Synthesis and Antiproliferative Activity of 2,4,5,6-Tetrasubstituted Pyrimidine Derivatives Containing Anisole

被引：0

作者：

Gao Chao ^{[1
,2
]}

Si Xiaojie ^{[1
,2
]}

Chi Lingling ^{[1
,2
]}

Wang Hao ^{[1
,2
]}

Dai Honglin ^{[1
,2
]}

Liu Limin ^{[1
,2
]}

Wang Zhengjie ^{[1
,2
]}

Zhang Yang ^{[1
,2
]}

Wang Tao ^{[1
,2
]}

Zhou Yaochuan ^{[1
,2
]}

Zheng Jiaxin ^{[1
,2
]}

Ke Yu ^{[1
,2
,3
,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] Collaborat Innovat Ctr New Drug Res & Qual & Safe, Zhengzhou 450001, Peoples R China

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

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

来源：

CHINESE JOURNAL OF ORGANIC CHEMISTRY | 2022年 / 42卷 / 06期

基金：

中国国家自然科学基金;

关键词：

pyrimidine; anisole; synthesis; antiproliferative activity; INHIBITORS; ANALOGS; POTENT; RESISTANCE; AZD9291; DRUG;

D O I：

10.6023/cjoc202201048

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

In order to find efficient new anti-tumor drugs, a series of 2,4,5,6-tetrasubstituted pyrimidine derivatives containing anisole structure were designed, synthesized and evaluated for antiproliferative activity against four human cancer cell lines of PC-3, MGC-803, MCF-7 and HGC-27 using methyl thiazolyl tetrazolium (MTT) assay. Most of compounds displayed moderate to excellent antiproliferative activity against the four human tumor cell lines, among which the compound 5-ethyl-6((4-methoxyphenyl)thio)-N-4-(3,4,5-trimethoxyphenyl)pyrimidine-2,4-diamine (14t) showed the best antiproliferative activity on HGC-27 cells, with IC50 value of (0.98 +/- 0.12) mu mol.L-1, the antiproliferative activity is significantly better than that of the positive control 5-fluorouracil. Further research on anti-tumor mechanism showed that compound 14t could significantly inhibit the colony formation and migration of HGC-27 cells and induce apoptosis. At the same time, compound 14t can down-regulate the expression of anti-apoptotic protein Bcl-2 and up-regulate the expression of pro-apoptotic proteins Bax and P53.

引用

页码：1677 / 1686

页数：10

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