Enhancing the Antifungal Efficacy of Fluconazole with a Diterpene: Abietic Acid as a Promising Adjuvant to Combat Antifungal Resistance in spp.

The increasing antifungal resistance rates against conventional drugs reveal the urgent need to search for new therapeutic alternatives. In this context, natural bioactive compounds have a critical role in antifungal drug development. Since evidence demonstrates that abietic acid, a diterpene found in species, has significant antimicrobial properties, this study aimed to evaluate the antifungal activity of abietic acid against spp and its ability to potentiate the activity of fluconazole. Abietic acid was tested both individually and in combination with fluconazole against (CA INCQS 40006), (CK INCQS 40095), and (CT INCQS 40042). The microdilution method was used to determine the IC and the cell viability curve. Minimum Fungicidal Concentration (MFC) was determined by subculture in a solid medium. The plasma membrane permeability was measured using a fluorescent SYTOX Green probe. While the IC of the drugs alone ranged between 1065 and 3255 μg/mL, the IC resulting from the combination of abietic acid and fluconazole ranged between 7563 and 160.1 μg/mL. Whether used in combination with fluconazole or isolated, abietic acid exhibited Minimum Fungicidal Concentration (MFC) values exceeding 1024 μg/mL against , and . However, it was observed that the antifungal effect of fluconazole was enhanced when used in combination with abietic acid against and . These findings suggest that while abietic acid alone has limited inherent antifungal activity, it can enhance the effectiveness of fluconazole, thereby reducing antifungal resistance.