title: The discovery of indole derivatives as novel hepatitis C virus inhibitors.
abstract: In this study, a library of in-house small molecule was screened using a HCV cell-based assay and a compound (1) containing an N-protected indole scaffold (NINS) was identified as a novel anti-HCV inhibitor. Through structure activity relationship (SAR) study, it was observed that the racemic inhibitor (10m) displayed good anti-HCV activity (EC50 = 1.02 ± 0.10 μM) with the excellent selectivity index (SI = 45.56). Interestingly, R-enantiomer ((R)-10m) showed better anti-HCV activity and lower cytotoxicity than S-enantiomer ((S)-10m). (R)-10m gave the best anti-HCV potency (EC50 = 0.72 ± 0.09 μM) with the highest selectivity index (SI > 69.44). In addition, the mechanism of action study of NINS derivatives demonstrated that NINS derivatives interfere with the early step (viral entry) of the HCV life cycle.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin 300353, People's Republic of China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Han
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin 300353, People's Republic of China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Liang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin 300353, People's Republic of China.
authors.forename: Yaxin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Structural Biology Laboratory, Tsinghua University, Beijing 100084, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Qing
authors.affiliation: Structural Biology Laboratory, Tsinghua University, Beijing 100084, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin 300353, People's Republic of China. Electronic address: shanglq@nankai.edu.cn.
authors.forename: Luqing
authors.initials: L
authors.lastname: Shang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin 300353, People's Republic of China. Electronic address: zheng_yin@nankai.edu.cn.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Yin
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D016174:Hepacivirus / Q000187:drug effects*; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D007211:Indoles
keywords: Chiral effect; Hepatitis C virus (HCV); Indole derivatives; Structure–activity relationship (SAR) study