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Design, Synthesis, and Antitumor Activity Evaluation of 2,4,6-Trisubstituted Quinazoline Derivatives Containing Acrylamide

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Abstract

In order to discover novel and effective anti-tumor drugs, a series of new 2,4,6-trisubstituted quinazoline derivatives containing acrylamide structure have been designed, synthesized and evaluated for their antitumor activity against six human tumor cell lines (PC-3, Eca-109, MGC-803, HGC-27, A549 and H1975) by MTT assay, and compound N-(3-((6-methoxy-2-((3-methylbenzyl)thio)quinazolin-4-yl)amino)phenyl)acrylamide displayed the best antiproliferative activity against PC-3 cells (IC50 = 1.28 ± 0.63 μM), which was better than the positive control Gefitinib. Further mechanism research showed that this compound could significantly inhibited the migration and colony formation of PC-3 cells. At the same time, this compound induced PC-3 cells apoptosis through increasing the expression of pro-apoptotic proteins Bax and p53 and down-regulating the anti-apoptotic protein Bcl-2. This compound could also bound tightly to the active pocket of EGFR. Collectively, our findings suggested that this compound deserves further reseach as a potent antitumor agent for cancer therapy.

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Funding

Project supported by the National Natural Science Foundation of China (no. 82020108030) 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

    D. Honglin, G. Chao, S. Xiaojie, Z. Yutong, W. Zhengjie, L. Limin, W. Tao, Z. Luye, Z. Yang, Y. Qin, Z. Peirong, S. Lihong & Z. Qiurong

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

    D. Honglin, G. Chao, S. Xiaojie, Z. Yutong, W. Zhengjie, L. Limin, W. Tao, Z. Luye, Z. Yang, Y. Qin, S. Lihong & Z. Qiurong

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

    Z. Peirong, S. Lihong & Z. Qiurong

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

    Z. Qiurong

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  1. D. Honglin
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Correspondence to S. Lihong or Z. Qiurong.

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Honglin, D., Chao, G., Xiaojie, S. et al. Design, Synthesis, and Antitumor Activity Evaluation of 2,4,6-Trisubstituted Quinazoline Derivatives Containing Acrylamide. Russ J Bioorg Chem 48, 1089–1100 (2022). https://doi.org/10.1134/S1068162022050090

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