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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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.
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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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