Discovery of flavonoid derivatives as anti-HCV agents via pharmacophore search combining molecular docking strategy

• DOI: 10.1016/j.ejmech.2012.03.002
• Publication Date: 2012-03-08T18:33:47Z
• Authors: Ming-Ming Liu; Lu Zhou; Pei-Lan He; Yi-Nan Zhang; Jia-Yi Zhou; Qing Shen; Xin-Wen Chen; Jian-Ping Zuo; Wei Li; De-Yong Ye
• Keywords: Flavonoids; Models, Molecular; 0301 basic medicine; Drug Evaluation, Preclinical; Molecular Conformation; Reproducibility of Results; Hepacivirus; Ligands; Virus Replication; Antiviral Agents; 3. Good health; Structure-Activity Relationship; User-Computer Interface; 03 medical and health sciences; Cell Line, Tumor; Drug Discovery; Humans

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.