Oxadiazolylthiazoles as novel and selective antifungal agents.
Eur J Med Chem. 2020 Jan 10;189:112046
Authors: Hagras M, Salama EA, Sayed AM, Abutaleb NS, Kotb A, Seleem MN, Mayhoub AS
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.
PMID: 31962263 [PubMed – as supplied by publisher]