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). Five undescribed chromene dimers, including four pair of racemates, were isolated from the leaves of Melicope pteleifolia using the molecular networking strategy. Melptelchromene E significantly inhibited the nitric oxide production. [Display omitted] •Molecular networking was used to search the chemical space of Melicope pteleifolia.•MS-guided isolation afforded five undescribed 2H-chromene dimers.•Four pairs of enantiomeric compounds were optically resolved.•Their absolute configurations were established by quantum mechanical calculations.•The 6,6-linked 2H-chromene dimers exhibited anti-inflammatory activity.