Design, synthesis and antitumor activity evaluation of 2,4,6-trisubstituted quinazoline derivatives containing piperidine moiety

被引：2

作者：

Dai, Honglin ^{[1
,2
]}

Yu, Fuqiang ^{[1
,2
]}

Wang, Hao ^{[1
,2
]}

Chi, Lingling ^{[1
,2
]}

Gao, Chao ^{[1
,2
]}

Si, Xiaojie ^{[1
,2
]}

Zhang, Yutong ^{[1
,2
]}

Qian, Zhuo ^{[1
]}

Zhao, Peirong ^{[2
,3
]}

Zhu, Yingnan ^{[2
,4
]}

Liu, Hongmin ^{[1
,2
,3
,4
]}

Zhang, Qiurong ^{[1
,2
,3
,4
]}

机构：

[1] Zhengzhou Univ, Sch Pharmaceut Sci, Zhengzhou 450001, Peoples R China

[2] Inst Drug Discovery & Dev, Zhengzhou 450001, Peoples R China

[3] Minist Educ, Key Lab Adv Drug Preparat Technol, Zhengzhou 450001, Peoples R China

[4] Coinnovat Ctr Henan Prov New Drug R&D & Preclin Sa, Zhengzhou 450001, Peoples R China

来源：

MEDICINAL CHEMISTRY RESEARCH | 2023年 / 32卷 / 10期

基金：

中国国家自然科学基金;

关键词：

Quinazoline; Synthesis; Derivatives; Anti-proliferation; CANCER-PATIENTS; INHIBITORS; DISCOVERY;

D O I：

10.1007/s00044-023-03119-6

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In this study, 35 novel 2,4,6-trisubstituted quinazoline derivatives were designed and synthesized, and their anti-tumor activity in vitro were preliminarily explored. Among them, compound 19n exhibited the best anti-proliferative activity against MGC-803 cells with an IC50 of 4.61 mu M. Further biological experiments showed that compound 19n could inhibit the cloning formation of MGC-803 cells. DAPI staining and apoptosis experiments showed that compound 19n could induce apoptosis of MGC-803 cells in a concentration-dependent manner, and the cell cycle experiment indicated that compound 19n could also arrest the MGC-803 cell cycle in G(0)/G(1) phase. In addition, the ADME datas of compound 19n was predicted and the potential target of compound 19n was explained through molecular docking [GRAPHICS] .

引用

页码：2176 / 2195

页数：20

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