Discovering novel 3-nitroquinolines as a new class of anticancer agents1

Authors

  • Hai-hong LI,

    1. Drug Discovery and Design Centre, State Key Laboratory of Drug Research, Chinese Academy of Sciences, Shanghai 201203, China
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    • 2

      These two authors contributed equally to this work.

  • He HUANG,

    1. Drug Discovery and Design Centre, State Key Laboratory of Drug Research, Chinese Academy of Sciences, Shanghai 201203, China
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    • 2

      These two authors contributed equally to this work.

  • Xiu-hua ZHANG,

    1. Division of Anti-Tumor Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
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  • Xiao-min LUO,

    1. Drug Discovery and Design Centre, State Key Laboratory of Drug Research, Chinese Academy of Sciences, Shanghai 201203, China
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  • Li-ping LIN,

    Corresponding author
    1. Division of Anti-Tumor Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
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  • Hua-liang JIANG,

    1. Drug Discovery and Design Centre, State Key Laboratory of Drug Research, Chinese Academy of Sciences, Shanghai 201203, China
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  • Jian DING,

    1. Division of Anti-Tumor Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
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  • Kaixian CHEN,

    1. Drug Discovery and Design Centre, State Key Laboratory of Drug Research, Chinese Academy of Sciences, Shanghai 201203, China
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  • Hong LIU

    Corresponding author
    1. Drug Discovery and Design Centre, State Key Laboratory of Drug Research, Chinese Academy of Sciences, Shanghai 201203, China
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  • 1

    Project supported by grants from the State Key Program of Basic Research of China (No 2006BAI01B02), the National Natural Science Foundation of China (No 20721003 and 20872153), and the 863 Hi-Tech Program of China (No 2006AA020602).

Correspondence to Prof Hong LIU. Phn 86-21-5080-7042. Fax 86-21-5080-7088. E-mail hliu@mail.shcnc.ac.cn

Abstract

Aim: To design and synthesize a novel class of antitumor agents, featuring the 3-nitroquinoline framework. Methods: Based on the enzyme-binding features of Ekb1, introducing a nitro group at the 3-position of the quinoline core, a series of novel 3-nitroquinolines was designed and synthesized. The inhibition of epidermal growth factor receptor (EGFR) activity by these compounds was evaluated and analyzed by the sulforhodamine B assay for their inhibitory activities toward human epidermoid carcinoma (A431) cells and breast cancer (MDA-MB-468) cells, which are known to overexpress the EGFR kinase. Results: A series of novel 3-nitroquinoline derivatives were synthesized and evaluated for their antiproliferative effect against the EGFR-overexpressing tumor cell lines. Several compounds for concentration-response studies showed prominent inhibitory activities with IC50 values in the micromolar or nanomolar range. The structure-activity relationship was discussed in terms of the inhibitory activity against the proliferation of 2 human carcinoma cell lines. Conclusion: This study was the first to identify new structural types of antiproliferative agents against the EGFR-overexpressing tumor cell lines by the incorporation of the nitro group at the 3-position of the quinoline core structure, providing promising new templates for the further development of anticancer agents.

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