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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
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.
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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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