Quinolinones Alkaloids with AChE Inhibitory Activity from Mangrove Endophytic Fungus Penicillium citrinum YX‐002

Abstract

AbstractAcetylcholinesterase (AChE) inhibitory activity‐guided studies on the mangrove‐derived endophytic fungus Penicillium citrinum YX‐002 led to the isolation of nine secondary metabolites, including one new quinolinone derivative, quinolactone A (1), a pair of epimers quinolactacin C1 (2) and 3‐epi‐quinolactacin C1 (3), together with six known analogs (4–9). Their structures were elucidated based on extensive mass spectrometry (MS) and 1D/2D nuclear magnetic resonance (NMR) spectroscopic analyses, and compared with data in the literature. The absolute configurations of compounds 1–3 was determined by combination of electronic circular dichroism (ECD) calculations and X‐Ray single crystal diffraction technique using CuKα radiation. In bioassays, compounds 1, 4 and 7 showed moderate AChE inhibitory activities with IC50 values of 27.6, 19.4 and 11.2 μmol/L, respectively. The structure‐activity relationships (SARs) analysis suggested that the existence of carbonyl group on C‐3 and the oxygen atom on the five‐membered ring were beneficial to the activity. Molecular docking results showed that compound 7 had a lower affinity interaction energy (−9.3 kcal/mol) with stronger interactions with different sites in AChE activities, which explained its higher activities.