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Design, synthesis, and biological evaluation of novel trimethoxyindole derivatives derived from natural products

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Abstract

Piperlongumine, a natural alkaloid, is reported to possess various biological activities. In this study, six analogs with indole moiety have been designed and synthesized using scaffold hopping strategy. They exhibited better antitumor activities than the parent piperlongumine without apparent toxicity in normal cells. Among them, 3-chloro-1-(5,6,7-trimethoxy-1-methyl-1H-indole-2-carbonyl)-5,6-dihydropyridin-2(1H)-one showed the best in vitro antitumor activity with the IC50 value improved in 4–8-fold against four cancer cell lines. In an A549 lung cancer xenograft model, it exhibited a tumor growth inhibition of 54.6%, which is much higher than that of parent piperlongumine (38.3%) and comparable to the positive drug doxorubicin (53.3%). The indole–piperlongumine provides a novel lead compound for anticancer drug discovery.

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Acknowledgements

This research was funded by the grants from Young Teacher Training Assistance Scheme of Shanghai Universities (ZZyy15096 to Y.W.), the National Natural Science Foundation of China (81673352 to Z.M. and 81872978 to C.Z.), and Introduction of Talent Research Start-up Fund of Shanghai Institute of Technology (YJ2015-12 to Y.W.).

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Authors and Affiliations

  1. School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai, China

    Fangliu Lu, Baobao Chen, Chuanhao Wang & Yuelin Wu

  2. School of Pharmacy, Second Military Medical University, Shanghai, China

    Chunlin Zhuang & Zhenyuan Miao

  3. Department of Medical Oncology, Nantong Tumor Hospital, Jiangsu, China

    Xiaodong Zhang

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  1. Fangliu Lu
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  2. Baobao Chen
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  3. Chuanhao Wang
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  4. Chunlin Zhuang
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  5. Zhenyuan Miao
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  6. Xiaodong Zhang
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  7. Yuelin Wu
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Correspondence to Zhenyuan Miao, Xiaodong Zhang or Yuelin Wu.

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Lu, F., Chen, B., Wang, C. et al. Design, synthesis, and biological evaluation of novel trimethoxyindole derivatives derived from natural products. Monatsh Chem 150, 1545–1552 (2019). https://doi.org/10.1007/s00706-019-02466-8

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  • DOI: https://doi.org/10.1007/s00706-019-02466-8

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