New butanolide derivatives from the marine derived fungus Aspergillus terreus GZU-31-1 by chemical epigenetic manipulation

Chemical epigenetic manipulation of Aspergillus terreus GZU-31-1 led to the discovery of five butanolide derivatives (1-5), including two new ones (1 and 2), and four known diphenyl ether derivatives (6-9). Compound 1 featured a Z-configuration double bond in the isoprenyl group was a potential anti-inflammatory bioactive group. Compound 2 was a new natural product. Moreover, compound 3 with a deacetylated group at C-4 was rarely reported as a butanolide analogue, which was isolated from the liquid culture treated with polyketide pathway inhibitor sodium citrate dihydrate. All of the isolates (1-9) were tested for their anti-inflammatory effects on the production of nitric oxide in lipopolysaccharide-induced microglial cells (RAW 264.7 cells). Compounds 1, 7, 8 and 9 exhibited more potent anti-inflammatory activity with IC₅₀ values of 16.31, 20.16, 9.53 and 21.64 μM than the positive control (indomethacin, IC₅₀, 24.0 μM).