Enhancing the Antifungal Efficacy of Fluconazole with a Diterpene: Abietic Acid as a Promising Adjuvant to Combat Antifungal Resistance in <i>Candida</i> 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...
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| Language: | English |
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MDPI AG
2023-10-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/12/11/1565 |
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| author | Maria Gabriely de Lima Silva Luciene Ferreira de Lima Victor Juno Alencar Fonseca Lucas Yure Santos da Silva Ana Cecília Calixto Donelardy Ray Silva de Almeida Cícera Datiane de Morais Oliveira-Tintino Anita Oliveira Brito Pereira Bezerra Martins Jaime Ribeiro-Filho Maria Flaviana Bezerra Morais-Braga Saulo Relison Tintino Irwin Rose Alencar de Menezes |
| author_facet | Maria Gabriely de Lima Silva Luciene Ferreira de Lima Victor Juno Alencar Fonseca Lucas Yure Santos da Silva Ana Cecília Calixto Donelardy Ray Silva de Almeida Cícera Datiane de Morais Oliveira-Tintino Anita Oliveira Brito Pereira Bezerra Martins Jaime Ribeiro-Filho Maria Flaviana Bezerra Morais-Braga Saulo Relison Tintino Irwin Rose Alencar de Menezes |
| author_sort | Maria Gabriely de Lima Silva |
| collection | DOAJ |
| description | 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 <i>Pinus</i> species, has significant antimicrobial properties, this study aimed to evaluate the antifungal activity of abietic acid against <i>Candida</i> spp and its ability to potentiate the activity of fluconazole. Abietic acid was tested both individually and in combination with fluconazole against <i>Candida albicans</i> (CA INCQS 40006), <i>Candida krusei</i> (CK INCQS 40095), and <i>Candida tropicalis</i> (CT INCQS 40042). The microdilution method was used to determine the IC<sub>50</sub> 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<sub>50</sub> of the drugs alone ranged between 1065 and 3255 μg/mL, the IC<sub>50</sub> 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 <i>Candida albicans</i>, <i>Candida krusei</i> and <i>Candida tropicalis</i>. However, it was observed that the antifungal effect of fluconazole was enhanced when used in combination with abietic acid against <i>Candida albicans</i> and <i>Candida tropicalis</i>. These findings suggest that while abietic acid alone has limited inherent antifungal activity, it can enhance the effectiveness of fluconazole, thereby reducing antifungal resistance. |
| first_indexed | 2024-03-09T17:05:49Z |
| format | Article |
| id | doaj.art-c5d1517b34914823b88ee6f18f8faac3 |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-09T17:05:49Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-c5d1517b34914823b88ee6f18f8faac32023-11-24T14:25:07ZengMDPI AGAntibiotics2079-63822023-10-011211156510.3390/antibiotics12111565Enhancing the Antifungal Efficacy of Fluconazole with a Diterpene: Abietic Acid as a Promising Adjuvant to Combat Antifungal Resistance in <i>Candida</i> spp.Maria Gabriely de Lima Silva0Luciene Ferreira de Lima1Victor Juno Alencar Fonseca2Lucas Yure Santos da Silva3Ana Cecília Calixto Donelardy4Ray Silva de Almeida5Cícera Datiane de Morais Oliveira-Tintino6Anita Oliveira Brito Pereira Bezerra Martins7Jaime Ribeiro-Filho8Maria Flaviana Bezerra Morais-Braga9Saulo Relison Tintino10Irwin Rose Alencar de Menezes11Laboratory of Pharmacology and Molecular Chemistry (LFQM), Department of Biological Chemistry, Regional University of Cariri (URCA), Crato 63105-000, Ceará, BrazilLaboratory of Applied Mycology of Cariri (LMAC), Regional University of Cariri (URCA), Crato 63105-000, Ceará, BrazilLaboratory of Applied Mycology of Cariri (LMAC), Regional University of Cariri (URCA), Crato 63105-000, Ceará, BrazilLaboratory of Pharmacology and Molecular Chemistry (LFQM), Department of Biological Chemistry, Regional University of Cariri (URCA), Crato 63105-000, Ceará, BrazilLaboratory of Pharmacology and Molecular Chemistry (LFQM), Department of Biological Chemistry, Regional University of Cariri (URCA), Crato 63105-000, Ceará, BrazilLaboratory of Microbiology and Molecular Biology (LMBM), Regional University of Cariri (URCA), Crato 63105-000, Ceará, BrazilLaboratory of Microbiology and Molecular Biology (LMBM), Regional University of Cariri (URCA), Crato 63105-000, Ceará, BrazilLaboratory of Pharmacology and Molecular Chemistry (LFQM), Department of Biological Chemistry, Regional University of Cariri (URCA), Crato 63105-000, Ceará, BrazilOswaldo Cruz Foundation (Fiocruz), Fiocruz Ceará, Eusébio 61773-270, Ceará, BrazilLaboratory of Applied Mycology of Cariri (LMAC), Regional University of Cariri (URCA), Crato 63105-000, Ceará, BrazilLaboratory of Microbiology and Molecular Biology (LMBM), Regional University of Cariri (URCA), Crato 63105-000, Ceará, BrazilLaboratory of Pharmacology and Molecular Chemistry (LFQM), Department of Biological Chemistry, Regional University of Cariri (URCA), Crato 63105-000, Ceará, BrazilThe 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 <i>Pinus</i> species, has significant antimicrobial properties, this study aimed to evaluate the antifungal activity of abietic acid against <i>Candida</i> spp and its ability to potentiate the activity of fluconazole. Abietic acid was tested both individually and in combination with fluconazole against <i>Candida albicans</i> (CA INCQS 40006), <i>Candida krusei</i> (CK INCQS 40095), and <i>Candida tropicalis</i> (CT INCQS 40042). The microdilution method was used to determine the IC<sub>50</sub> 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<sub>50</sub> of the drugs alone ranged between 1065 and 3255 μg/mL, the IC<sub>50</sub> 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 <i>Candida albicans</i>, <i>Candida krusei</i> and <i>Candida tropicalis</i>. However, it was observed that the antifungal effect of fluconazole was enhanced when used in combination with abietic acid against <i>Candida albicans</i> and <i>Candida tropicalis</i>. These findings suggest that while abietic acid alone has limited inherent antifungal activity, it can enhance the effectiveness of fluconazole, thereby reducing antifungal resistance.https://www.mdpi.com/2079-6382/12/11/1565anti-<i>Candida</i> activityabietic acidfluconazoleantifungal resistance |
| spellingShingle | Maria Gabriely de Lima Silva Luciene Ferreira de Lima Victor Juno Alencar Fonseca Lucas Yure Santos da Silva Ana Cecília Calixto Donelardy Ray Silva de Almeida Cícera Datiane de Morais Oliveira-Tintino Anita Oliveira Brito Pereira Bezerra Martins Jaime Ribeiro-Filho Maria Flaviana Bezerra Morais-Braga Saulo Relison Tintino Irwin Rose Alencar de Menezes Enhancing the Antifungal Efficacy of Fluconazole with a Diterpene: Abietic Acid as a Promising Adjuvant to Combat Antifungal Resistance in <i>Candida</i> spp. Antibiotics anti-<i>Candida</i> activity abietic acid fluconazole antifungal resistance |
| title | Enhancing the Antifungal Efficacy of Fluconazole with a Diterpene: Abietic Acid as a Promising Adjuvant to Combat Antifungal Resistance in <i>Candida</i> spp. |
| title_full | Enhancing the Antifungal Efficacy of Fluconazole with a Diterpene: Abietic Acid as a Promising Adjuvant to Combat Antifungal Resistance in <i>Candida</i> spp. |
| title_fullStr | Enhancing the Antifungal Efficacy of Fluconazole with a Diterpene: Abietic Acid as a Promising Adjuvant to Combat Antifungal Resistance in <i>Candida</i> spp. |
| title_full_unstemmed | Enhancing the Antifungal Efficacy of Fluconazole with a Diterpene: Abietic Acid as a Promising Adjuvant to Combat Antifungal Resistance in <i>Candida</i> spp. |
| title_short | Enhancing the Antifungal Efficacy of Fluconazole with a Diterpene: Abietic Acid as a Promising Adjuvant to Combat Antifungal Resistance in <i>Candida</i> spp. |
| title_sort | enhancing the antifungal efficacy of fluconazole with a diterpene abietic acid as a promising adjuvant to combat antifungal resistance in i candida i spp |
| topic | anti-<i>Candida</i> activity abietic acid fluconazole antifungal resistance |
| url | https://www.mdpi.com/2079-6382/12/11/1565 |
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