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

Aquisinenins G-I (1-3), three new 2-(2-phenylethyl)chromone-sesquiterpene hybrids, were isolated from the ethanol extract of Hainan agarwood derived from Aquilaria sinensis. 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 1-3 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 1 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 1 and 3 against H2O2-induced apoptosis were assessed in human neuroblastoma SH-SY5Y cells. Compound 1 demonstrated cytotoxicity with IC50 values of 72.37 ± 0.20 μM against K562 and 61.47 ± 0.22 μM against BEL-7402, while compounds 2 and 3 showed cytotoxicity across all five tested human cancer cell lines.