Alpha-glucosidase inhibitory compounds from Vietnamese lichen Usnea baileyi: in vitro and in silico aspects†

Abstract

Using a bio-guided isolation on the Vietnamese lichen Usnea baileyi based on alpha-glucosidase inhibition, eleven compounds were isolated and structurally elucidated, namely, protocetraric acid (1), 8′-methylstictic acid (2), stictic acid (3), 4,6-diformyl-8-hydroxy-3-methoxy-1,9-dimethyl-11-oxo-11H-dibenzo[b,e][1,4]dioxepine-7-carboxylic acid (4), vicanicin (5), norstictic acid (6), diffractaic acid (7), barbatic acid (8), atranol (9), 5-chlorohaematommic acid (10), and eumitrin A1 (11). Their chemical structures were identified by extensive 1D and 2D NMR analysis and high-resolution mass spectroscopy and compared with those reported in literature. Protocetraric acid (1) and norstictic acid (6) were selected for further modification to derive new compounds, namely, 1a–1e and 6a. Both isolated and synthesized compounds were assessed for their alpha-glucosidase inhibitory activity. Compounds 1–6, 1a–1e, 6a, and 11 showed significant alpha-glucosidase inhibition with IC₅₀ values ranging from 10.4 to 130 μM. Molecular docking was applied to the most active compounds 1–3, 6, 1a–1e, and 6a to clarify the inhibitory mechanism. Compound 1e was determined to be a mixed inhibitor through a kinetic study.