Fig. 2: In vitro antifungal activity, mammalian cell cytotoxicity, and microsome stability of isoxazole 1.
From: Discovery and mechanism of a highly selective, antifungal acetyl-CoA synthetase inhibitor
A The minimum inhibitory concentration (MIC) of 1 against C. neoformans reference strain H99 and acl1∆ mutant strains in YPD, YNB + 2%acetate, and RPMI-MOPS buffer at 37 °C. The values were identical for three independent experiments performed in technical duplicate. B MIC values against C. albicans reference strain SC5314 and C. glabrata CBS138. Fractional inhibitor concentrations against H99 for fluconazole (C) and rapamycin (D). Growth in wells is indicated by tan fill, while empty wells indicate no growth. The wells with red fill indicate the fractional inhibitory concentration (FIC). E HepG2 cells were exposed to the indicated concentrations of isoxazole 1 for 24 h. The release of LDH into the medium was determined as described in “Methods” and normalized to detergent-induced lysis. Data are means of two independent experiments performed in technical triplicate with error bars indicating standard deviation. F Structures of isoxazole 1 and 2. G In vitro stability of isoxazole 1 in human and mouse liver microsomes. The times indicate t1/2 in minutes. H In vitro stability of isoxazole 2 in the presence and absence of pan-cytochrome inhibitor 1-amino-benzotriazole (ABT). Source data are provided as a Source data file.
