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Nontoxic Cobalt(III) Schiff Base Complexes with Broad‐Spectrum Antifungal Activity
Resistance to currently available antifungal drugs has quietly been on the rise but overshadowed by the alarming spread of antibacterial resistance. There is a striking lack of attention to the threat of drug‐resistant fungal infections, with only a handful of new drugs currently in development. Giv...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855930/ https://www.ncbi.nlm.nih.gov/pubmed/33231906 http://dx.doi.org/10.1002/chem.202003545 |
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author | Frei, Angelo King, A. Paden Lowe, Gabrielle J. Cain, Amy K. Short, Francesca L. Dinh, Hue Elliott, Alysha G. Zuegg, Johannes Wilson, Justin J. Blaskovich, Mark A. T. |
author_facet | Frei, Angelo King, A. Paden Lowe, Gabrielle J. Cain, Amy K. Short, Francesca L. Dinh, Hue Elliott, Alysha G. Zuegg, Johannes Wilson, Justin J. Blaskovich, Mark A. T. |
author_sort | Frei, Angelo |
collection | PubMed |
description | Resistance to currently available antifungal drugs has quietly been on the rise but overshadowed by the alarming spread of antibacterial resistance. There is a striking lack of attention to the threat of drug‐resistant fungal infections, with only a handful of new drugs currently in development. Given that metal complexes have proven to be useful new chemotypes in the fight against diseases such as cancer, malaria, and bacterial infections, it is reasonable to explore their possible utility in treating fungal infections. Herein we report a series of cobalt(III) Schiff base complexes with broad‐spectrum antifungal activity. Some of these complexes show minimum inhibitory concentrations (MIC) in the low micro‐ to nanomolar range against a series of Candida and Cryptococcus yeasts. Additionally, we demonstrate that these compounds show no cytotoxicity against both bacterial and human cells. Finally, we report the first in vivo toxicity data on these compounds in Galleria mellonella, showing that doses as high as 266 mg kg(−1) are tolerated without adverse effects, paving the way for further in vivo studies of these complexes. |
format | Online Article Text |
id | pubmed-7855930 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78559302021-03-02 Nontoxic Cobalt(III) Schiff Base Complexes with Broad‐Spectrum Antifungal Activity Frei, Angelo King, A. Paden Lowe, Gabrielle J. Cain, Amy K. Short, Francesca L. Dinh, Hue Elliott, Alysha G. Zuegg, Johannes Wilson, Justin J. Blaskovich, Mark A. T. Chemistry Full Papers Resistance to currently available antifungal drugs has quietly been on the rise but overshadowed by the alarming spread of antibacterial resistance. There is a striking lack of attention to the threat of drug‐resistant fungal infections, with only a handful of new drugs currently in development. Given that metal complexes have proven to be useful new chemotypes in the fight against diseases such as cancer, malaria, and bacterial infections, it is reasonable to explore their possible utility in treating fungal infections. Herein we report a series of cobalt(III) Schiff base complexes with broad‐spectrum antifungal activity. Some of these complexes show minimum inhibitory concentrations (MIC) in the low micro‐ to nanomolar range against a series of Candida and Cryptococcus yeasts. Additionally, we demonstrate that these compounds show no cytotoxicity against both bacterial and human cells. Finally, we report the first in vivo toxicity data on these compounds in Galleria mellonella, showing that doses as high as 266 mg kg(−1) are tolerated without adverse effects, paving the way for further in vivo studies of these complexes. John Wiley and Sons Inc. 2020-11-24 2021-01-26 /pmc/articles/PMC7855930/ /pubmed/33231906 http://dx.doi.org/10.1002/chem.202003545 Text en © 2020 The Authors. Published by Wiley-VCH GmbH This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Full Papers Frei, Angelo King, A. Paden Lowe, Gabrielle J. Cain, Amy K. Short, Francesca L. Dinh, Hue Elliott, Alysha G. Zuegg, Johannes Wilson, Justin J. Blaskovich, Mark A. T. Nontoxic Cobalt(III) Schiff Base Complexes with Broad‐Spectrum Antifungal Activity |
title | Nontoxic Cobalt(III) Schiff Base Complexes with Broad‐Spectrum Antifungal Activity |
title_full | Nontoxic Cobalt(III) Schiff Base Complexes with Broad‐Spectrum Antifungal Activity |
title_fullStr | Nontoxic Cobalt(III) Schiff Base Complexes with Broad‐Spectrum Antifungal Activity |
title_full_unstemmed | Nontoxic Cobalt(III) Schiff Base Complexes with Broad‐Spectrum Antifungal Activity |
title_short | Nontoxic Cobalt(III) Schiff Base Complexes with Broad‐Spectrum Antifungal Activity |
title_sort | nontoxic cobalt(iii) schiff base complexes with broad‐spectrum antifungal activity |
topic | Full Papers |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855930/ https://www.ncbi.nlm.nih.gov/pubmed/33231906 http://dx.doi.org/10.1002/chem.202003545 |
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