Trichopsistides A and B: Two Highly Oxygenated Pentacyclic Polyketides with Promising Inhibitory Effects on the NF-κB Signaling Pathway from the Fungus Trichoderma koningiopsisWZ-196

Two highly oxygenated pentacyclic polyketides with two new carbon skeletons, trichopsistide A (1) and trichopsistide B (2), were isolated from the plant endophyte Trichoderma koningiopsisWZ-196 derived from the leaf of Rubia podanthaDiels. The structures of these polyketides with full configurations were determined by comprehensive spectroscopic analysis, computer-assisted structure elucidation software, computational calculation, and X-ray crystal diffraction. Among them, 1represented the first example of an unprecedented 5/6/6/6/5 pentacyclic ketal-containing polyketide pyridine alkaloid, and 2possessed a novel 6/6/6/6/5 pentacyclic ketal-containing polyketide scaffold fused with an α-pyrone. The plausible biosynthetic route for 1and 2was also proposed. Moreover, biological activity assays showed that 1and 2possessed inhibitory effects on the NF-κB signaling pathway with IC50values of 14.77 and 8.58 μM, respectively. Furthermore, 1and 2could also inhibit the expression of IκBα and p65 phosphorylation, decrease the expression of MCP-1, E-selectin, and IL-8at the mRNA level, and inhibit the TNF-α-induced nuclear translocation of p65.