New prenylated indole-benzodiazepine-2,5-diones with α-glucosidase inhibitory activities from the mangrove-derived Aspergillus spinosus

Abstract

Mangrove-derived fungi have been demonstrated to be promising source of structurally diverse and widely active secondary metabolites. During our search for new bioactive compounds, eight new indole-benzodiazepine-2,5-dione derivatives asperdinones A–H (1–8) and two known congeners (9 and 10) were isolated from the culture extracts of the mangrove-derived fungus Aspergillus spinosus WHUF0344 guided by one strain many compounds (OSMAC) and the heteronuclear 1H, 13C single-quantum coherence (HSQC) based small molecule accurate recognition technology (SMART) strategies. The structures and absolute configurations of the new compounds were elucidated by detailed spectroscopic analyze and electronic circular dichroism (ECD) calculations. The putative biosynthetic pathway of these compounds was proposed. Compounds 1–10 were evaluated for their antibacterial and α-glucosidase inhibitory activities. None of compounds showed antibacterial activity. Compounds 2–6 and 8 exhibited moderate inhibitory effects against α-glucosidase with IC50 values in the range of 24.65–312.25 μM. Besides, both 3 and 4 inhibited α-glucosidase variedly. Furthermore, the molecular docking study showed that compounds 2–4 were perfectly docking into the active sites of α-glucosidase. This study not only enriched the chemical diversity of secondary metabolites from the mangrove-derived fungi, but also provided potential hit compounds for further development of α-glucosidase inhibitors.