Evaluation of bisphenylthiazoles as a promising class for combating multidrug-resistant fungal infections.

To minimize the intrinsic toxicity of the antibacterial agent hydrazinyloxadiazole 1, the hydrazine moiety was replaced with ethylenediamine (compound 7). This replacement generated a potent antifungal agent with no antibacterial activity. Notably, use of a 1,2-diaminocyclohexane moiety, as a confor...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Mohamed Hagras, Nader S Abutaleb, Ahmed M Sayed, Ehab A Salama, Mohamed N Seleem, Abdelrahman S Mayhoub
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2021
Materias:
R
Q
Acceso en línea:https://doaj.org/article/ffc5e06893d34d8db43eed9dd9983c27
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:ffc5e06893d34d8db43eed9dd9983c27
record_format dspace
spelling oai:doaj.org-article:ffc5e06893d34d8db43eed9dd9983c272021-12-02T20:04:24ZEvaluation of bisphenylthiazoles as a promising class for combating multidrug-resistant fungal infections.1932-620310.1371/journal.pone.0258465https://doaj.org/article/ffc5e06893d34d8db43eed9dd9983c272021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0258465https://doaj.org/toc/1932-6203To minimize the intrinsic toxicity of the antibacterial agent hydrazinyloxadiazole 1, the hydrazine moiety was replaced with ethylenediamine (compound 7). This replacement generated a potent antifungal agent with no antibacterial activity. Notably, use of a 1,2-diaminocyclohexane moiety, as a conformationally-restricted isostere for ethylenediamine, potentiated the antifungal activity in both the cis and trans forms of N-(5-(2-([1,1'-biphenyl]-4-yl)-4-methylthiazol-5-yl)-1,3,4-oxadiazol-2-yl)cyclohexane-1,2-diamine (compounds 16 and 17). Both compounds 16 and 17 were void of any antibacterial activity; nonetheless, they showed equipotent antifungal activity in vitro to that of the most potent approved antifungal agent, amphotericin B. The promising antifungal effects of compounds 16 and 17 were maintained when assessed against an additional panel of 26 yeast and mold clinical isolates, including the Candida auris and C. krusei. Furthermore, compound 17 showed superior activity to amphotericin B in vitro against Candida glabrata and Cryptococcus gattii. Additionally, neither compound inhibited the normal human microbiota, and both possessed excellent safety profiles and were 16 times more tolerable than amphotericin B.Mohamed HagrasNader S AbutalebAhmed M SayedEhab A SalamaMohamed N SeleemAbdelrahman S MayhoubPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 11, p e0258465 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Mohamed Hagras
Nader S Abutaleb
Ahmed M Sayed
Ehab A Salama
Mohamed N Seleem
Abdelrahman S Mayhoub
Evaluation of bisphenylthiazoles as a promising class for combating multidrug-resistant fungal infections.
description To minimize the intrinsic toxicity of the antibacterial agent hydrazinyloxadiazole 1, the hydrazine moiety was replaced with ethylenediamine (compound 7). This replacement generated a potent antifungal agent with no antibacterial activity. Notably, use of a 1,2-diaminocyclohexane moiety, as a conformationally-restricted isostere for ethylenediamine, potentiated the antifungal activity in both the cis and trans forms of N-(5-(2-([1,1'-biphenyl]-4-yl)-4-methylthiazol-5-yl)-1,3,4-oxadiazol-2-yl)cyclohexane-1,2-diamine (compounds 16 and 17). Both compounds 16 and 17 were void of any antibacterial activity; nonetheless, they showed equipotent antifungal activity in vitro to that of the most potent approved antifungal agent, amphotericin B. The promising antifungal effects of compounds 16 and 17 were maintained when assessed against an additional panel of 26 yeast and mold clinical isolates, including the Candida auris and C. krusei. Furthermore, compound 17 showed superior activity to amphotericin B in vitro against Candida glabrata and Cryptococcus gattii. Additionally, neither compound inhibited the normal human microbiota, and both possessed excellent safety profiles and were 16 times more tolerable than amphotericin B.
format article
author Mohamed Hagras
Nader S Abutaleb
Ahmed M Sayed
Ehab A Salama
Mohamed N Seleem
Abdelrahman S Mayhoub
author_facet Mohamed Hagras
Nader S Abutaleb
Ahmed M Sayed
Ehab A Salama
Mohamed N Seleem
Abdelrahman S Mayhoub
author_sort Mohamed Hagras
title Evaluation of bisphenylthiazoles as a promising class for combating multidrug-resistant fungal infections.
title_short Evaluation of bisphenylthiazoles as a promising class for combating multidrug-resistant fungal infections.
title_full Evaluation of bisphenylthiazoles as a promising class for combating multidrug-resistant fungal infections.
title_fullStr Evaluation of bisphenylthiazoles as a promising class for combating multidrug-resistant fungal infections.
title_full_unstemmed Evaluation of bisphenylthiazoles as a promising class for combating multidrug-resistant fungal infections.
title_sort evaluation of bisphenylthiazoles as a promising class for combating multidrug-resistant fungal infections.
publisher Public Library of Science (PLoS)
publishDate 2021
url https://doaj.org/article/ffc5e06893d34d8db43eed9dd9983c27
work_keys_str_mv AT mohamedhagras evaluationofbisphenylthiazolesasapromisingclassforcombatingmultidrugresistantfungalinfections
AT nadersabutaleb evaluationofbisphenylthiazolesasapromisingclassforcombatingmultidrugresistantfungalinfections
AT ahmedmsayed evaluationofbisphenylthiazolesasapromisingclassforcombatingmultidrugresistantfungalinfections
AT ehabasalama evaluationofbisphenylthiazolesasapromisingclassforcombatingmultidrugresistantfungalinfections
AT mohamednseleem evaluationofbisphenylthiazolesasapromisingclassforcombatingmultidrugresistantfungalinfections
AT abdelrahmansmayhoub evaluationofbisphenylthiazolesasapromisingclassforcombatingmultidrugresistantfungalinfections
_version_ 1718375641828556800