Trichopsistides A and B: Two Highly Oxygenated Pentacyclic Polyketides with Promising Inhibitory Effects on the NF-κB Signaling Pathway from the Fungus Trichoderma koningiopsis WZ-196.
Li FengAn-Xin ZhangRan-Ran ShangXin-Jia WangNing-Hua TanZhe WangPublished in: The Journal of organic chemistry (2022)
Two highly oxygenated pentacyclic polyketides with two new carbon skeletons, trichopsistide A ( 1 ) and trichopsistide B ( 2 ), were isolated from the plant endophyte Trichoderma koningiopsis WZ-196 derived from the leaf of Rubia podantha Diels. 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, 1 represented the first example of an unprecedented 5/6/6/6/5 pentacyclic ketal-containing polyketide pyridine alkaloid, and 2 possessed a novel 6/6/6/6/5 pentacyclic ketal-containing polyketide scaffold fused with an α-pyrone. The plausible biosynthetic route for 1 and 2 was also proposed. Moreover, biological activity assays showed that 1 and 2 possessed inhibitory effects on the NF-κB signaling pathway with IC 50 values of 14.77 and 8.58 μM, respectively. Furthermore, 1 and 2 could also inhibit the expression of IκBα and p65 phosphorylation, decrease the expression of MCP-1 , E-selectin , and IL-8 at the mRNA level, and inhibit the TNF-α-induced nuclear translocation of p65.
Keyphrases
- signaling pathway
- pi k akt
- poor prognosis
- induced apoptosis
- epithelial mesenchymal transition
- binding protein
- high resolution
- rheumatoid arthritis
- nuclear factor
- oxidative stress
- high glucose
- electron microscopy
- inflammatory response
- magnetic resonance
- drug induced
- mass spectrometry
- molecular dynamics simulations
- endoplasmic reticulum stress
- computed tomography
- monte carlo
- single cell