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.

2-(2-phenylethyl)chromone-sesquiterpene hybrids; Hainan agarwood; anti-inflammatory activity; cytotoxic activity; neuroprotective activity; structure elucidation.