Novel Naphthalimide–Benzoic Acid Conjugates as Potential Apoptosis-Inducing Agents: Design, Synthesis, and Biological Activity

Authors

  • Aibin Wu,

    Corresponding author
    1. School of Chemistry and Environmental Engineering, Yangtze University, Jingzhou 434023, China
    2. Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
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  • Ping Mei,

    1. School of Chemistry and Environmental Engineering, Yangtze University, Jingzhou 434023, China
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  • Yufang Xu,

    1. Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
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  • Xuhong Qian

    1. Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
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Corresponding author: Aibin Wu, abwu@yangtzeu.edu.cn

Abstract

A series of novel naphthalimide derivatives with 4-[4-(3,3-diphenylallyl)piperazin-1-yl]benzoic acid as side chain were designed and synthesized. Their antitumor activities were evaluated against a variety of cancer cell lines in vitro. Preliminary results showed that most of the derivatives had cytotoxic activity comparable with that of amonafide, with IC50 values of 10−6–10−5 m. Interestingly, compound 12e had the unique antitumor activity against MCF-7 among the cancer cell lines tested. More importantly, flow cytometric analysis indicated that compared with amonafide, the target compounds could effectively induce G2/M arrest and progress to apoptosis in HL-60 cells after double staining with annexin V–FITC and propidium iodide. The present work provided a novel class of naphthalimide-based derivatives with potential apoptosis-inducing and improved antitumor activity for further optimization.

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