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

被引：4

作者：

Honglin, D. ^{[1
,2
]}

Chao, G. ^{[1
,2
]}

Xiaojie, S. ^{[1
,2
]}

Yutong, Z. ^{[1
,2
]}

Zhengjie, W. ^{[1
,2
]}

Limin, L. ^{[1
,2
]}

Tao, W. ^{[1
,2
]}

Luye, Z. ^{[1
,2
]}

Yang, Z. ^{[1
,2
]}

Qin, Y. ^{[1
,2
]}

Peirong, Z. ^{[1
,3
]}

Lihong, S. ^{[1
,2
,3
]}

Qiurong, Z. ^{[1
,2
,3
,4
]}

机构：

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

[2] Collaborat Innovat Ctr New Drug Res & Safety Eval, Zhengzhou 450001, Peoples R China

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

[4] State Key Lab Esophageal Canc Prevent & Treatment, Zhengzhou 450052, Peoples R China

来源：

RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY | 2022年 / 48卷 / 05期

基金：

中国国家自然科学基金;

关键词：

quinazoline derivatives; acrylamide; antitumor activity; synthesis; EGFR KINASE INHIBITORS; MOLECULAR DOCKING; FACILE SYNTHESIS; ANALOGS;

D O I：

10.1134/S1068162022050090

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 mu M), 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.

引用

页码：1089 / 1100

页数：12

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