Phytochemical Constituents from Ardisia sylvestris Pitard Leaves: Enzyme Inhibition, Antioxidant, and Antimicrobial Activities with Molecular Simulation Insights

A phytochemical investigation of the ethanolic extract of Ardisia sylvestris Pitard leaves led to the isolation and identification of eight compounds, including 3S,5R,6R,9S-tetrahydroxymegastigman-7-ene (1), myricetin-3-O-rutinoside (2), phenyl ethyl-O-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranoside (3), 2-O-(trans-coumaroyl)malic acid 1-methyl ester (4), adenosine (5), gallic acid (6), 5-(8Z-heptadecenyl)resorcinol (7), and mandelic acid (8). Their structures were identified by NMR analysis, supported by MS data where available and comparison with published spectroscopic data. The isolated compounds were evaluated for α-glucosidase inhibitory, acetylcholinesterase (AChE) inhibitory, antioxidant, and antimicrobial activities. Among them, compound 7 showed the most promising biological profile, showing potent α-glucosidase inhibition (IC50 = 7.56 μg/mL), markedly stronger than acarbose (IC50 = 151.09 μg/mL), together with moderate AChE inhibitory activity (IC50 = 14.75 μg/mL). Compound 7 also displayed strong DPPH radical-scavenging activity (IC50 = 10.04 μg/mL), comparable to quercetin, and moderate antibacterial activity against Staphylococcus aureus (MIC = 64 μg/mL). Molecular docking and molecular dynamics simulations revealed favorable binding modes and stable interactions of compound 7 within the active sites of α-glucosidase and AChE. For the antibacterial activity, substrate-similarity-based target prioritization followed by comparative docking highlighted FabI as the highest-priority candidate target for compound 7. These findings identify 5-(8Z-heptadecenyl)resorcinol as a multifunctional bioactive constituent of A. sylvestris and provide complementary structural insights into its interactions with α-glucosidase and acetylcholinesterase.