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Design, synthesis and biological evaluation of novel 1,5-disubstituted isatin derivatives as antitumor agents

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Abstract

Isatin (1H-indole-2,3-dione) was reported to possess anticancer activities through its effect on tumor proliferation, apoptosis, and metastasis in vitro and in vivo. Here, we described the synthesis of a novel series of 1,5-disubstituted isatin derivatives with 2-indolinone scaffold as antitumor agents. Most of the synthesized compounds revealed potent antiproliferative effects in mantle cell lymphoma (MCL) cell lines, among which 7l possessed promising activities with IC50 values ranging from 0.4 to 1.3 μM. Following flow cytometric analysis, compound 7l efficiently arrested the cell cycle at G2/M phase, and induced apoptosis. Thus, this study shows promise in therapeutics of 1,5-disubstituted isatin derivatives in MCL and provides novel potential and efficient antitumor agents.

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Acknowledgements

This work was supported by the Key Research and Development Project of Shandong Province, China (Nos. 2017CXGC1401 and 2019GSF108038).

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Authors and Affiliations

  1. Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, PR China

    Huijun Zhuo, Zhen Zhang, Jingya Zhang & Guisen Zhao

  2. Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

    Yang Liu

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  1. Huijun Zhuo
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  2. Zhen Zhang
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  3. Yang Liu
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  4. Jingya Zhang
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  5. Guisen Zhao
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Correspondence to Guisen Zhao.

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Zhuo, H., Zhang, Z., Liu, Y. et al. Design, synthesis and biological evaluation of novel 1,5-disubstituted isatin derivatives as antitumor agents. Med Chem Res 29, 2170–2180 (2020). https://doi.org/10.1007/s00044-020-02627-z

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  • DOI: https://doi.org/10.1007/s00044-020-02627-z

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