Macrooxazoles A-D, New 2,5-Disubstituted Oxazole-4-Carboxylic Acid Derivatives from the Plant Pathogenic Fungus .

In our ongoing search for new bioactive fungal metabolites, four previously undescribed oxazole carboxylic acid derivatives (-) for which we proposed the trivial names macrooxazoles A-D together with two known tetramic acids (-) were isolated from the plant pathogenic fungus . Their structures were elucidated based on high-resolution mass spectrometry (HR-MS) and nuclear magnetic resonance (NMR) spectroscopy. The hitherto unclear structure of macrocidin Z () was also confirmed by its first total synthesis. The isolated compounds were evaluated for their antimicrobial activities against a panel of bacteria and fungi. Cytotoxic and anti-biofilm activities of the isolates are also reported herein. The new compound exhibited weak-to-moderate antimicrobial activity as well as the known macrocidins and . Only the mixture of compounds and (ratio 1:2) showed weak cytotoxic activity against the tested cancer cell lines with an IC of 23 µg/mL. Moreover, the new compounds and , as well as the known compounds and , interfered with the biofilm formation of , inhibiting 65%, 75%, 79%, and 76% of biofilm at 250 µg/mL, respectively. Compounds and also exhibited moderate activity against preformed biofilm with the highest inhibition percentage of 75% and 73% at 250 µg/mL, respectively.