Hexacyclic 6/6/6/5/6/6 Spirosteroids Produced by a Marine-Derived Fungus <i>Galactomyces pseudocandidus</i> and Antifungal Activity against <i>Candida</i> Species

Two spirosteroids, epoformsterols A and B (<b>1</b> and <b>2</b>), featuring a highly fused 6/6/6/5/6/6 hexacyclic framework, were isolated from the marine-derived fungus <i>Galactomyces pseudocandidus</i>. The structures of <b>1</b> and <b>2</b> were elucidated by NMR, HRMS, and single-crystal X-ray diffraction. The absolute configuration of <b>1</b> was established by comparison of calculated and experimental ECD spectra, and that of <b>2</b> was assigned by ECD comparison with <b>1</b>. Compounds <b>1</b> and <b>2</b> exhibited inhibitory activity against <i>Candida auris</i> and <i>C. albicans</i> with MIC values of 3.12-12.5 μg/mL, and MFC/MIC ratios suggested a fungistatic mode of action. Both compounds also inhibited <i>C. rugosa</i> lipase (CRL) in a model enzyme assay, with IC₅₀ values of 5.7 and 8.9 μM, respectively. These results identify a distinctive class of fungal steroids with antifungal activity.