Anti-inflammatory polyketides from the endophytic fungus Cladosporium pseudocladosporioides A887

Abstract

Six undescribed tetralone derivatives, cladosporids A-C (1–3) and cladosporols K-M (4–6), together with eleven known cladosporols (7–17), were obtained from the endophytic fungus Cladosporium pseudocladosporioides A887, which was derived from Aquilaria sinensis (Lour.) Gilg. Specially, cladosporids A-C featured a previously undescribed skeleton with a fascinated 6/6/6/6/6-fused pentacyclic system, wherein cladosporids B and C were a pair of epimers. The structures and absolute configurations of these unreported compounds were determined using 1D/2D NMR, HRESIMS, UV, IR, ECD and quantum chemical calculations. In the bioassay, compounds 10, 11, 15, and 17 exhibited significant inhibitory effects on lipopolysaccharide induced nitric oxide production in RAW 264.7 macrophage cells with IC₅₀ values ranging from 3.81 to 21.59 μM. To explore the binding interactions of the unreported derivatives (1–3) with their targets, molecular docking analysis was conducted against inducible nitric oxide synthase, revealing potential binding affinities and modes. Additionally, their plausible biosynthetic pathways were also discussed.