Chartarlactams U-X: Novel Phenylspirodrimanes from a Marine Derived Fungus Stachybotrys sp. SZU-W23 with Anti-Inflammatory Activity Mediated by the NF-κB/ROS Signaling Pathways.

In this investigation, the anti-inflammatory potential of phenylspirodrimanes (PSDs) produced by the marine-derived fungal strain Stachybotrys sp. SZU-W23 was systematically explored. A total of 15 PSDs were successfully isolated. Among them, four novel compounds, designated as chartarlactams U-X, were precisely characterized using NMR, HRESIMS, and ECD analyses. Specifically, compound 10 exhibited the most potent inhibitory effect on nitric oxide production in LPS-stimulated RAW 264.7 macrophages within the 0.3-30 μM concentration range, with an IC50 value of 12.4 μM. Additionally, MTT assays revealed no detectable cytotoxicity at these concentrations. Mechanistic studies revealed that compound 10 effectively suppressed ROS generation, likely inactivating the NF-κB signaling pathway and consequently downregulating pro-inflammatory mediators, including iNOS, IL-6, and IL-1β.