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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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) |
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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 |
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