title: Novel anilinocoumarin derivatives as agents against hepatitis C virus by the induction of IFN-mediated antiviral responses.
abstract: The hepatitis C virus (HCV) is the main cause of progressive liver disease, leading to the development of liver cirrhosis and hepatocellular carcinoma (HCC). Novel anilinocoumarins were synthesized, and their efficacy against HCV replication was evaluated. We demonstrated that 3-(3',4',5'-trimethoxyanilin-1'-yl)methylaminocoumarin (6) exhibited strong anti-HCV activity at protein and RNA levels at non-toxic concentrations, with an EC(50) value of 12 ± 0.3 μM and a selective index (SI) value of 10. Combined treatment of compound 6 and interferon-α (IFN) or telaprevir induced a significant decrease in HCV RNA levels, respectively. We also found that the anti-HCV replication effect of compound 6 was due to the induction of IFN-mediated antiviral responses. This is the first report demonstrating that coumarins inhibit viral replication through an IFN-mediated anti-viral response. Collectively, compound 6 possessed potent activities against HCV replication and could be a new lead compound with higher selectivity and less toxicity.
authors: School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
authors: Huang-Kai
authors: HK
authors: Peng
authors: Wei-Chun
authors: WC
authors: Chen
authors: Jin-Ching
authors: JC
authors: Lee
authors: Shiang-Yu
authors: SY
authors: Yang
authors: Cherng-Chyi
authors: CC
authors: Tzeng
authors: Ying-Ting
authors: YT
authors: Lin
authors: Shyh-Chyun
authors: SC
authors: Yang
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D016174:Hepacivirus / Q000187:drug effects* / Q000254:growth & development / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology*; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D003374:Coumarins; D016898:Interferon-alpha