An Unusual Spiro-Fused Indole Alkaloid-Terrein Hybrid From Marine-Derived Fungus Aspergillus chevalieri HK-56.

One previously undescribed alkaloid variecoterrein (1) and seven known compounds (2-8) were obtained from the solid-state fermentation culture of the marine-derived fungus Aspergillus chevalieri HK-56. The planar and stereochemical structures of 1 was unambiguously elucidated by comprehensive spectroscopic analysis, including 1D and 2D nuclear magnetic resonance (NMR) spectroscopy, high-resolution electrospray ionization mass spectrometry (HRESIMS), DP4+ probability analysis, and electronic circular dichroism (ECD) spectroscopy. Compound 1 represents a structurally unique hybrid molecule, constituting the first naturally occurring conjugate that incorporates both indole 2,5-diketopiperazine alkaloid and terrein structural scaffolds. All isolated compounds were evaluated for their inhibitory effects on nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW 264.7 murine macrophage cells. Among them, compound 2 exhibited potent in vitro anti-inflammatory activity, with an IC50 value of 22.72 ± 0.22 µM, comparable to the positive control quercetin (IC50 = 13.81 ± 0.35 µM).