2--4--dihydroxy-6--methoxy-3--5--dimethylchalcone and Influenza--Human

As part of an ongoing study focused on the discovery of anti-influenza agents from plants, four new (1-4) and 10 known (5-14) C-methylated flavonoids were isolated from a methanol extract of Cleistocalyx operculatus buds using an influenza H1N1 neuraminidase inhibition assay. Compounds 4, 7, 8, and 14, with a chalcone skeleton, showed significant inhibitory effects on the viral neuraminidases from two influenza viral strains, H1N1 and H9N2. Compound 4 showed the strongest inhibitory activity against the neuraminidases from novel influenza H1N1 (WT) and oseltamivir-resistant novel H1N1 (H274Y mutant) expressed in 293T cells with IC50 values of 8.15 ± 1.05 and 3.31 ± 1.34 μM, respectively. Compounds 4, 7, 8, and 14 behaved as noncompetitive inhibitors in the kinetic studies. These results indicate that C-methylated flavonoids from C. operculatus have the potential to be developed as neuraminidase inhibitors for novel influenza H1N1.

Topics: Antiviral Agents; Flavonoids; HEK293 Cells; Humans; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H9N2 Subtype; Influenza, Human; Inhibitory Concentration 50; Kinetics; Molecular Structure; Myrtaceae; Neuraminidase; Oseltamivir