title: Inhibitory effects of polyphenols toward HCV from the mangrove plant Excoecaria agallocha L.
abstract: Four new polyphenols namely excoecariphenols A-D (1-4) were isolated from the Chinese mangrove plant Excoecaria agallocha L. together with 23 known phenolic compounds. The structures of new compounds were elucidated on the basis of extensive spectroscopic analyses including IR, MS, NMR, and CD data. Excoecariphenols A and B presented as the unusual flavane-based 1-thioglycosides. Part of the isolated polyphenols were tested against hepatitis C NS3-4A protease and HCV RNA in huh 7.5 cells. Excoecariphenol D, corilagin, geraniin, and chebulagic acid showed potential inhibition toward HCV NS3-4A protease with IC(50) values in a range of 3.45-9.03μM, while excoecariphenol D and corilagin inhibited HCV RNA in huh 7.5 cells significantly. A primary structure-activity relationship (SAR) is discussed.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, PR China.
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Li
authors.forename: Shanjiang
authors.initials: S
authors.lastname: Yu
authors.forename: Dong
authors.initials: D
authors.lastname: Liu
authors.forename: Peter
authors.initials: P
authors.lastname: Proksch
authors.forename: Wenhan
authors.initials: W
authors.lastname: Lin
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D019665:Euphorbiaceae / Q000737:chemistry*; D006526:Hepatitis C / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D008968:Molecular Conformation; D059808:Polyphenols / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D012367:RNA, Viral / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D059808:Polyphenols; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases