Seven previously undescribed compounds, acrenoids A-G (1-7), along with two known compounds (8 and 9), were isolated from the culture of the deep-sea-derived fungus Acremonium sclerotigenum LW14. The structures of these compounds were characterized by a combination of spectroscopic studies, ECD calculations, and ECD experiments induced by Rh2(OCOCF3)4. Acrenoid A (1) features a distinctive 5/5/7 tricyclic ring framework. Moreover, all isolates were evaluated for their antifungal activities. Notably, compound 9 exhibited potent antifungal activity against drug-resistant Candida auris 12766, with a MIC of 4 μg/mL. In addition, compound 9 exhibited low hemolytic toxicity. The antifungal mechanism of compound 9 involves cell membrane disruption and intracellular ROS accumulation. In addition to these effects, it also inhibited biofilm formation in C. auris 12766. These findings highlight compound 9 as a promising antifungal candidate for treating C. auris.
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