Synthesis and antiproliferative activity of 4-substituted-piperazine-1-carbodithioate derivatives of 2,4-diaminoquinazoline

被引：48

作者：

Cao, Sheng-Li ^{[1
,2
]}

Han, Ying ^{[1
]}

Yuan, Chong-Zhen ^{[2
,3
]}

Wang, Yao ^{[1
,2
]}

Xiahou, Zhi-Kai ^{[2
,3
]}

Liao, Ji ^{[2
,3
]}

Gao, Rui-Ting ^{[1
]}

Mao, Bei-Bei ^{[1
,2
]}

Zhao, Bao-Li ^{[1
]}

Li, Zhong-Feng ^{[1
]}

Xu, Xingzhi ^{[2
,3
]}

机构：

[1] Capital Normal Univ, Dept Chem, Beijing 100048, Peoples R China

[2] Capital Normal Univ, Beijing Key Lab DNA Damage Response, Beijing 100048, Peoples R China

[3] Capital Normal Univ, Coll Life Sci, Beijing 100048, Peoples R China

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2013年 / 64卷

基金：

中国国家自然科学基金;

关键词：

2,4-Diaminoquinazoline; Piperazine-1-carbodithioate; Synthesis; Antiproliferative activity; DNA damage; ANTIOPPORTUNISTIC INFECTION AGENTS; DNA-DAMAGE RESPONSE; THYMIDYLATE SYNTHASE; DIHYDROFOLATE-REDUCTASE; BIOLOGICAL EVALUATION; IN-VITRO; ANTITUMOR; INHIBITORS; ANALOGS; DESIGN;

D O I：

10.1016/j.ejmech.2013.04.017

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel series of 4-substituted-piperazine-1-carbodithioate derivatives of 2,4-diaminoquinazoline were synthesized and tested for their antiproliferative activities against five human cancer cell lines including A549 (lung cancer), MCF-7 (breast adenocarcinoma), HeLa (cervical carcinoma), HT29 and HCT-116 (colorectal cancer). Most of the synthesized compounds showed broad spectrum antiproliferative activity (IC50 1.47-11.83 mu M), of which 8f, 8m and 8q were the most active members with IC50 values in the range of 1.58-2.27, 1.84-3.27 and 1.47-4.68 mu M against five cancer cell lines examined, respectively. Further investigations revealed that compounds 8f, 8m and 8q exhibited weak inhibition against dihydrofolate reductase and no activity against thymidylate synthase, while induced DNA damage and activated the G2/M checkpoint in HCT-116 cells. (C) 2013 Elsevier Masson SAS. All rights reserved.

引用

页码：401 / 409

页数：9

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