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Synthesis and anticancer activities of thiosemicarbazones derivatives of thiochromanones and related scaffolds

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Abstract

A series of novel thiosemicarbazone analogs (4a–t, 6a–j) were synthesized and evaluated for their cytotoxic activities. The obtained results showed that thiochromanone-based thiosemicarbazones substituted primarily at the C-8 position exhibited higher cytotoxicity than the corresponding 1,1-dioxo-thiochromanone-, benzothiazepine-, and 1,1-dioxo-benzothiazepine-based analogs. Significantly, compound 4c (8-fluoro thiochromanone thiosemicarbazone) was found to be the most active and exhibited potent cytotoxicity against the MCF-7, SK-mel-2, and DU145 cancer cell lines, with IC50 values of 0.42, 0.58, and 0.43 µM, respectively. In addition, the mechanism of compound 4c induced MCF-7 cell apoptosis was preliminarily investigated through cell cycle, Annexin V-FITC/PI staining, and ROS assays, indicating that compound 4c may exert its anticancer property through ROS-mediated apoptosis.

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Acknowledgements

This work was financially supported by the National Natural Science Foundation of China (No. 21502085), Special Funds for Public Welfare Research and Capacity Building of Guangdong Province (Nos. 2016A010103042 and 2015A020211038), the Research Group of Rare Earth Resource Exploiting and Luminescent Materials (2017KCXTD022), and Lingnan Normal University Science Research Foundation (No. ZL1401).

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  1. School of Chemistry & Chemical Engineering, Lingnan Normal University, Cunjin Road 29, Chikan District, Zhanjiang, 524048, Guangdong, PR China

    Jiangli Song, Rongkai Pan, Guobi Li, Wenyi Su, Jincheng Li & Shenggui Liu

  2. Key Laboratory of Clean Energy Materials Chemistry of Guangdong Higher Education Institute, Cunjin Road 29, Chikan District, Zhanjiang, 524048, Guangdong, PR China

    Jiangli Song, Rongkai Pan, Guobi Li & Shenggui Liu

  3. Industrial Technology Research Institute, Lingnan Normal University, Cunjin Road 29, Chikan District, Zhanjiang, 524048, Guangdong, PR China

    Xiumei Song

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  1. Jiangli Song
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Song, J., Pan, R., Li, G. et al. Synthesis and anticancer activities of thiosemicarbazones derivatives of thiochromanones and related scaffolds. Med Chem Res 29, 630–642 (2020). https://doi.org/10.1007/s00044-020-02503-w

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