Biologically guided isolation and ADMET profile of new factor Xa inhibitors from Glycyrrhiza glabra roots using in vitro and in silico approaches

• Published in: RSC advances Vol. 11; no. 17; pp. 9995 - 10001
• Main Authors: Ibrahim, Reham S, Mahrous, Rahma S R, Abu El-Khair, Rasha M, Ross, Samir A, Omar, Abdallah A, Fathy, Hoda M
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 09.03.2021; The Royal Society of Chemistry
• Subjects: Anticoagulants; Chemistry; Coagulation; Coronaviruses; COVID-19; Flavonoids; Inhibitors; Isomers; NMR; Nuclear magnetic resonance; Viral diseases
• ISSN: 2046-2069; 2046-2069
• DOI: 10.1039/d1ra00359c

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 ( ) root extract furnished ten flavonoids. By detailed analysis of their H, C NMR and MS data, the structures of these flavonoids were established as 7,4'-dihydroxyflavone (1), formononetin (2), 3- -glabridin (3), isoliquiritigenin (4), liquiritin (5), naringenin 5- -glucoside (6), 3,3',4,4'-tetrahydroxy-2-methoxychalcone (7), liquiritinapioside (8) and the two isomers isoliquiritigenin-4'- -β-d-apiosylglucoside (9) and isoliquiritigenin-4- -β-d-apiosylglucoside (10). All the isolated compounds were assessed for their FXa inhibitory activity using chromogenic assay for the first time. Liquirtin (5) showed the most potent inhibitory effects with an IC of 5.15 μM. The QikProp module was implemented to perform ADMET predictions for the screened compounds.