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Indolizine Derivatives as HIV-1 VIF–ElonginC Interaction Inhibitors

Authors

  • Wenlin Huang,

    1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China
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  • Tao Zuo,

    1. National Engineering Laboratory for AIDS Vaccine, College of Life Science, Jilin University, Changchun, China
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  • Xiao Luo,

    1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China
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  • Hongwei Jin,

    1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China
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  • Zhenming Liu,

    1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China
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  • Zhenjun Yang,

    1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China
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  • Xianghui Yu,

    1. National Engineering Laboratory for AIDS Vaccine, College of Life Science, Jilin University, Changchun, China
    2. Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, College of Life Science, Jilin University, Changchun, China
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  • Liangren Zhang,

    Corresponding author
    • State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China
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  • Lihe Zhang

    1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China
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Corresponding author: Liangren Zhang, liangren@bjmu.edu.cn

Abstract

Compound 1 (VEC-5) was identified as a potent small-molecular HIV-1 viron infectivity factor inhibitor that targets the viron infectivity factor–ElonginC interaction. A structure–activity relationship study was carried out to develop compounds with improved efficacy against HIV-1 and 49 indolizine derivatives of three categories were designed and synthesized. We found that five compounds exhibited promising anti-HIV-1 activity, and the most active compound 2g had an IC50 value of 11.0 μm. These results provide new information to develop highly potent small-molecule HIV-1 viron infectivity factor inhibitors.

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