Neuraminidase inhibitory activities of flavonols isolated from Rhodiola rosea roots and their in vitro anti-influenza viral activities

Five flavonols (3, 5, and 9–11) were isolated from Rhodiola rosea, and compared with commercially available flavonoids (1, 2, 4, 6–8, and 12–14) to facilitate analysis of their structure–activity relationship (SAR). All compounds (1–14) showed neuraminidase inhibitory activities with IC50 values ranging from 0.8 to 56.9 lM. The in vitro anti-influenza virus activities of flavonoids 1–6, 8–12, and 14 were evaluated using two influenza viral strains, H1N1 (A/PR/8/34) and H9N2 (A/Chicken/Korea/MS96/96), testing their ability to reduce virus-induced cytopathic effect (CPE) in MDCK cells. We found that the activity of these compounds ranged from 30.2 to 99.1 lM against H1N1- and 18.5 to 133.6 lM against H9N2-induced CPE. Of compounds 1–14, gossypetin (6) exhibited the most potent inhibitory activity, with IC50 values of 0.8 and 2.6 lM on neuraminidases from Clostridium perfringens and recombinant influenza virus A (rvH1N1),respectively. In contrast, kaempferol (3) exhibited the highest activity against two influenza viruses,H1N1 and H9N2 with EC50 values of 30.2 and 18.5 lM, respectively. Activity depended on the position and number of hydroxy groups on the flavonoids backbone. In kinetic studies, all isolated compounds behaved as noncompetitive inhibitors.