A Potent Fluorescent Derivative of 8-Hydroxyquinoline Suggests Cell Wall Damage as a Possible Cellular Action of the 5-Triazole 8-Hydroxyquinoline Class

Fungal infections are a major but often neglected global health challenge, affecting both human health and agricultural productivity. Current treatments are limited by few drug classes and increasing multidrug resistance, exacerbated by the widespread use of antifungal agents in clinical and agricul...

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Main Authors: Caroline de Bem Gentz, Marcela Silva Lopes, Priscilla Maciel Quatrin, Mariana Pies Gionbelli, Maycon Antonio de Cesare, Ana Paula Perin, William Lopes, Alexandre Meneghello Fuentefria, Marilene Henning Vainstein, Saulo Fernandes de Andrade
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Applied Microbiology
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Online Access:https://www.mdpi.com/2673-8007/5/2/38
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author Caroline de Bem Gentz
Marcela Silva Lopes
Priscilla Maciel Quatrin
Mariana Pies Gionbelli
Maycon Antonio de Cesare
Ana Paula Perin
William Lopes
Alexandre Meneghello Fuentefria
Marilene Henning Vainstein
Saulo Fernandes de Andrade
author_facet Caroline de Bem Gentz
Marcela Silva Lopes
Priscilla Maciel Quatrin
Mariana Pies Gionbelli
Maycon Antonio de Cesare
Ana Paula Perin
William Lopes
Alexandre Meneghello Fuentefria
Marilene Henning Vainstein
Saulo Fernandes de Andrade
author_sort Caroline de Bem Gentz
collection DOAJ
description Fungal infections are a major but often neglected global health challenge, affecting both human health and agricultural productivity. Current treatments are limited by few drug classes and increasing multidrug resistance, exacerbated by the widespread use of antifungal agents in clinical and agricultural settings. This study investigates the antifungal potential of a novel 8-hydroxyquinoline derivative with a triazole core at the 5-position, synthesized to improve both efficacy and mechanistic understanding as a fluorescent chemical probe. Biological assays demonstrated significant antifungal activity of compound <b>10</b> against a range of pathogens, which was active against all <i>Candida</i> species, dermatophytes, and <i>Fusarium solani</i> with MIC values ranging from 0.5 to 4 µg/mL. Confocal fluorescence microscopy of treated fungal cells was conducted and showed a high accumulation of compound <b>10</b> at the cell edge. To further investigate the mode of action, results from a sorbitol protection assay suggested a possible cell wall action, and scanning electron microscopy (SEM) revealed cell wall disruption, such as cell shrinkage and surface roughness, in treated fungal cells. These findings highlight the 8-hydroxyquinoline-triazole scaffold as a promising antifungal agent with cell wall damage properties, providing a basis for future therapeutic development against human and plant fungal pathogens.
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institution Kabale University
issn 2673-8007
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publishDate 2025-04-01
publisher MDPI AG
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series Applied Microbiology
spelling doaj-art-76c52e73ef3a4c5e9c66f0653d85cba12025-08-20T03:26:25ZengMDPI AGApplied Microbiology2673-80072025-04-01523810.3390/applmicrobiol5020038A Potent Fluorescent Derivative of 8-Hydroxyquinoline Suggests Cell Wall Damage as a Possible Cellular Action of the 5-Triazole 8-Hydroxyquinoline ClassCaroline de Bem Gentz0Marcela Silva Lopes1Priscilla Maciel Quatrin2Mariana Pies Gionbelli3Maycon Antonio de Cesare4Ana Paula Perin5William Lopes6Alexandre Meneghello Fuentefria7Marilene Henning Vainstein8Saulo Fernandes de Andrade9Agricultural and Environmental Microbiology Graduate Program, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-003, BrazilPharmaceutical Sciences Graduate Program, Universidade Federal do Rio Grande do Sul, Porto Alegre 90160-093, BrazilAgricultural and Environmental Microbiology Graduate Program, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-003, BrazilPharmaceutical Sciences Graduate Program, Universidade Federal do Rio Grande do Sul, Porto Alegre 90160-093, BrazilPharmaceutical Sciences Graduate Program, Universidade Federal do Rio Grande do Sul, Porto Alegre 90160-093, BrazilDepartment of Molecular Biology and Biotechnology, Universidade Federal do Rio Grande do Sul, Porto Alegre 91501-970, BrazilPhysics of Living Systems, Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139, USAAgricultural and Environmental Microbiology Graduate Program, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-003, BrazilDepartment of Molecular Biology and Biotechnology, Universidade Federal do Rio Grande do Sul, Porto Alegre 91501-970, BrazilAgricultural and Environmental Microbiology Graduate Program, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-003, BrazilFungal infections are a major but often neglected global health challenge, affecting both human health and agricultural productivity. Current treatments are limited by few drug classes and increasing multidrug resistance, exacerbated by the widespread use of antifungal agents in clinical and agricultural settings. This study investigates the antifungal potential of a novel 8-hydroxyquinoline derivative with a triazole core at the 5-position, synthesized to improve both efficacy and mechanistic understanding as a fluorescent chemical probe. Biological assays demonstrated significant antifungal activity of compound <b>10</b> against a range of pathogens, which was active against all <i>Candida</i> species, dermatophytes, and <i>Fusarium solani</i> with MIC values ranging from 0.5 to 4 µg/mL. Confocal fluorescence microscopy of treated fungal cells was conducted and showed a high accumulation of compound <b>10</b> at the cell edge. To further investigate the mode of action, results from a sorbitol protection assay suggested a possible cell wall action, and scanning electron microscopy (SEM) revealed cell wall disruption, such as cell shrinkage and surface roughness, in treated fungal cells. These findings highlight the 8-hydroxyquinoline-triazole scaffold as a promising antifungal agent with cell wall damage properties, providing a basis for future therapeutic development against human and plant fungal pathogens.https://www.mdpi.com/2673-8007/5/2/388-hydroxyquinolinetriazoleantifungal activitycell wall actionfluorescencemicroscopy
spellingShingle Caroline de Bem Gentz
Marcela Silva Lopes
Priscilla Maciel Quatrin
Mariana Pies Gionbelli
Maycon Antonio de Cesare
Ana Paula Perin
William Lopes
Alexandre Meneghello Fuentefria
Marilene Henning Vainstein
Saulo Fernandes de Andrade
A Potent Fluorescent Derivative of 8-Hydroxyquinoline Suggests Cell Wall Damage as a Possible Cellular Action of the 5-Triazole 8-Hydroxyquinoline Class
Applied Microbiology
8-hydroxyquinoline
triazole
antifungal activity
cell wall action
fluorescence
microscopy
title A Potent Fluorescent Derivative of 8-Hydroxyquinoline Suggests Cell Wall Damage as a Possible Cellular Action of the 5-Triazole 8-Hydroxyquinoline Class
title_full A Potent Fluorescent Derivative of 8-Hydroxyquinoline Suggests Cell Wall Damage as a Possible Cellular Action of the 5-Triazole 8-Hydroxyquinoline Class
title_fullStr A Potent Fluorescent Derivative of 8-Hydroxyquinoline Suggests Cell Wall Damage as a Possible Cellular Action of the 5-Triazole 8-Hydroxyquinoline Class
title_full_unstemmed A Potent Fluorescent Derivative of 8-Hydroxyquinoline Suggests Cell Wall Damage as a Possible Cellular Action of the 5-Triazole 8-Hydroxyquinoline Class
title_short A Potent Fluorescent Derivative of 8-Hydroxyquinoline Suggests Cell Wall Damage as a Possible Cellular Action of the 5-Triazole 8-Hydroxyquinoline Class
title_sort potent fluorescent derivative of 8 hydroxyquinoline suggests cell wall damage as a possible cellular action of the 5 triazole 8 hydroxyquinoline class
topic 8-hydroxyquinoline
triazole
antifungal activity
cell wall action
fluorescence
microscopy
url https://www.mdpi.com/2673-8007/5/2/38
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