Stereochemical Characterization of Bis-Indolyl Alkaloids from the Marine Fungus Aspergillus ochraceopetaliformis FM451 and Their Differential Effects on Candida albicans

Marine-derived fungi are a rich source of structurally diverse secondary metabolites with unique biological activities. Guided by an integrated GNPS molecular networking strategy, chemical investigation of the culture extract of the marine-derived fungus Aspergillus ochraceopetaliformis FM451 led to the isolation of four bis-indolyl alkaloids (1–4). Their structures were elucidated as asterriquinol G (1), asterriquinone K (2), asterriquinone C-1 (3), and asterriquinol E (4) based on comprehensive NMR spectroscopic analyses and HRESIMS data. The enantiomers of asterriquinol G (1a and 1b) were further separated by semi-preparative chiral HPLC, and their absolute configurations were assigned by comparison of the experimental and calculated specific rotations. In addition, the absolute configuration of asterriquinone K (2) was assigned as 11″R based on its specific rotation. Although the planar structures of compounds 1 and 2 had previously been reported, 11″R-asterriquinol G (1a), 11″S-asterriquinol G (1b), and 11″R-asterriquinone K (2) represent the first complete stereochemical characterization of these bis-indolyl alkaloids. All isolated compounds were evaluated for their effects on the growth and biofilm-associated phenotypes of Candida albicans. Although their effects on fungal growth were limited, compound 1a produced the greatest reduction in surface-associated biofilm biomass among the tested compounds, reducing crystal violet-stained biomass to approximately 50% of the control level at 16 μg/mL. Its enantiomer 1b was associated with more pronounced alterations in residual biofilm morphology, with fewer apparent hyphal structures than those observed following treatment with 1a at comparable concentrations. These findings provide preliminary evidence that the stereochemistry of asterriquinol G may differentially influence its biofilm-associated effects on C. albicans and provide a basis for further stereochemistry-oriented studies of bis-indolyl alkaloids from A. ochraceopetaliformis FM451.