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Augmenting Azoles with Drug Synergy to Expand the Antifungal Toolbox

Fungal infections impact the lives of at least 12 million people every year, killing over 1.5 million. Wide-spread use of fungicides and prophylactic antifungal therapy have driven resistance in many serious fungal pathogens, and there is an urgent need to expand the current antifungal arsenal. Rece...

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Detalles Bibliográficos
Autores principales: Kane, Aidan, Carter, Dee A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9027798/
https://www.ncbi.nlm.nih.gov/pubmed/35455479
http://dx.doi.org/10.3390/ph15040482
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author Kane, Aidan
Carter, Dee A.
author_facet Kane, Aidan
Carter, Dee A.
author_sort Kane, Aidan
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description Fungal infections impact the lives of at least 12 million people every year, killing over 1.5 million. Wide-spread use of fungicides and prophylactic antifungal therapy have driven resistance in many serious fungal pathogens, and there is an urgent need to expand the current antifungal arsenal. Recent research has focused on improving azoles, our most successful class of antifungals, by looking for synergistic interactions with secondary compounds. Synergists can co-operate with azoles by targeting steps in related pathways, or they may act on mechanisms related to resistance such as active efflux or on totally disparate pathways or processes. A variety of sources of potential synergists have been explored, including pre-existing antimicrobials, pharmaceuticals approved for other uses, bioactive natural compounds and phytochemicals, and novel synthetic compounds. Synergy can successfully widen the antifungal spectrum, decrease inhibitory dosages, reduce toxicity, and prevent the development of resistance. This review highlights the diversity of mechanisms that have been exploited for the purposes of azole synergy and demonstrates that synergy remains a promising approach for meeting the urgent need for novel antifungal strategies.
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spelling pubmed-90277982022-04-23 Augmenting Azoles with Drug Synergy to Expand the Antifungal Toolbox Kane, Aidan Carter, Dee A. Pharmaceuticals (Basel) Review Fungal infections impact the lives of at least 12 million people every year, killing over 1.5 million. Wide-spread use of fungicides and prophylactic antifungal therapy have driven resistance in many serious fungal pathogens, and there is an urgent need to expand the current antifungal arsenal. Recent research has focused on improving azoles, our most successful class of antifungals, by looking for synergistic interactions with secondary compounds. Synergists can co-operate with azoles by targeting steps in related pathways, or they may act on mechanisms related to resistance such as active efflux or on totally disparate pathways or processes. A variety of sources of potential synergists have been explored, including pre-existing antimicrobials, pharmaceuticals approved for other uses, bioactive natural compounds and phytochemicals, and novel synthetic compounds. Synergy can successfully widen the antifungal spectrum, decrease inhibitory dosages, reduce toxicity, and prevent the development of resistance. This review highlights the diversity of mechanisms that have been exploited for the purposes of azole synergy and demonstrates that synergy remains a promising approach for meeting the urgent need for novel antifungal strategies. MDPI 2022-04-14 /pmc/articles/PMC9027798/ /pubmed/35455479 http://dx.doi.org/10.3390/ph15040482 Text en © 2022 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 Review
Kane, Aidan
Carter, Dee A.
Augmenting Azoles with Drug Synergy to Expand the Antifungal Toolbox
title Augmenting Azoles with Drug Synergy to Expand the Antifungal Toolbox
title_full Augmenting Azoles with Drug Synergy to Expand the Antifungal Toolbox
title_fullStr Augmenting Azoles with Drug Synergy to Expand the Antifungal Toolbox
title_full_unstemmed Augmenting Azoles with Drug Synergy to Expand the Antifungal Toolbox
title_short Augmenting Azoles with Drug Synergy to Expand the Antifungal Toolbox
title_sort augmenting azoles with drug synergy to expand the antifungal toolbox
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9027798/
https://www.ncbi.nlm.nih.gov/pubmed/35455479
http://dx.doi.org/10.3390/ph15040482
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