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Enhancing the Antifungal Efficacy of Fluconazole with a Diterpene: Abietic Acid as a Promising Adjuvant to Combat Antifungal Resistance in Candida 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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10668680/ https://www.ncbi.nlm.nih.gov/pubmed/37998767 http://dx.doi.org/10.3390/antibiotics12111565 |
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author | 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 |
author_facet | 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 |
author_sort | de Lima Silva, Maria Gabriely |
collection | PubMed |
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 Pinus species, has significant antimicrobial properties, this study aimed to evaluate the antifungal activity of abietic acid against Candida spp and its ability to potentiate the activity of fluconazole. Abietic acid was tested both individually and in combination with fluconazole against Candida albicans (CA INCQS 40006), Candida krusei (CK INCQS 40095), and Candida tropicalis (CT INCQS 40042). The microdilution method was used to determine the IC(50) 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(50) of the drugs alone ranged between 1065 and 3255 μg/mL, the IC(50) 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 Candida albicans, Candida krusei and Candida tropicalis. However, it was observed that the antifungal effect of fluconazole was enhanced when used in combination with abietic acid against Candida albicans and Candida tropicalis. These findings suggest that while abietic acid alone has limited inherent antifungal activity, it can enhance the effectiveness of fluconazole, thereby reducing antifungal resistance. |
format | Online Article Text |
id | pubmed-10668680 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-106686802023-10-26 Enhancing the Antifungal Efficacy of Fluconazole with a Diterpene: Abietic Acid as a Promising Adjuvant to Combat Antifungal Resistance in Candida spp. 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 Antibiotics (Basel) Article 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 Pinus species, has significant antimicrobial properties, this study aimed to evaluate the antifungal activity of abietic acid against Candida spp and its ability to potentiate the activity of fluconazole. Abietic acid was tested both individually and in combination with fluconazole against Candida albicans (CA INCQS 40006), Candida krusei (CK INCQS 40095), and Candida tropicalis (CT INCQS 40042). The microdilution method was used to determine the IC(50) 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(50) of the drugs alone ranged between 1065 and 3255 μg/mL, the IC(50) 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 Candida albicans, Candida krusei and Candida tropicalis. However, it was observed that the antifungal effect of fluconazole was enhanced when used in combination with abietic acid against Candida albicans and Candida tropicalis. These findings suggest that while abietic acid alone has limited inherent antifungal activity, it can enhance the effectiveness of fluconazole, thereby reducing antifungal resistance. MDPI 2023-10-26 /pmc/articles/PMC10668680/ /pubmed/37998767 http://dx.doi.org/10.3390/antibiotics12111565 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article 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 Enhancing the Antifungal Efficacy of Fluconazole with a Diterpene: Abietic Acid as a Promising Adjuvant to Combat Antifungal Resistance in Candida spp. |
title | Enhancing the Antifungal Efficacy of Fluconazole with a Diterpene: Abietic Acid as a Promising Adjuvant to Combat Antifungal Resistance in Candida spp. |
title_full | Enhancing the Antifungal Efficacy of Fluconazole with a Diterpene: Abietic Acid as a Promising Adjuvant to Combat Antifungal Resistance in Candida spp. |
title_fullStr | Enhancing the Antifungal Efficacy of Fluconazole with a Diterpene: Abietic Acid as a Promising Adjuvant to Combat Antifungal Resistance in Candida spp. |
title_full_unstemmed | Enhancing the Antifungal Efficacy of Fluconazole with a Diterpene: Abietic Acid as a Promising Adjuvant to Combat Antifungal Resistance in Candida spp. |
title_short | Enhancing the Antifungal Efficacy of Fluconazole with a Diterpene: Abietic Acid as a Promising Adjuvant to Combat Antifungal Resistance in Candida spp. |
title_sort | enhancing the antifungal efficacy of fluconazole with a diterpene: abietic acid as a promising adjuvant to combat antifungal resistance in candida spp. |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10668680/ https://www.ncbi.nlm.nih.gov/pubmed/37998767 http://dx.doi.org/10.3390/antibiotics12111565 |
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