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 IC 50 values of 16.31, 20.16, 9.53 and 21.64 μM than the positive control (indomethacin, IC 50 , 24.0 μM).