Bioactive prenylated phenolic compounds from the aerial parts of Glycyrrhiza uralensis

In this work, a bioassay-guided fractionation strategy was used to isolate 26 phenolic compounds from the ethyl acetate partition of an ethanol extract of the aerial parts of Glycyrrhiza uralensis Fisch. ex DC. Among them, 8 prenylated phenolic compounds (glycyuralins Q-X) were described for the first time. The two enantiomers of glycyuralin Q were purified and their absolute configurations were established by ECD spectral calculations. (1″R, 2″S)-glycyuralin Q and (1″S, 2″R)-glycyuralin Q showed significant inhibitory activities against SARS-CoV-2 virus proteases 3CL^pro with IC₅₀ values of 1.5 ± 1.0 and 4.0 ± 0.3 μM, and PL^pro with IC₅₀ values of 2.4 ± 0.2 and 1.9 ± 0.1 μM, respectively. Four compounds showed potent cytotoxic activities against A549, Huh-7, and HepG2 human cancer cells with IC₅₀ values ranging from 0.5 to 2.5 μM.