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Antifungal Activity of an Original Amino-Isocyanonaphthalene (ICAN) Compound Family: Promising Broad Spectrum Antifungals
Multiple drug resistant fungi pose a serious threat to human health, therefore the development of completely new antimycotics is of paramount importance. The in vitro antifungal activity of the original, 1-amino-5-isocyanonaphthalenes (ICANs) was evaluated against reference strains of clinically imp...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7070524/ https://www.ncbi.nlm.nih.gov/pubmed/32085460 http://dx.doi.org/10.3390/molecules25040903 |
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author | Nagy, Miklós Szemán-Nagy, Gábor Kiss, Alexandra Nagy, Zsolt László Tálas, László Rácz, Dávid Majoros, László Tóth, Zoltán Szigeti, Zsuzsa Máthéné Pócsi, István Kéki, Sándor |
author_facet | Nagy, Miklós Szemán-Nagy, Gábor Kiss, Alexandra Nagy, Zsolt László Tálas, László Rácz, Dávid Majoros, László Tóth, Zoltán Szigeti, Zsuzsa Máthéné Pócsi, István Kéki, Sándor |
author_sort | Nagy, Miklós |
collection | PubMed |
description | Multiple drug resistant fungi pose a serious threat to human health, therefore the development of completely new antimycotics is of paramount importance. The in vitro antifungal activity of the original, 1-amino-5-isocyanonaphthalenes (ICANs) was evaluated against reference strains of clinically important Candida species. Structure-activity studies revealed that the naphthalene core and the isocyano- together with the amino moieties are all necessary to exert antifungal activity. 1,1-N-dimethylamino-5-isocyanonaphthalene (DIMICAN), the most promising candidate, was tested further in vitro against clinical isolates of Candida species, yielding a minimum inhibitory concentration (MIC) of 0.04–1.25 µg/mL. DIMICAN was found to be effective against intrinsically fluconazole resistant Candida krusei isolates, too. In vivo experiments were performed in a severly neutropenic murine model inoculated with a clinical strain of Candida albicans. Daily administration of 5 mg/kg DIMICAN intraperitoneally resulted in 80% survival even at day 13, whereas 100% of the control group died within six days. Based on these results, ICANs may become an effective clinical lead compound family against fungal pathogens. |
format | Online Article Text |
id | pubmed-7070524 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-70705242020-03-19 Antifungal Activity of an Original Amino-Isocyanonaphthalene (ICAN) Compound Family: Promising Broad Spectrum Antifungals Nagy, Miklós Szemán-Nagy, Gábor Kiss, Alexandra Nagy, Zsolt László Tálas, László Rácz, Dávid Majoros, László Tóth, Zoltán Szigeti, Zsuzsa Máthéné Pócsi, István Kéki, Sándor Molecules Article Multiple drug resistant fungi pose a serious threat to human health, therefore the development of completely new antimycotics is of paramount importance. The in vitro antifungal activity of the original, 1-amino-5-isocyanonaphthalenes (ICANs) was evaluated against reference strains of clinically important Candida species. Structure-activity studies revealed that the naphthalene core and the isocyano- together with the amino moieties are all necessary to exert antifungal activity. 1,1-N-dimethylamino-5-isocyanonaphthalene (DIMICAN), the most promising candidate, was tested further in vitro against clinical isolates of Candida species, yielding a minimum inhibitory concentration (MIC) of 0.04–1.25 µg/mL. DIMICAN was found to be effective against intrinsically fluconazole resistant Candida krusei isolates, too. In vivo experiments were performed in a severly neutropenic murine model inoculated with a clinical strain of Candida albicans. Daily administration of 5 mg/kg DIMICAN intraperitoneally resulted in 80% survival even at day 13, whereas 100% of the control group died within six days. Based on these results, ICANs may become an effective clinical lead compound family against fungal pathogens. MDPI 2020-02-18 /pmc/articles/PMC7070524/ /pubmed/32085460 http://dx.doi.org/10.3390/molecules25040903 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Nagy, Miklós Szemán-Nagy, Gábor Kiss, Alexandra Nagy, Zsolt László Tálas, László Rácz, Dávid Majoros, László Tóth, Zoltán Szigeti, Zsuzsa Máthéné Pócsi, István Kéki, Sándor Antifungal Activity of an Original Amino-Isocyanonaphthalene (ICAN) Compound Family: Promising Broad Spectrum Antifungals |
title | Antifungal Activity of an Original Amino-Isocyanonaphthalene (ICAN) Compound Family: Promising Broad Spectrum Antifungals |
title_full | Antifungal Activity of an Original Amino-Isocyanonaphthalene (ICAN) Compound Family: Promising Broad Spectrum Antifungals |
title_fullStr | Antifungal Activity of an Original Amino-Isocyanonaphthalene (ICAN) Compound Family: Promising Broad Spectrum Antifungals |
title_full_unstemmed | Antifungal Activity of an Original Amino-Isocyanonaphthalene (ICAN) Compound Family: Promising Broad Spectrum Antifungals |
title_short | Antifungal Activity of an Original Amino-Isocyanonaphthalene (ICAN) Compound Family: Promising Broad Spectrum Antifungals |
title_sort | antifungal activity of an original amino-isocyanonaphthalene (ican) compound family: promising broad spectrum antifungals |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7070524/ https://www.ncbi.nlm.nih.gov/pubmed/32085460 http://dx.doi.org/10.3390/molecules25040903 |
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