Nucleobase-Coupled Xanthones with Anti-ROS Effects from Marine-Derived Fungus Aspergillus sydowii .

A MS/MS-based molecular networking approach compared to the Global Natural Product Social Molecular Networking library, in association with genomic annotation of natural product biosynthetic gene clusters within a marine-derived fungus, Aspergillus sydowii , identified a suite of xanthone metabolites. Chromatographic techniques applied to the cultured fungus led to the isolation of 11 xanthone-based alkaloids, dubbed sydoxanthones F-M. The structures of these alkaloids were elucidated using extensive spectroscopic data, including electronic circular dichroism and single-crystal X-ray diffraction data for configurational assignments. Among these analogues, sydoxanthones F-K exhibit structure features typical of nucleobase-coupled xanthones, with sydoxanthone H being an N -bonded xanthone dimer. Notably, (±)sydoxanthones F ( 1a / 1b ), (±)sydoxanthones H ( 3b / 3a ), and (±)sydoxanthones J ( 5b / 5a ) are enantiomeric pairs, while sydoxanthones G ( 2 ), I ( 4 ), and K ( 6 ) are stereoisomers of 1 , 3 , and 5 , respectively. Furthermore, (+)sydoxanthone H ( 3a ) demonstrated significant rescue of cell viability in H 2 O 2 -injuried SH-SY5Y cells by inhibiting reactive oxygen species production, suggesting its potential for neuroprotection.