Diketopiperazine and diphenylether derivatives from marine algae-derived aspergillus versicolor OUCMDZ-2738 by epigenetic activation

Abstract

A chemical-epigenetic method was used to enhance the chemodiversity of a marine algicolous fungus. Apart from thirteen known compounds, (+)-brevianamide R ((+)-3), (-)-brevianamide R ((-)-3), (+)-brevianamide Q ((+)-4), (-)-brevianamide Q ((-)-4), brevianamide V ((+)-5), brevianamide W ((-)-5), brevianamide K (6), diorcinol B (7), diorcinol C (8), diorcinol E (9), diorcinol J (10), diorcinol (11), 4-methoxycarbonyldiorcinol (12), two new compounds, (+)- and (-)-brevianamide X ((+)- and (-)- 2)), as well as a new naturally occurring one, 3-[6-(2-methylpropyl)-2-oxo-1H-pyrazin-3-yl]propanamide (1), were isolated from chemical-epigenetic cultures of Aspergillus versicolor OUCMDZ-2738 with 10 µM vorinostat (SAHA). Compared to cultures in the same medium without SAHA, compounds 1–4, 8, 9, 11, and 12 were solely observed under SAHA condition. The structures of these compounds were elucidated based on spectroscopic analysis, specific rotation analysis, ECD, and X-ray crystallographic analysis. (±)-3, (±)-4, and (±)-5 were further resolved into the corresponding optically pure enantiomers and their absolute configurations were determined for the first time. Compounds 11 and 12 showed selective antibacterial against Pseudomonas aeruginosa with a minimum inhibitory concentration (MIC) of 17.4 and 13.9 µM, respectively. Compound 10 exhibited better α-glucosidase inhibitory activity than the assay control acarbose with IC50 values of 117.3 and 255.3 µM, respectively.