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Design, synthesis and biological evaluation of novel 2,4,6-trisubstituted quinazoline derivatives as potential antitumor agents

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Abstract

In this study, a series of novel 2,4,6-trisubstituted quinazoline derivatives were designed, synthesized and biologically evaluated their antiproliferative activity against four human cancer cell lines (Eca-109, A549, PC-3 and MGC-803). The most of designed compounds showed considerable antiproliferative activity against the tested four cancer cell lines, while compound 28g displayed the best antiproliferative activity with the IC50 values of 1.95 μM and 2.46 μM against MGC-803 cells and Eca-109 cells, respectively. Further mechanism studies indicated that 28g significantly inhibited the cell migration and colony formation of MGC-803 cells. Besides, 28g also dose-dependently induced cellular apoptosis and cell cycle arrest at S phase in MGC-803 cells. Overall, all these studies suggested that 28g has the potential to act as a valuable lead compound for the development of antitumor agents.

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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

    Hao Wang, Tianci Wang, Lingling Chi, Fuqing Yu, Honglin Dai, Chao Gao, **aojie Si, Zhengjie Wang, Limin Liu, Peirong Zhao, Yingnan Zhu, Hongmin Liu & Qiurong Zhang

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

    Hao Wang, Tianci Wang, Lingling Chi, Fuqing Yu, Honglin Dai, Chao Gao, **aojie Si, Zhengjie Wang, Limin Liu, Yingnan Zhu, Hongmin Liu & Qiurong Zhang

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

    Peirong Zhao, Hongmin Liu & Qiurong Zhang

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

    Yingnan Zhu, Hongmin Liu & Qiurong Zhang

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

    Hongmin Liu & Qiurong Zhang

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  1. Hao Wang
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Wang, H., Wang, T., Chi, L. et al. Design, synthesis and biological evaluation of novel 2,4,6-trisubstituted quinazoline derivatives as potential antitumor agents. Med Chem Res 32, 1832–1850 (2023). https://doi.org/10.1007/s00044-023-03114-x

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