Selective factor Xa inhibitors effectively block coagulation cascade with a broader therapeutic window than multitargeted anticoagulants. They have evolved as a crucial part of prevention and treatment of thromboembolic diseases and in therapeutic protocols involved in many clinical trials in coronavirus disease 2019 (COVID-19) patients. Biologically-guided isolation of specific FXa inhibitors from licorice (Glycyrrhiza glabra) root extract furnished ten flavonoids. By detailed analysis of their 1H, 13C NMR and MS data, the structures of these flavonoids were established as 7,4'-dihydroxyflavone (1), formononetin (2), 3-R-glabridin (3), isoliquiritigenin (4), liquiritin (5), naringenin 5-O-glucoside (6), 3,3',4,4'-tetrahydroxy-2-methoxychalcone (7), liquiritinapioside (8) and the two isomers isoliquiritigenin-4'-O-β-d-apiosylglucoside (9) and isoliquiritigenin-4-O-β-d-apiosylglucoside (10). All the isolated compounds were assessed for their FXa inhibitory activity using in vitro chromogenic assay for the first time. Liquirtin (5) showed the most potent inhibitory effects with an IC50 of 5.15 μM. The QikProp module was implemented to perform ADMET predictions for the screened compounds.
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