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Synthesis and antitumor activity evaluation in vitro of 4-aminoquinazoline derivatives containing 1,3,4-thiadiazole

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Abstract

In order to search for new antitumor drugs with high efficiency and low toxicity, a series of novel 4-aminoquinazoline derivatives containing 1,3,4-thiadiazole group were designed, synthesized and evaluated for antiproliferative activity against four human cancer cell lines (H1975, PC-3, MCF-7 and HGC-27) using MTT assay in vitro. Among them, compound N-(5-((3,5-dichlorobenzyl)thio)-1,3,4-thiadiazol-2-yl)-2-((4-(phenylamino)quinazolin-2-yl)thio)acetamide (15o) showed good anti-tumor proliferation activity against four tested cancer cell lines, with IC50 values of 1.96 ± 0.15 μM to PC-3 cell. The antitumor activity was significantly better than that of gefitinib. Further mechanism studies showed that compound 15o inhibited the migration ability of PC-3 tumor cells in a concentration dependent and time-dependent manner, and blocked the cell cycle in S phase. At the same time, cell cloning experiment further proved that compound 15o significantly inhibited the colony formation of PC-3 cells, The inhibition rate was as high as 92% at 2.0 μM.

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Funding

This work was supported by the the National Natural Science Foundation of China (No. U21A20416) and Opening Fund from State Key Laboratory of Esophageal Cancer Prevention & Treatment (No. K2020000X).

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Authors and Affiliations

  1. School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, China

    Xiaojie Si, Honglin Dai, Chao Gao, Hao Wang, Lingling Chi, Zhangjie Wang, Limin Liu, Luye Zhang, Erdong Li, Jiaxin Zheng, Yaoyao Wang, Yu Ke, Hongmin Liu & Qiurong Zhang

  2. Collaborative Innovation Center of New Drug Research and Safety Evaluation of Henan Province, Zhengzhou, 450001, China

    Xiaojie Si, Honglin Dai, Chao Gao, Hao Wang, Lingling Chi, Zhangjie Wang, Limin Liu, Luye Zhang, Erdong Li, Jiaxin Zheng, Yaoyao Wang, Yu Ke, Hongmin Liu & Qiurong Zhang

  3. State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou, 450052, China

    Yu Ke & Hongmin Liu

  4. Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou, 450001, China

    Hongmin Liu & Qiurong Zhang

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  1. Xiaojie Si
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Correspondence to Yu Ke, Hongmin Liu or Qiurong Zhang.

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Si, X., Dai, H., Gao, C. et al. Synthesis and antitumor activity evaluation in vitro of 4-aminoquinazoline derivatives containing 1,3,4-thiadiazole. Med Chem Res 31, 1384–1392 (2022). https://doi.org/10.1007/s00044-022-02913-y

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  • DOI: https://doi.org/10.1007/s00044-022-02913-y

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