title: Discovery of flavonoid derivatives as anti-HCV agents via pharmacophore search combining molecular docking strategy.
abstract: Common feature based pharmacophore and structure-based docking approaches have been employed in the identification of novel anti-HCV candidates from our in-house database. A total of 31 hits identified in silico were screened in vitro assay. 20 Compounds demonstrated anti-HCV activities (EC(50)<50 μM), including two naturally occurring flavones apigenin (21) and luteolin (22) with low micromole EC(50) values and three compounds (23, 24 and 25) of novel scaffolds with moderate potencies. In addition, pharmacophore refinement was also conducted based on the current knowledge of flavone-derived anti-HCV candidates and the results of combined in silico and in vitro assays.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Rd, Shanghai 201203, China.
authors.forename: Ming-Ming
authors.initials: MM
authors.lastname: Liu
authors.forename: Lu
authors.initials: L
authors.lastname: Zhou
authors.forename: Pei-Lan
authors.initials: PL
authors.lastname: He
authors.forename: Yi-Nan
authors.initials: YN
authors.lastname: Zhang
authors.forename: Jia-Yi
authors.initials: JY
authors.lastname: Zhou
authors.forename: Qing
authors.initials: Q
authors.lastname: Shen
authors.forename: Xin-Wen
authors.initials: XW
authors.lastname: Chen
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Zuo
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: De-Yong
authors.initials: DY
authors.lastname: Ye
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical; D005419:Flavonoids / Q000737:chemistry* / Q000494:pharmacology*; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D015203:Reproducibility of Results; D013329:Structure-Activity Relationship; D014584:User-Computer Interface; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D005419:Flavonoids; D008024:Ligands