title: C-Methylated Flavonoids from Cleistocalyx operculatus and Their Inhibitory Effects on Novel Influenza A (H1N1) Neuraminidase.
abstract: 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.
authors.affiliation: BK21 Project Team, College of Pharmacy, Chosun University, 375 Seosuk-dong, Dong-gu, Gwangju 501-759, Republic of Korea.
authors.forename: Trong-Tuan
authors.initials: TT
authors.lastname: Dao
authors.forename: Bui-Thanh
authors.initials: BT
authors.lastname: Tung
authors.forename: Phi-Hung
authors.initials: PH
authors.lastname: Nguyen
authors.forename: Phuong-Thien
authors.initials: PT
authors.lastname: Thuong
authors.forename: Sung-Sik
authors.initials: SS
authors.lastname: Yoo
authors.forename: Eun-Hee
authors.initials: EH
authors.lastname: Kim
authors.forename: Sang-Kyum
authors.initials: SK
authors.lastname: Kim
authors.forename: Won-Keun
authors.initials: WK
authors.lastname: Oh
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects*; D053127:Influenza A Virus, H9N2 Subtype; D007251:Influenza, Human / Q000188:drug therapy; D020128:Inhibitory Concentration 50; D007700:Kinetics; D015394:Molecular Structure; D027822:Myrtaceae / Q000737:chemistry*; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D053139:Oseltamivir / Q000494:pharmacology
chemical_list: D000998:Antiviral Agents; D005419:Flavonoids; D053139:Oseltamivir; D009439:Neuraminidase