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European journal of medicinal chemistry v.143, 2018년, pp.1053 - 1065   SCI SCIE
본 등재정보는 저널의 등재정보를 참고하여 보여주는 베타서비스로 정확한 논문의 등재여부는 등재기관에 확인하시기 바랍니다.

Discovery and evolution of aloperine derivatives as a new family of HCV inhibitors with novel mechanism

Zhang, Xin (Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China ) ; Lv, Xiao–Qin (Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China ) ; Tang, Sheng (Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China ) ; Mei, Lin (Qingdao Municipal Hospital, Qingdao 266011, China ) ; Li, Ying–Hong (Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China ) ; Zhang, Jing–Pu (Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China ) ; Jiang, Jian–Dong (Beijing Key Laboratory of Antimicrobial Agents, Institute ) ; Peng, Zong–Gen ; Song, Dan–Qing ;
  • 초록  

    Abstract Aloperine ( 1 ), a Chinese natural product with a unique endocyclic scaffold, was first identified to be a potent hepatitis C virus (HCV) inhibitor in our laboratory. Thirty-four new aloperine derivatives were designed, synthesized and evaluated for their anti-HCV activities taking 1 as the lead. Among them, compound 7f exhibited the potential potency with EC 50 values in a micromolar range against both wild-type and direct-acting antiviral agents (DAAs)-resistant variants, and synergistically inhibited HCV replication with approved DAAs. Furthermore, it also owned a good oral pharmacokinetic and safety profile, suggesting a highly druglike nature. The primary mechanism showed that 7f might target host components, distinctly different from the DAAs currently used in clinic. Therefore, we consider aloperine derivatives to be a novel class of anti-HCV agents, and compound 7f has been selected as a promising antiviral candidate for further investigation. Highlights New aloperine derivatives were synthesized and evaluated for the anti-HCV activity. Compound 7f synergistically inhibited HCV replication with approved DAAs. Compound 7f owned a good oral pharmacokinetic and safety profile. 7f might target host components, distinctly different from the DAAs used in clinic. Graphical abstract [DISPLAY OMISSION]


  • 주제어

    Aloperine .   HCV .   Structure−activity relationship .   Host components .   Druglike.  

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