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Design, synthesis and antiproliferative evaluation of novel sulfanilamide-1,2,3-triazole derivatives as tubulin polymerization inhibitors

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Summary

Microtubule as an important target in the cancer therapy was used to design novel tubulin polymerization inhibitors. Sulfanilamide-1,2,3-triazole hybrids were designed by a molecular hybridization strategy and their antiproliferative activity against three selected cancer cell lines (BGC-823, MGC-803 and SGC-7901) were evaluated. All sulfanilamide-1,2,3-triazole hybrids displayed potent inhibitory activity against all cell lines. In particular, compound 10b showed the most excellent inhibitory effect against MGC-803 cells, with an IC50 value of 0.4 μM. Cellular mechanism studies elucidated that 10b induced apoptosis by decreasing the expression level of Bcl-2 and Parp and increasing the expression level of BAX. 10b inhibited the epithelial-mesenchymal transition process by up-regulating E-cadherin and down-regulating N-cadherin. Furthermore, the tubulin polymerization inhibitory activity in vitro of 10b was 2.4 μM. In vivo anticancer assay, 10b effectively inhibited MGC-803 xenograft tumor growth without causing significant loss of body weight. These sulfanilamide-1,2,3-triazole hybrids as potent tubulin polymerization inhibitors might be used as promising candidates for cancer therapy.

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Funding

This work was supported by the fund of The First Affiliated Hospital of Zhengzhou University.

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Authors and Affiliations

  1. The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China

    Shewei Guo, Yingwei Zhen, Mengguo Guo, Longzhou Zhang & Guosheng Zhou

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  1. Shewei Guo
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  2. Yingwei Zhen
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  3. Mengguo Guo
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  4. Longzhou Zhang
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  5. Guosheng Zhou
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Correspondence to Shewei Guo.

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Guo, S., Zhen, Y., Guo, M. et al. Design, synthesis and antiproliferative evaluation of novel sulfanilamide-1,2,3-triazole derivatives as tubulin polymerization inhibitors. Invest New Drugs 36, 1147–1157 (2018). https://doi.org/10.1007/s10637-018-0632-7

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  • DOI: https://doi.org/10.1007/s10637-018-0632-7

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