Furanocoumarins from the Roots of Cachrys cristata DC.: Isolation, Anticholinesterase Activity, and Molecular Docking Studies

Objectives: The present study aimed to investigate the phytochemical constituents of Cachrys cristata roots, to evaluate the cholinesteraseinhibitory activity of the isolated compounds, and to assess their possible binding interactions with acetylcholinesterase and butyrylcholinesterase through molecular docking studies. Materials and Methods:The roots were extracted with dichloromethane by Soxhlet extraction, and a coumarin-rich fraction was obtained by precipitation from the crude extract.Chromatographic purification of this fraction using Sephadex LH-20, reversed-phase C 18 column chromatography, and preparative thin-layer chromatography afforded ten known furanocoumarins: oxypeucedanin hydrate, oxypeucedanin, bergapten, xanthotoxin, 3'-hydroxyprantschimgin, oxypeucedanin ethanolate (oxypeucedanin hydrate-3"-ethyl ether), pabularinone, marmesin, pabulenol and saxalin.The structures of the isolated compounds were identified by (1)H NMR spectroscopy and comparison with literature data.Selected isolated compounds were evaluated for inhibitory activity against acetylcholinesterase and butyrylcholinesterase, and the results were further assessed by molecular docking.Results: The tested furanocoumarins showed weak cholinesterase inhibitory activity.Bergapten was the most active compound against acetylcholinesterase, with an IC 50 value of 92.15 µM.For butyrylcholinesterase, bergapten, and pabulenol exhibited measurable inhibition, with IC 50 values of 150.25 µM and 157.28 µM, respectively.Conclusion: This study contributes to the phytochemical characterization of Cachrys cristata roots and provides the first phytochemical evidence for the occurrence of furanocoumarin-type constituents in the roots of this species.The isolated compounds exhibited weak cholinesterase inhibitory activity, suggesting that the furanocoumarin scaffold may serve as a preliminary framework for further structural optimization rather than as a source of potent cholinesterase inhibitors.