Oxadiazolylthiazoles as novel and selective antifungal agents.
Antifungal
Candida auris
Cryptococcal infections
Fluconazole-resistant Candida spp
Journal
European journal of medicinal chemistry
ISSN: 1768-3254
Titre abrégé: Eur J Med Chem
Pays: France
ID NLM: 0420510
Informations de publication
Date de publication:
01 Mar 2020
01 Mar 2020
Historique:
received:
13
10
2019
revised:
20
12
2019
accepted:
06
01
2020
pubmed:
22
1
2020
medline:
17
7
2020
entrez:
22
1
2020
Statut:
ppublish
Résumé
Studying the structure-activity relationships (SAR) of oxadiazolylthiazole antibiotics unexpectedly led us to identify ethylenediamine- and propylenediamine-analogs as potential antimycotic novel lead structures. Replacement of the ethylenediamine moiety for the lead compound 7 with cis-diaminocyclohexyl group (compound 18) significantly enhanced the antifungal activity. In addition to the high safety margin of 18 against mammalian cells, it showed highly selective broad-spectrum activity against fungal cells without inhibiting the human normal microbiota. The antifungal activity of 18 was investigated against 20 drug-resistant clinically important fungi, including Candida species, Cryptococcus, and Aspergillus fumigatus strains. In addition to the low MIC values that mostly ranged between 0.125 and 2.0 μg/mL, compound 18 outperformed fluconazole in disrupting mature Candida biofilm.
Identifiants
pubmed: 31962263
pii: S0223-5234(20)30013-1
doi: 10.1016/j.ejmech.2020.112046
pii:
doi:
Substances chimiques
Antifungal Agents
0
Oxadiazoles
0
Thiazoles
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
112046Informations de copyright
Copyright © 2020 Elsevier Masson SAS. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest There are no conflicts to declare.