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Design, Synthesis, and Anti-Tumor Activity Evaluation In Vitro of 4,6,7–Trisubstituted Quinazoline Derivatives Containing Acrylamide Group

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Abstract

Objective: In order to enrich the library of anti-tumor small molecule compounds, 19 compounds, with highly effective anti-tumor, have been designed and synthesized. Methods: MTT assay was used to detect the anti-proliferation activity of 19 compounds on four human tumor cell lines (PC-3, H1975, A549 and Eca-109). Cell cycle experiment, cell migration experiment, cell clone experiment and cell apoptosis experiment were used to study the anti-tumor mechanism of compound (XIVm). Results: The compound (XIVm) showed the strongest anti-tumor activity against the above four human tumor cells, especially against H1975 cells, with an IC50 value of 1.09 ± 0.04 μM, which was significantly lower than that of 5-fluorouracil (5-FU). The results of a variety of cell experiments showed that the compound (XIVm) significant anti-tumor activity, such as inhibiting the proliferation and migration of H1975 cells, arresting H1975 cells at G2/M phase, and inducing apoptosis in H1975 cells. Discussion: Slight changes in the R group can cause significant changes in the in vitro anti-tumor activity. And when R is a strong electron withdrawing group of cyano and trifluoromethyl, compound (XIVm) exhibits the strongest inhibitory effect, with an IC50 value of 1.09 ± 0.04 μM on H1975 cells. Conclusions: 19 compounds showed significant anti-tumor activity, and the compound (XIVm), with a strong electron withdrawing group of cyano and trifluoromethyl, showed the most significant effect, and the anti-proliferation and anti-migration effects of compound (XIVm) was further investigated.

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DATA AVAILABILITY

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

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

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Authors and Affiliations

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

    Gu Dongling, Yang Zichen, Wang Shihao, Chi Lingling, Yu Fuqiang, Wang Hao, Si Xiaojie, Gao Chao, Ke Yu, Liu Hongmin & Zhang Qiurong

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

    Gu Dongling, Yang Zichen, Wang Shihao, Chi Lingling, Yu Fuqiang, Wang Hao, Si Xiaojie, Gao Chao, Ke Yu, Liu Hongmin & Zhang Qiurong

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

    Liu Hongmin & Zhang Qiurong

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

    Ke Yu, Liu Hongmin & Zhang Qiurong

Authors
  1. Gu Dongling
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  2. Yang Zichen
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  3. Wang Shihao
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  4. Chi Lingling
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  5. Yu Fuqiang
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  6. Wang Hao
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  7. Si Xiaojie
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  8. Gao Chao
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  9. Ke Yu
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  10. Liu Hongmin
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  11. Zhang Qiurong
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Contributions

The authors GD, YZ, and WS—carried out the experiment, analyzed and interpreted the data, and wrote the manuscript. The authors CL, YF, and WH—contributed to sample preparation. The authors SX and GC—helped to supervise the data analysis. The authors KY, LH, and ZQ—supervised and defend the findings of this work and revised the manuscript.

Corresponding authors

Correspondence to Ke Yu, Liu Hongmin or Zhang Qiurong.

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Informed consent was not required for this article. No conflict of interest was declared by the authors.

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Dongling, G., Zichen, Y., Shihao, W. et al. Design, Synthesis, and Anti-Tumor Activity Evaluation In Vitro of 4,6,7–Trisubstituted Quinazoline Derivatives Containing Acrylamide Group. Russ J Bioorg Chem 50, 530–543 (2024). https://doi.org/10.1134/S1068162024020031

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