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Design, synthesis, and anticancer activities of 8,9-substituted Luotonin A analogs as novel topoisomerase I inhibitors

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Abstract

A series of 8,9-substituted Luotonin A analogs were designed, synthesized, and evaluated for antiproliferative activity against four cancer cell lines. The structure–activity relationship study revealed that the in vitro anticancer activity of Luotonin A was significantly improved by the introduction of 8-piperazine group and the 5-deaza modification. Two promising compounds 6a and 7a displayed potent topoisomerase I inhibitory activity. And a rational binding mode of 7a with topoisomerase I–DNA complex was proposed based on the molecular docking study.

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Acknowledgements

This work was supported by the Scientific Research Project of Education Department of Hubei Province (D20192003).

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  1. These authors contributed equally: Yuanhang Xiang, Haiping Li

Authors and Affiliations

  1. Key Laboratory of Chinese Medicine Chemistry and Chinese Herbal Compound of Hubei Province, Hubei University of Chinese Medicine, 430065, Wuhan, China

    Yuanhang Xiang, Haiping Li, Jun Wang, Xiaozhi Peng, Chunling Hu & Laichun Luo

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  1. Yuanhang Xiang
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Xiang, Y., Li, H., Wang, J. et al. Design, synthesis, and anticancer activities of 8,9-substituted Luotonin A analogs as novel topoisomerase I inhibitors. Med Chem Res 30, 1512–1522 (2021). https://doi.org/10.1007/s00044-021-02749-y

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