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Synthesis and antitumor evaluation of novel fused heterocyclic 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole derivatives

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Abstract

In this study, twenty three 3,6-disubstituted 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole derivatives were synthesized and their antiproliferative activities in vitro were studied against SMMC-7721, HeLa, A549, and L929 by the CCK-8 assay. The bioassay results demonstrated that all tested compounds 8(a–w) exhibited antiproliferation with different degrees, and some compounds showed better effects than reference drug 5-fluorouracil. Among these screened compounds, compounds 8a, 8d, and 8l displayed significant antitumor activities in inhibiting SMMC-7721cell proliferation with IC50 values of 1.64, 1.74, and 1.61 µM, respectively. Compounds 8d and 8l were manifested highly effective biological activity versus HeLa cells with IC50 values of 2.23 and 2.84 µM, respectively. Compound 8l was found to have the highest antitumor potency against A549 cells with IC50 value of 2.67 µM. Furthermore, all compounds exhibited weaker cytotoxic effects than 5-fluorouracil on normal cell lines L929.

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Acknowledgements

We are grateful to the Tianjin Municipal Natural Science Foundation (18JCYBJC94900) and Training Project of Innovation Team of Colleges and Universities in Tianjin (TD13-5020) for financial support.

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Authors and Affiliations

  1. School of Chemistry and Chemical Engineering, Tianjin Key Laboratory of Organic Solar Cells And Photochemical Conversion, Tianjin University of Technology, Tianjin, 300384, China

    Xiao-Jia Liu, Hai-Ying Liu, Hai-Xin Wang, Yan-Ping Shi, Rui Tang, Shuai Zhang & Bao-Quan Chen

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  1. Xiao-Jia Liu
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  4. Yan-Ping Shi
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Liu, XJ., Liu, HY., Wang, HX. et al. Synthesis and antitumor evaluation of novel fused heterocyclic 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole derivatives. Med Chem Res 28, 1718–1725 (2019). https://doi.org/10.1007/s00044-019-02409-2

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