Design and Synthesis of a Series of Novel Bisquinazoline Glycosides as Epidermal Growth Factor Receptor Inhibitors

Authors

  • Shaopeng Chen,

    1. Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
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    • These authors contributed equally to this work.

  • Xiaowei Zhang,

    1. Division of Anti-tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China
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    • These authors contributed equally to this work.

  • Junlei Wang,

    1. Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
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  • Shengbiao Wan,

    1. Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
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  • Meiyu Geng,

    Corresponding author
    1. Division of Anti-tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China
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  • Tao Jiang

    Corresponding author
    1. Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
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Corresponding authors: Tao Jiang, jiangtao@ouc.edu.cn; Meiyu Geng, mygeng@mail.shcnc.ac.cn

Abstract

A new series of potential epidermal growth factor receptor inhibitors possessing bisquinazoline and saccharide moieties were designed and synthesized. The biological results demonstrated that the synthetic derivatives significantly inhibited epidermal growth factor receptor enzymatic activity in vitro. Of them, compound 14b showed the highest inhibitory rate toward epidermal growth factor receptor protein tyrosine kinase (81.36%) at a concentration of 1 μm. Further molecular simulation predicted that 14b offered its saccharide moieties hydrogen bonding to ATP-binding pocket.

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