文献类型：期刊文献

英文题名：Synthesis and antiproliferative activity of indolizine derivatives incorporating a cyclopropylcarbonyl group against Hep-G(2) cancer cell line

作者：Shen, Yong-Miao[1,2];Lv, Peng-Cheng[1];Chen, Wu[1];Liu, Peng-Gang[1];Zhang, Ming-Zhu[2];Zhu, Hai-Liang[1]

机构：[1]Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Peoples R China;[2]Shaoxing Univ, Inst Chem & Chem Engn, Shaoxing 312000, Peoples R China

年份：2010

卷号：45

期号：7

起止页码：3184

外文期刊名：EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

收录：SCI-EXPANDED(收录号：WOS:000278626400060)、、WOS

基金：This work was supported by the Jiangsu National Science Foundation (No. BK2009239), Anhui National Science Foundation (No. 070416274X), and Zhejiang Provincial Natural Science Foundation (Y4080395).

语种：英文

外文关键词：Indolizine derivatives; Antiproliferative activities; Hep-G2 cell line; EGFR; Structure-activity relationship; Docking simulations

外文摘要：Indolizine and annulated indolizine derivatives incorporating a cyclopropylcarbonyl group were synthesized in a one pot procedure by the tanden reactions of [3 + 2] cycloaddition of the corresponding N-ylide with electron deficient alkene. Seventeen indolizine derivatives were reported for the first time. All the compounds were examined for their antiproliferative activity against the human hepatocellular liver carcinoma (Hep-G2) cell line by MTT method. Among the compounds tested, 5a, 5d, 5g and 5j showed the most favorable activities with IC50 values of 0.39, 0.48, 0.29 and 0.20 mu g/mL. Especially, compound 5j displayed potent antiproliferative activities with IC50 value of 0.20 mu g/mL, and showed significant EGFR kinase inhibitory activity with IC50 value of 0.085 mu M. Docking simulations of 5j were carried out to illustrate the binding mode of the molecular into the EGFR active site. (C) 2010 Elsevier Masson SAS. All rights reserved.