2-(2-Phenylethyl)chromone-Sesquiterpene Hybrids from Agarwood of Aquilaria sinensis: Characterization and Biological Activity Evaluation

Aquisinenins G-I (<b>1</b>-<b>3</b>), three new 2-(2-phenylethyl)chromone-sesquiterpene hybrids, were isolated from the ethanol extract of Hainan agarwood derived from <i>Aquilaria sinensis</i>. Spectroscopic techniques, such as ¹D and ²D NMR and HRESIMS, were used to determine their structures. Experimental and computed ECD data were compared to confirm their absolute configurations. Compounds <b>1</b>-<b>3</b> are uncommon dimeric derivatives of 2-(2-phenylethyl)chromone-sesquiterpene, characterized by the fusion of 5,6,7,8-tetrahydro-2-(2-phenylethyl)chromone with agarofuran or agarospirane-type sesquiterpene units by an ester linkage. Compound <b>1</b> inhibited nitric oxide production in lipopolysaccharide-stimulated RAW264.7 cells, showing an IC₅₀ value of 22.31 ± 0.42 μM. The neuroprotective effects of compounds <b>1</b> and <b>3</b> against H₂O₂-induced apoptosis were assessed in human neuroblastoma SH-SY5Y cells. Compound <b>1</b> demonstrated cytotoxicity with IC₅₀ values of 72.37 ± 0.20 μM against K562 and 61.47 ± 0.22 μM against BEL-7402, while compounds <b>2</b> and <b>3</b> showed cytotoxicity across all five tested human cancer cell lines.