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