Molecular networking-based discovery of anti-inflammatory chromene dimers from Melicope pteleifolia

With the aid of a feature-based molecular networking strategy, five undescribed C₂ and C₁ symmetric chromene dimers, namely, melptelchromenes A-E, were isolated from the leaves of Melicope pteleifolia. Four asymmetric dimers were found to be racemates and were resolved by chiral phase HPLC analyses. Their structures, including absolute configurations, were elucidated by HRMS, NMR spectroscopy, and quantum mechanical calculations of ECD spectra and NMR chemical shifts. Melptelchromenes A-D possess a unique ethylidene linkage via two 2H-chromene cores, while melptelchromene E represents the first example of a dimeric chromene featuring a 1,3-diarylbutan-1-ol moiety. Of these compounds, 6,6'-linked dimeric chromenes showed nitric oxide inhibitory activities on lipopolysaccharide-induced RAW 264 cells, and (-)- and (+)-melptelchromene E were the two most potent compounds (IC₅₀, 3.0 and 5.1 μM, respectively).