de Lima Silva Maria Gabriely, de Lima Luciene Ferreira, Alencar Fonseca Victor Juno, Santos da Silva Lucas Yure, Calixto Donelardy Ana Cecília, de Almeida Ray Silva, de Morais Oliveira-Tintino Cícera Datiane, Pereira Bezerra Martins Anita Oliveira Brito, Ribeiro-Filho Jaime, Bezerra Morais-Braga Maria Flaviana, Tintino Saulo Relison, Alencar de Menezes Irwin Rose
Laboratory of Pharmacology and Molecular Chemistry (LFQM), Department of Biological Chemistry, Regional University of Cariri (URCA), Crato 63105-000, Ceará, Brazil.
Laboratory of Applied Mycology of Cariri (LMAC), Regional University of Cariri (URCA), Crato 63105-000, Ceará, Brazil.
Antibiotics (Basel). 2023 Oct 26;12(11):1565. doi: 10.3390/antibiotics12111565.
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.
对传统药物的抗真菌耐药率不断上升，这表明迫切需要寻找新的治疗方法。在这种背景下，天然生物活性化合物在抗真菌药物开发中起着关键作用。由于有证据表明，在某些物种中发现的二萜类化合物枞酸具有显著的抗菌特性，本研究旨在评估枞酸对白色念珠菌、光滑念珠菌和热带念珠菌的抗真菌活性及其增强氟康唑活性的能力。分别单独测试了枞酸以及将其与氟康唑联合，用于对抗白色念珠菌（CA INCQS 40006）、光滑念珠菌（CK INCQS 40095）和热带念珠菌（CT INCQS 40042）。采用微量稀释法测定半数抑制浓度（IC）和细胞活力曲线。通过在固体培养基中传代培养来确定最低杀菌浓度（MFC）。使用荧光SYTOX Green探针测量质膜通透性。单独使用药物时，半数抑制浓度（IC）在1065至3255μg/mL之间，而枞酸与氟康唑联合使用时，半数抑制浓度（IC）在7563至160.1μg/mL之间。无论与氟康唑联合使用还是单独使用，枞酸对白色念珠菌、光滑念珠菌和热带念珠菌的最低杀菌浓度（MFC）值均超过1024μg/mL。然而，观察到当氟康唑与枞酸联合使用时，对白色念珠菌和光滑念珠菌的抗真菌效果增强。这些发现表明，虽然枞酸单独的固有抗真菌活性有限，但它可以增强氟康唑的有效性，从而降低抗真菌耐药性。
