Eremophilane Sesquiterpenes from a Deep Marine-Derived Fungus, Aspergillus sp. SCSIOW2, Cultivated in the Presence of Epigenetic Modifying Agents

• Published in: Molecules (Basel, Switzerland) Vol. 21; no. 4; p. 473
• Main Authors: Wang, Liyan, Li, Mengjie, Tang, Jianqiang, Li, Xiaofan
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 18.04.2016; MDPI AG
• Subjects: Animals; Aspergillus - chemistry; Aspergillus - drug effects; Azacitidine - pharmacology; ECD; Epigenesis, Genetic - drug effects; epigenetic modification; eremophilane; Fermentation; Histone Deacetylase Inhibitors - pharmacology; Hydroxamic Acids - pharmacology; marine fungus; Mice; Nitric Oxide - metabolism; nitric oxide inhibitory activity; Polycyclic Sesquiterpenes; RAW 264.7 Cells; Secondary Metabolism; Sesquiterpenes - chemistry; Sesquiterpenes - isolation & purification; Sesquiterpenes - pharmacology; epigenetic modification; eremophilane; nitric oxide inhibitory activity; marine fungus; ECD
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules21040473

Chemical epigenetic manipulation was applied to a deep marine-derived fungus, Aspergillus sp. SCSIOW2, resulting in significant changes of the secondary metabolites. Three new eremophilane-type sesquiterpenes, dihydrobipolaroxin B (2), dihydrobipolaroxin C (3), and dihydrobipolaroxin D (4), along with one known analogue, dihydrobipolaroxin (1), were isolated from the culture treated with a combination of histone deacetylase inhibitor (suberohydroxamic acid) and DNA methyltransferase inhibitor (5-azacytidine). 1-4 were not produced in the untreated cultures. 2 and 3 might be artificial because 1 could form 2 and 3 spontaneously in water by intracellular acetalization reaction. The absolute configurations of 1 and 2 were assigned based on ECD spectroscopy combined with time-dependent density functional theory calculations. All four compounds exhibited moderate nitric oxide inhibitory activities without cytotoxic effects.