Anti-Epstein–Barr Viral Agents from the Medicinal Herb-Derived Fungus Alternaria alstroemeriae Km2286

Chromatographic separation on the liquid-state fermented products produced by the fungal strain Alternaria alstroemeriae Km2286 isolated from the littoral medicinal herb Atriplex maximowicziana Makino resulted in the isolation of compounds 1–9. Structures were determined by spectroscopic analysis as four undescribed perylenequinones, altertromins A–D (1–4), along with altertoxin IV (5), altertoxin VIII (6), stemphyperylenol (7), tenuazonic acid (8), and allo-tenuazonic acid (9). Compounds 1–6 exhibited antiviral activities against Epstein–Barr virus (EBV) with EC50 values ranging from 0.17 ± 0.07 to 3.13 ± 0.31 μM and selectivity indices higher than 10. In an anti-neuroinflammatory assay, compounds 1–4, 6, and 7 showed inhibitory activity of nitric oxide production in lipopolysaccharide-induced microglial BV-2 cells, with IC50 values ranging from 0.33 ± 0.04 to 4.08 ± 0.53 μM without significant cytotoxicity. This is the first report to describe perylenequinone-type compounds with potent anti-EBV and anti-neuroinflammatory activities.