</i> complex species, in planktonic cells and mature biofilms, as well as its nematicidal potential against <i>Caenorhabditis elegans</i>. In addition, molecular docking was performed to identify potential target molecules for lupeol's antifungal effect.<b>Methodology.</b> Twelve strains of <i>C. parapsilosis</i> species complex were used. Planktonic susceptibility was performed through the broth microdilution assay, while the antibiofilm effect was investigated by measuring the biomass and metabolic activity. The antifungal mechanism of action of lupeol was investigated by target fishing. The evaluation of the nematicidal effect was performed using the <i>C. elegans</i> infection model.<b>Results.</b> Lupeol demonstrated antifungal activity against planktonic cells with a MIC between 64 and 512 µg ml^-1. In mature biofilms, lupeol was able to reduce biomass starting from a concentration of 1024 µg ml^-1 and reduce metabolic activity from a concentration of 64 µg ml^-1. It was observed that there was interaction of lupeol with the enzyme 14α-demethylase. Furthermore, lupeol had a nematicidal effect from a concentration of 64 µg ml^-1.<b>Conclusion.</b> Lupeol exhibits an antifungal effect on the <i>C. parapsilosis</i> species complex, in the planktonic and mature biofilm forms, possibly by affecting the ergosterol synthesis. Lupeol further demonstrated a nematicidal potential.