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Design, Synthesis and Antitumor Activity Evaluation of Trifluoromethyl-Containing Polysubstituted Pyrimidine Derivatives

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Abstract

Design and synthesis of two series of trifluoromethyl-containing polysubstituted pyrimidine derivatives in order to seek more effective anti-tumor drugs, and the antiproliferative activity of these compounds against four human tumor cell lines (PC-3, MGC-803, MCF-7, HGC-27) was evaluated by MTT method. Most of the compounds have moderate anti-proliferative activities, among which compounds (XXId) and (XXIe) have good selectivity for PC-3 cells. The IC50 (concentration required to achieve 50% inhibition of the tumor cell proliferation) values of compounds (XXId) and (XXIe) for PC-3 cell were 4.42 ± 0.46 μmol L–1 and 4.85 ± 0.59 μmol L–1, respectively, and their anti-proliferative activities were significantly better than that of the positive control 5-fluorouracil (6.39 ± 0.71 μmol L–1). Molecular docking results indicated that compounds (XXId) and (XXIe) were likely to be well integrated in the hydrophobic pocket of ubiquitin-specific protease 7 (USP7), which has the value of further research and development.

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Funding

This work was supported by the National Natural Sciences Foundation of China (no. 82020108030).

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Authors and Affiliations

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

    C. Lingling, W. Hao, Y. Fuqiang, G. Chao, D. Honglin, S. Xiaojie, Z. Yang, Z. Jiaxin, S. Lihong, L. Hongmin & Z. Qiurong

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

    C. Lingling, W. Hao, Y. Fuqiang, G. Chao, D. Honglin, S. Xiaojie, Z. Yang, Z. Jiaxin, S. Lihong, L. Hongmin & Z. Qiurong

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

    S. Lihong, L. Hongmin & Z. Qiurong

  4. Key Laboratory of Advanced Drug Preparation Technologie, Ministry of Education of China, 450052, Zhengzhou, China

    S. Lihong, L. Hongmin & Z. Qiurong

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  1. C. Lingling
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Lingling, C., Hao, W., Fuqiang, Y. et al. Design, Synthesis and Antitumor Activity Evaluation of Trifluoromethyl-Containing Polysubstituted Pyrimidine Derivatives. Russ J Bioorg Chem 49, 86–100 (2023). https://doi.org/10.1134/S1068162023010168

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