Anti-inflammatory and anti-proliferative cyclodepsipeptides from an endophytic fungus Fusarium iranicum YH6.

The genus Fusarium is a prolific producer of chemically diverse natural products that exhibit a broad spectrum of biological activities, including antibacterial, insecticidal, and anticancer effects. In this study, bioassay-guided isolation from an endophytic fungus Fusarium iranicum YH6 led to the discovery of four previously undescribed cyclodepsipeptides, fusaristatins I-L (1-4), along with a known analogue fusaristatin A (5). Their planar structures were elucidated on the basis of 1D and 2D NMR, and HR ESI-MS spectroscopic analyses. The relative and absolute configurations were rigorously assigned using advanced Marfey's method, J-based configuration analysis, and DP4+ probability assessments. The biological activities of all isolated cyclodepsipeptides were evaluated, including anti-inflammatory activity in LPS-induced RAW264.7 macrophage cells, anti-proliferative activity against A549 and HCC827 cell lines, and antibacterial activity against Staphylococcus aureus. Compounds 1-5 exhibited potent anti-inflammatory activities by inhibiting NO production in LPS-stimulated RAW264.7 macrophages, with IC50 values ranging from 5.7 to 20.5 μM. Fusaristatin K (3) (IC50: 5.7 μM) displayed the most significant inhibition and down-regulated the expression of the TLR4/NF-κB/NLRP3 signaling pathway to exert the anti-inflammatory activity.