Xanthine oxidase inhibitory evaluation of prenylated flavonoids from peanut (Arachis hypogaea L.) shells: in vitro and in silico molecular docking studies.

Sustainable agriculture has become a crucial priority because the improper management of agricultural waste currently contributes to greenhouse gas emissions, as well as soil and air pollution. The shells of Arachis hypogaea L., which is commonly discarded as an agricultural by-product, have been reported to contain various secondary metabolites, including flavonoids, stilbenes, triterpenoids, etc. This work led to the isolation of two new prenylated flavonoids, arachisflavones A (1) and B (2), together with five prenylated flavones (3-7), two prenylated chalcones (8-9), and three prenylated flavanones (10-12) from the EtOAc extract of peanut shells. Notably, this is the first report isolating prenylated flavonoids from the Arachis genus and evaluating their xanthine oxidase (XO) inhibitory activity. The XO inhibitory assays revealed that 6/12 isolated compounds showed inhibitory activity, with IC50 values ranging from 0.256 to 59.1 µM. Among them, yinyanghuo E (6) showed the strongest XO inhibitory effect with an IC50 value of 0.256 ± 0.008 µM (95% CI: 0.238 to 0.275), comparable with the positive controls, allopurinol (IC50 = 2.34 ± 0.08 µM) (95% CI: 2.17 to 2.52) and febuxostat (IC50 = 0.018 ± 0.002 µM) (95% CI: 0.014 to 0.022). Molecular docking suggested that the active compounds exhibited favorable docking scores through interactions with key catalytic residues, including Arg880, Thr1010, Phe914, and Phe1009. Furthermore, ADMET prediction analysis revealed that arachis flavones A (1) possessed the most favorable predicted drug-likeness properties among the isolated compounds.