Synthesis and biological evaluation of pyrazole derivatives containing thiourea skeleton as anticancer agents

被引：265

作者：

Lv, Peng-Cheng ^{[1
]}

Li, Huan-Qiu ^{[1
]}

Sun, Juan ^{[1
]}

Zhou, Yang ^{[1
]}

Zhu, Hai-Liang ^{[1
]}

机构：

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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2010年 / 18卷 / 13期

基金：

中国国家自然科学基金;

关键词：

Pyrazole derivatives; Thiourea; EGFR; Inhibitors; Anticancer; GROWTH-FACTOR RECEPTOR; ANTITUMOR-ACTIVITY; ANTIBACTERIAL ACTIVITY; HUMAN-BREAST; EXPRESSION; INHIBITORS; POTENT; DESIGN; CANCER; IDENTIFICATION;

D O I：

10.1016/j.bmc.2010.05.034

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：

Two series of pyrazole derivatives designing for potential EGFR kinase inhibitors have been discovered. Some of them exhibited significant EGFR inhibitory activity. Compound 3-(3,4-dimethylphenyl)-5-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide (C5) displayed the most potent EGFR inhibitory activity with IC50 of 0.07 mu M, which was comparable to the positive control erlotinib. Docking simulation was performed to position compound C5 into the EGFR active site to determine the probable binding model. Antiproliferative assay results indicating that some of the pyrazole derivatives own high antiproliferative activity against MCF-7. Compound C5 showed significant antiproliferative activity against MCF-7 with IC50 of 0.08 mu M. Therefore, compound C5 with potent inhibitory activity in tumor growth inhibition would be a potential anticancer agent. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：4606 / 4614

页数：9

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