Natural products with dual anti-SARS-CoV-2 activity and selective cytotoxicity against leukemia cells from Rhaponticum carthamoides

Abstract Rhaponticum carthamoides ( Leuzea carthamoides ) is a Siberian medicinal plant known for a variety of beneficial effects and traditionally used in Russia and Eastern Europe. However, its potential as a source of antiviral agents and compounds with selective cytotoxicity against cancer cells remains underexplored. In this study, nine flavonoids, including ( 2R )-eriodictyol 5-O-β-glucopyranoside, ( 2S )-eriodictyol 5-O-β-glucopyranoside, eriodictyol 7-O-β-glucopyranoside, eriodictyol, quercetagetin 7-O-β-glucopyranoside, 6-hydroxykaempferol 7-O-β-glucopyranoside, 6-methoxyquercetin 7-O-β-glucopyranoside, spinacetin 7-O-β-glucopyranoside and 6-methoxykaempferol 3-O-β-glucopyranoside were isolated and characterized from the plant’s leaves. Their individual structures were determined by 2D NMR spectroscopy techniques and mass spectrometry. The compounds were tested for cytotoxic activity against an acute myeloid leukemia (AML) cell line (MOLM-13), and two non-malignant cell lines representing kidney epithelium (NRK) and cardiomyocyte (H9c2). Three compounds, quercetagetin 7-O-β-glucopyranoside, 6-methoxyquercetin 7-O-β-glucopyranoside, and spinacetin 7-O-β-glucopyranoside showed selective cytotoxicity towards MOLM-13 cells at 28–50 µM concentrations with little or no effect on the non-malignant cells. Notably, spinacetin 7-O-β-glucopyranoside was effective against MOLM-13 cells without affecting the viability of the non-malignant NRK and H9c2 cells, and it showed synergistic activity with the bench-mark AML drug daunorubicin. In SARS-CoV-2 pseudovirus neutralization assays, spinacetin 7-O-β-glucopyranoside and 6-methoxykaempferol 3-O-β-glucopyranoside demonstrated significant antiviral activity against variant Omicron (XBB 1.5) and some antiviral activity against Delta (B.1.617.2.) in A549 ACE2/TMPRSS2 cells. These findings identify spinacetin 7-O-β-glucopyranoside as a promising dual-acting compound with both anti-leukemic and antiviral properties, emphasizing the relevance of natural products in modern drug discovery.