Undescribed phenylspirodrimane dimers with anti-gouty activity from the coral-derived fungus Stachybotrys chartarum

Nine previously undescribed phenylspirodrimane dimers, distachydrimanes G-O (1-6 and 8-10), along with one known analogue (7), were isolated from the fermentation culture of the coral-derived endophytic fungus Stachybotrys chartarum. Their structures were elucidated through comprehensive spectroscopic analyses, including NMR and HRESIMS, comparison of experimental and calculated ECD data, and single-crystal X-ray diffraction analysis. Compounds 1-6 comprise three isomeric pairs linked via a 6/7-membered oxygen heterocycle. Compounds 2, 4, and 6 possess the first-reported 22S,23R,23'R configuration, whereas compounds 1, 3, and 5 feature the rare 22R,23S,23'S configuration. Compound 10 represents the first C-18-C-23'-linked dimer with a furan-deficient monomer. Bioactivity assays demonstrated that compound 3 potently inhibited MSU-induced IL-1β secretion and pseudopodia formation in THP-1 cells. It attenuated oxidative stress by suppressing ROS generation, thereby blocking NF-κB p65 nuclear translocation and subsequent cascade of inflammatory responses, cellular senescence, and DNA damage. These findings highlight compound 3 as a promising lead for anti-gouty arthritis therapeutics.