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...

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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:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c32c17df284e4424a4ae463cb4b0531e
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spelling	oai:doaj.org-article:c32c17df284e4424a4ae463cb4b0531e2021-11-11T07:14:42ZEvaluation of bisphenylthiazoles as a promising class for combating multidrug-resistant fungal infections1932-6203https://doaj.org/article/c32c17df284e4424a4ae463cb4b0531e2021-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8568133/?tool=EBIhttps://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 (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/c32c17df284e4424a4ae463cb4b0531e
work_keys_str_mv	AT mohamedhagras evaluationofbisphenylthiazolesasapromisingclassforcombatingmultidrugresistantfungalinfections AT nadersabutaleb evaluationofbisphenylthiazolesasapromisingclassforcombatingmultidrugresistantfungalinfections AT ahmedmsayed evaluationofbisphenylthiazolesasapromisingclassforcombatingmultidrugresistantfungalinfections AT ehabasalama evaluationofbisphenylthiazolesasapromisingclassforcombatingmultidrugresistantfungalinfections AT mohamednseleem evaluationofbisphenylthiazolesasapromisingclassforcombatingmultidrugresistantfungalinfections AT abdelrahmansmayhoub evaluationofbisphenylthiazolesasapromisingclassforcombatingmultidrugresistantfungalinfections
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Evaluation of bisphenylthiazoles as a promising class for combating multidrug-resistant fungal infections

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