KI/NaBr-Induced Variable Halogenated DMOA-Derived Isodhilarane-Type Meroterpenoids with Anti-inflammatory Activities from Mangrove Endophytic Fungus Talaromyces sp. SCNU-F0041

Five new 3,5-Dimethylorsellinic acid (DMOA)-derived isodhilarane-type meroterpenoids, amestolknoids D-H (1-5), were isolated from the 3% KI or 3% NaBr-containing rice-solid fermentation culture of Talaromyces sp. SCNU-F0041. Their structures were comprehensively established by extensive spectroscopic analysis, electronic circular dichroism (ECD) comparison, and single-crystal X-ray diffraction analysis. Structurally, compounds 1 and 2 represent the first reported examples of iodinated DMOA meroterpenoids, and compounds 3 and 4 are the rare brominated isodhilarane-type meroterpenoids (IMs). Furthermore, amestolknoid D (1) represents the first reported IMs featuring an epoxy-bridge between C-4 and C-13 of the seven-membered ring B of IMs, thereby constructing unprecedented epoxy-bridged 6/6/5/6/5/6 hexacyclic ring system. Bioassay-disclosed compounds 1 and 4 showed significant inhibitory effects on NO production in LPS-stimulated RAW 264.7 macrophages with IC50 values of 9.2 and 4.5 μM, respectively, as well as downregulating classic pro-inflammatory cytokines TNF-α and IL-6.