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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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.
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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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