Three unusual norlignans with anti-inflammatory from the resin of Styrax tonkinensis (Pierre) Craib ex Hart

Three unusual phenylisopentane norlignans, designated styraxolanes A-C (1–3), alongside three known analogues (4–6), were obtained from the Styrax tonkinensis resin. Structural assignment was achieved through comprehensive spectroscopic analysis (IR, HRESIMS, 1D- and 2D-NMR). With IC50 values of 7.51 and 8.99 µM, compounds 3 and 4 correspondingly exhibited significant suppression of nitric oxide (NO) production in LPS-stimulated macrophages. In contrast, compounds 1 and 2 displayed considerably weak activity (IC50 = 23.47 and 24.78 μM, respectively). These results suggest a clear structure-dependent bioactivity. This study expands the chemical diversity of bioactive constituents in Styrax species and provides potential candidates for anti-inflammatory agent development. This study reports the first isolation and identification of three novel phenylisopentane norlignans, styraxolanes A–C, from the resin of Styrax tonkinensis, with the benzoylsubstituted compound exhibiting notable anti-inflammatory activity. This work not only expands the chemical diversity of the genus Styrax but also provides new structural templates and bioactive lead compounds for the development of natural product-based anti-inflammatory agents. This study identifies the benzoyl moiety as a key pharmacophore for enhancing the anti-inflammatory activity of norlignans, providing clear structure-activity relationship guidance for developing new anti-inflammatory drugs. Compounds 3 and 4, which significantly inhibit the production of the inflammatory mediator NO at low micromolar concentrations, show promising drug development potential. They serve as a starting point for subsequent structural optimization and mechanistic studies, facilitating the development of natural anti-inflammatory agents.