Bioactive compounds from Beilschmiedia percoriacea leaves: isolation, structural characterization, and biological...

In this work, two previously undescribed sesquiterpenes, beilschmiedins A-B (1-2), as well as twelve known compounds (3-14), were obtained from the methanol extract of the Beilschmiedia percoriacea (B. percoriacea) leaves. Their structures were fully elucidated using a combination of spectroscopic techniques, including HR-ESI-MS, UV, and 1D/2D NMR, and compared with literature data. Furthermore, the absolute configurations of the new compounds 1 and 2 were determined by quantum chemical ECD calculations. Biologically, the fourteen isolates were evaluated for their anti-inflammatory, enzyme inhibitory, and antioxidant activities. Eleven compounds inhibited NO production more strongly than the positive control l-NAME. Among them, phillygenin (4), epi-pinoresinol (5), fargesin (6), and schisandlignan A (11) showed the most potent inhibitory effects (IC₅₀ = 9.8-17.2 µM). In enzyme inhibition assays, schisandlignan A (11) and 3',4'-dimethoxybenzoic acid (3″,4″-dimethoxyphenyl)-2-methyl-3-oxobutyl ester (14) exhibited exceptional α-glucosidase inhibitory potential (IC₅₀ = 6.2 ± 0.38 and 5.0 ± 0.46 µM, respectively), significantly outperforming acarbose, while kobusin (7), forsythialan B (8), and nectandrin E (13) showed moderate xanthine oxidase inhibition (IC₅₀ = 74.7-127.6 µM). For antioxidant activity, compound 5 possessed the strongest radical scavenging capacity, revealing that free phenolic hydroxyl groups enhanced potency. Furthermore, this study provides the first report of the anti-inflammatory activity of 11 and the α-glucosidase inhibition of 11 and 14, whereas the two new sesquiterpenes, 1 and 2, displayed only moderate anti-inflammatory effects and were inactive in the other assays. Molecular docking studies demonstrated that these bioactive compounds exhibit favorable binding affinities toward COX-2, XO, α-glucosidase, and Keap1, supporting their potential anti-inflammatory, antioxidant, antidiabetic, and anti-gout activities. The 200 ns molecular dynamics simulations further revealed stable complex behavior and limited structural deviation of the selected ligands within their respective binding sites.