2026-10-10T13:42:12Z https://www.scidb.cn/oai

10.57760/sciencedb.nprd.00345 2026-08-12T09:34:39Z

2026-08-12 Benzofuran-type constituents from the roots of Eupatorium chinense and their MAO-B inhibitory activity doi:10.57760/sciencedb.nprd.00345 en This study investigated the roots of Eupatorium chinense L. to identify benzofuran-type chemical constituents with monoamine oxidase B (MAO-B) inhibitory activity, and to perform structural modification of the major component 12,13-dihydroxyeuparin for preliminary structure–activity relationship analysis. 12,13-Dihydroxyeuparin is a natural hydroxylated derivative of euparin, sharing the same benzofuran core scaffold. Euparin has been reported to exhibit antidepressant activity; however, its poor water solubility and low bioavailability limit further development. 12,13-Dihydroxyeuparin, bearing two additional hydroxyl groups at C-12 and C-13, shows improved water solubility and possesses acetylcholinesterase (AChE) inhibitory activity; however, its MAO-B inhibitory activity remains unreported. On this basis, it was selected as the lead compound for structural modification. Seven compounds were identified as:12,13-dihydroxyeuparin (1), euparin (2), euparone (3), 6-acetyl-7-hydroxy-2,3-dimethylchromone (4), 3β,6-hydroxytremetone (5), (2R,3S)-5-acetyl-6-hydroxy-2-isopropenyl-3-ethoxy-2,3-dihydrobenzofuran (6), and 1-[(2R,3S)-3-ethoxy-2,3-dihydro-6-hydroxy-2-(1-methylethenyl)-1-benzofuran-5-yl]ethanone (7). Using 12,13-dihydroxyeuparin (1), the major constituent from the roots, as the lead compound, 13 derivatives were synthesized via dihydroxyl acetylation, phenolic hydroxyl benzylation, and carbonyl Aldol condensation. All synthetic products were confirmed by ¹H NMR, ¹³C NMR, and LC-MS. The MAO-B inhibitory activities of the seven isolated compounds and 13 synthetic derivatives were evaluated using a fluorescence-based assay, with selegiline as the positive control (IC50 = 7 ± 0.86 μM). Among the natural compounds, compound 4 (chromone) exhibited the most potent activity (IC50 = 3 ± 0.65 μM), approximately 2.3-fold more potent than selegiline. The benzylated derivatives 2b–7b showed improved activity compared with the parent compound 1, with the p -bromobenzyl-substituted derivative 7b displaying the best activity (IC50 = 11 ± 0.27 μM). Structure–activity relationship analysis indicated that the chromone scaffold is a promising MAO-B inhibitory core, the free hydroxyl groups at C-12/C-13 are critical pharmacophores, and the introduction of a bromobenzyl group at the C-7 position significantly enhances MAO-B inhibitory activity. Eupatorium chinense; benzofuran; 12; 13-dihydroxyeuparin; structural modification; monoamine oxidase B Tian Chenchen EMBARGO https://creativecommons.org/licenses/by-nc/4.0/ dataset Science Data Bank