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Design, synthesis and antitumor activity evaluation of pyrimidine derivatives containing 4-hydroxypiperidine group

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Abstract

In the current study, a series of pyrimidine derivatives containing the 4-hydroxypiperidine group were designed and synthesized, and the antiproliferative activity of these compounds against four human tumor cell lines (MGC-803, PC-3, A549, H1975) was evaluated by MTT method in vitro. Most of the compounds have moderate anti-proliferative activities, among which compound 17i displayed the most excellent anti-proliferative activity, with IC50 value of 3.89 ± 0.57 µM against H1975 cell. Preliminary antitumor mechanism studies revealed that compound 17i could inhibit colony formation and cell migration of H1975 cells. Furthermore, compound 17i induced H1975 cells apoptosis in a dose-dependent manner and H1975 cell cycle arrest in S phase to inhibit cell proliferation. These results indicates that compound 17i could be a promising lead for further studies.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. U21A20416).

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Authors and Affiliations

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

    Lingling Chi, Hao Wang, Fuqiang Yu, Chao Gao, Honglin Dai, Limin Liu, Zhengjie Wang, Hongmin Liu & Qiurong Zhang

  2. Institute of Drug Discovery and Development, Zhengzhou, 450001, China

    Lingling Chi, Hao Wang, Fuqiang Yu, Chao Gao, Honglin Dai, Limin Liu, Zhengjie Wang, Yuze Dong, Hongmin Liu & Qiurong Zhang

  3. Center for Drug Safety Evaluation and Research, Zhengzhou, 450001, China

    Yuze Dong, Hongmin Liu & Qiurong Zhang

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

    Hongmin Liu & Qiurong Zhang

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

    Hongmin Liu & Qiurong Zhang

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  1. Lingling Chi
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Chi, L., Wang, H., Yu, F. et al. Design, synthesis and antitumor activity evaluation of pyrimidine derivatives containing 4-hydroxypiperidine group. Med Chem Res 32, 2125–2137 (2023). https://doi.org/10.1007/s00044-023-03076-0

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