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Design, Synthesis, and Antitumor Activity Evaluation of Trifluoromethyl-Substituted Pyrimidine Derivatives Containing Urea Moiety

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Abstract

In order to find efficient new antitumor drugs, a series of novel pyrimidine derivatives containing urea moiety were designed and synthesized, and the antitumor activity of four human tumor cells was evaluated by MTT analysis. The results showed that most of the target compounds exhibited moderate antitumor activity. In particular, the IC50 (concentration required to achieve 50% inhibition of the tumor cell proliferation) value of compound 2-((4-(4-ethylphenoxy)-6-(trifluoromethyl)pyrimidin-2-yl)thio)-N-((4-ethylphenyl)carba-moyl)acetamide for MGC-803 (human gastric carcinoma cell line) was 2.51 ± 0.17 µmol L–1, the anti-proliferative activity was significantly better than the positive control drug 5-fluorouracil. Molecular docking revealed that this compound can bind well to the active site of epidermal growth factor receptor (EGFR), and it may become a potential antitumor drug.

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Funding

Project supported by the National Natural Science Foundation of China (no. 81773562) and this work was supported by National Key Research Program of Proteins (no. 2018YFE0195100) and Openning 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, 450001, Zhengzhou, China

    Liu Limin, Wang Zhengjie, Liu Xiujuan, Gao Chao, Dai Honglin, Wang Tao, Li Na, Zhang Yang, Zhang Luye, Zheng Jiaxin, Shan Lihong, Liu Hongmin & Zhang Qiurong

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

    Liu Limin, Wang Zhengjie, Liu Xiujuan, Gao Chao, Dai Honglin, Wang Tao, Li Na, Zhang Yang, Zhang Luye, Shan Lihong, Liu Hongmin & Zhang Qiurong

  3. School of Pharmaceutical Sciences, Chian Pharmaceutical University, 210009, Nanjing, China

    Yan Heyi

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

    Zheng Jiaxin, Shan Lihong, Liu Hongmin & Zhang Qiurong

  5. State Key Laboratory of Esophageal Cancer Prevention and Treatment, 450052, Zhengzhou, China

    Liu Hongmin

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  1. Liu Limin
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Correspondence to Shan Lihong, Liu Hongmin or Zhang Qiurong.

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Liu Limin, Zhengjie, W., Xiujuan, L. et al. Design, Synthesis, and Antitumor Activity Evaluation of Trifluoromethyl-Substituted Pyrimidine Derivatives Containing Urea Moiety. Russ J Bioorg Chem 47, 1301–1311 (2021). https://doi.org/10.1134/S1068162021060157

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