title: Discovery of Imidazo[1,2-α][1,8]naphthyridine Derivatives as Potential HCV Entry Inhibitor.
abstract: RO8191 represents a newly discovered small-molecule IFN-like agent that displays potent anti-HCV activity. With it as lead, a series of compounds bearing an imidazo[1,2-α][1,8]naphthyridine core and an amide bond-linked side chain were designed and synthesized. These compounds were evaluated on HCV cell culture system (HCVcc-hRluc-JFH1), and some of them exhibited remarkable anti-HCV activity (EC50 = 0.017-0.159 μM) and low toxicity (CC50 > 25 μM). Moreover, it was revealed that these newly identified anti-HCV agents exert their antiviral effect through a distinct mechanism of action from that of RO8191 by targeting the viral entry process. Thus, our study provides a starting point for the development of potential HCV entry inhibitor.
authors.affiliation: Comprehensive AIDS Research Center, and Department of Pharmacology and Pharmaceutical Sciences, School of Medicine, Tsinghua University , Beijing 100084, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Comprehensive AIDS Research Center, and Department of Pharmacology and Pharmaceutical Sciences, School of Medicine, Tsinghua University , Beijing 100084, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Wang
authors.affiliation: Comprehensive AIDS Research Center, and Department of Pharmacology and Pharmaceutical Sciences, School of Medicine, Tsinghua University , Beijing 100084, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Comprehensive AIDS Research Center, and Department of Pharmacology and Pharmaceutical Sciences, School of Medicine, Tsinghua University , Beijing 100084, China ; Collaborative Innovation Center for Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University , Chengdu 610041, China.
authors.forename: Ligong
authors.initials: L
authors.lastname: Chen
authors.affiliation: Comprehensive AIDS Research Center, and Department of Pharmacology and Pharmaceutical Sciences, School of Medicine, Tsinghua University , Beijing 100084, China.
authors.forename: Yongguang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University , Beijing 100084, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Qing
authors.affiliation: Comprehensive AIDS Research Center, and Department of Pharmacology and Pharmaceutical Sciences, School of Medicine, Tsinghua University , Beijing 100084, China.
authors.forename: Shengdian
authors.initials: S
authors.lastname: Huang
authors.affiliation: Comprehensive AIDS Research Center, and Department of Pharmacology and Pharmaceutical Sciences, School of Medicine, Tsinghua University , Beijing 100084, China.
authors.forename: Yuanhao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Comprehensive AIDS Research Center, and Department of Pharmacology and Pharmaceutical Sciences, School of Medicine, Tsinghua University , Beijing 100084, China.
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Lei
authors.affiliation: Comprehensive AIDS Research Center, and Department of Pharmacology and Pharmaceutical Sciences, School of Medicine, Tsinghua University , Beijing 100084, China ; Collaborative Innovation Center for Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University , Chengdu 610041, China.
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Comprehensive AIDS Research Center, and Department of Pharmacology and Pharmaceutical Sciences, School of Medicine, Tsinghua University , Beijing 100084, China.
authors.forename: Zhilong
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University , Beijing 100084, China.
authors.forename: Linqi
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Comprehensive AIDS Research Center, and Department of Pharmacology and Pharmaceutical Sciences, School of Medicine, Tsinghua University , Beijing 100084, China ; Collaborative Innovation Center for Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University , Chengdu 610041, China.
authors.forename: Yefeng
authors.initials: Y
authors.lastname: Tang
keywords: Hepatitis C virus; IFN-like compound; RO8191; anti-HCV agent; entry inhibitor