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 EC 50 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 IC 50 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.