Flavonoids From Fumana juniperina (Lag. ex Dunal) Aerial Parts: Chemical Characterization, Antioxidant, and Anticholinesterase Activities Supported by In Silico Analysis

The present study provides the first comprehensive phytochemical and biological investigation of Fumana juniperina, highlighting its potential as a previously unexplored source of bioactive flavonoids. Ten flavonoids were isolated and identified from the n-butanol fraction, including the rare (2S)-naringenin-8-sulfonic acid, previously reported only in Fumana montana, thereby expanding the chemotaxonomic knowledge of the genus Fumana. The fraction exhibited remarkable antioxidant activity in 2,2-diphenyl-1-picrylhydrazyl (DPPH^·) (IC₅₀: 9.35 ± 0.56 µg/mL), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS^·+) (IC₅₀: 4.32 ± 0.36 µg/mL), and cupric reducing antioxidant capacity (CUPRAC) (A₀.₅₀: 10.60 ± 0.15 µg/mL) assays, together with moderate acetylcholinesterase (AChE) inhibition (IC₅₀:79.46 µg/mL). Notably, molecular docking and PASS prediction identified quercetin-3-O-β-D-glucoside and myricetin-3-O-β-D-glucoside as promising AChE inhibitors, displaying predicted binding affinities comparable to galantamine (-9.8 kcal/mol). These findings support the growing interest in polyhydroxylated flavonoids as multifunctional natural scaffolds with potential relevance to oxidative stress and cholinergic dysfunction associated with neurodegenerative disorders. ADMET predictions further supported these findings, indicating favorable binding profiles and acceptable safety for selected flavonoids, while also identifying pharmacokinetic limitations of glycosylated derivatives. Together, these results establish F. juniperina as a valuable source of multifunctional flavonoids and provide a solid foundation for future structural optimization strategies targeting oxidative stress and cholinesterase-mediated neurodegenerative disorders.