Novel pyrazole-5-carboxamide and pyrazole-pyrimidine derivatives: Synthesis and anticancer activity

被引：100

作者：

Shi, Jing Bo ^{[1
]}

Tang, Wen Jian ^{[1
]}

Qi, Xing Bao ^{[1
]}

Li, Rong ^{[1
]}

Liu, Xin Hua ^{[1
,2
]}

机构：

[1] Anhui Med Univ, Sch Pharm, Hefei 230032, Peoples R China

[2] Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Jiangsu, Peoples R China

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2015年 / 90卷

基金：

中国国家自然科学基金;

关键词：

Synthesis; Pyrazole-5-carboxamide; Anticancer activity; Telomerase; POTENTIAL ANTITUMOR AGENTS; BIOLOGICAL EVALUATION; MOLECULAR DOCKING; TELOMERASE; INHIBITORS; DISCOVERY; CANCER; DESIGN; MOIETY; CELLS;

D O I：

10.1016/j.ejmech.2014.12.013

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of novel pyrazole-5-carboxamide and pyrazole-pyrimidine derivatives were designed and synthesized. All compounds have been screened for their antiproliferative activity against MGC-803, SGC-7901 and Bcap-37 cell lines in vitro. The results revealed that compounds 8a, 8c and 8e exhibited strong inhibitory activity against MGC-803 cell line. The flow cytometric analysis result showed that compound 8e could inhibit MGC-803 proliferation. Some title compounds were tested against telomerase, and compound 8e showed the most potent inhibitory activity with IC50 value at 1.02 +/- 0.08 mu M. The docking simulation of compound 8e was performed to get the probable binding model, among them, LYS 189, LYS 372, LYS 249 and ASP 254 may be the key residues for the telomerase activity. (C) 2014 Elsevier Masson SAS. All rights reserved.

引用

页码：889 / 896

页数：8

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