Chinese Journal of Organic Chemistry >
Synthesis and Antitumor Activity of 3-Hydrazone Quinazolinone Derivatives
Received date: 2022-06-02
Revised date: 2022-07-14
Online published: 2022-09-09
Supported by
National Undergraduate Training Program for Innovation and Entrepreneurship(2020033); National Nature Science Foundation of China(21867004); Guizhou Provincial Education Department(Qjh KY Zi[2021]041)
A series of 3-hydrazone quinazolinone derivatives were synthesized via introducing hydrazone structure into quinazolinone 3-position by active splicing principle. Their structures were confirmed by nuclear magnetic resonance spectroscopy (1H NMR, 13C NMR) and high resolution mass spectrometry (HRMS). The results of antitumor activity test showed that these compounds have effective inhibitory activity on A549, PC-3, HepG2 and K562 tumor cell lines. The IC50 value of (E)-N-((2-chloro-1-methyl-1H-indol-3-yl)methylene)-2-(7-fluoro-4-oxoquinazolin-3(4H)-yl)acetohydrazide (H1) on HepG2 was (9.90±1.13) μmol/L and (E)-2-(7-fluoro-4-oxoquinazolin-3(4H)-yl)-N-((2-morpholino-1-propyl-1H-indol-3-yl)methyl- ene)acetohydrazide (H2) on PC-3 was (10.70±0.78) μmol/L. The inhibitory activities were better than those of positive control drug gefitinib [IC50=(23.33±4.14) μmol/L, IC50=(12.02±5.39) μmol/L]. In order to explore the anti-tumor mechanism of these compounds, a series of cell biological experiments were set out on PC-3 cells with compound H2. The apoptosis and 4',6-diamidino-2-phenylindole (DAPI) staining experiments showed that the compound H2 could induce apoptosis in PC-3 cells, and the cell cycle experiment further demonstrated that the compound H2 arrested PC-3 cells in G0/G1 phase.
Key words： 3-hydrazone quinazolinone; antitumor activity; cell apoptosis; cell cycle; synthesis
Weiqin Liu , Lihui Shao , Chengpeng Li , Yayu Zou , Haitao Long , Yan Li , Qiangsheng Ge , Zhenchao Wang , Guiping Ouyang . Synthesis and Antitumor Activity of 3-Hydrazone Quinazolinone Derivatives[J]. Chinese Journal of Organic Chemistry, 2023 , 43(1) : 214 -222 . DOI: 10.6023/cjoc202206004
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