文献类型：期刊文献

英文题名：Naphthalimides exhibit in vitro antiproliferative and antiangiogenic activities by inhibiting both topoisomerase II (topo II) and receptor tyrosine kinases (RTKs)

作者：Wang, Xin[1];Chen, Zhuo[1,2];Tong, Linjiang[2];Tan, Shaoying[1];Zhou, Wei[1];Peng, Ting[2];Han, Kun[2];Ding, Jian[2];Xie, Hua[2];Xu, Yufang[1]

机构：[1]E China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai Key Lab Chem Biol, Shanghai Key Lab New Drug Design,Sch Pharm, Shanghai 200237, Peoples R China;[2]Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R China

年份：2013

卷号：65

起止页码：477

外文期刊名：EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000322850100046)】；

基金：This work is financially supported by the National Basic Research Program of China (973 Program, 2010CB126100), the National High Technology Research and Development Program of China (863 Program 2011AA10A207), the National Natural Science Foundation of China (Grant 81173080), the Shanghai Committee of Science and Technology (Grant 10431902600 and Grant 11DZ2260600), the Fundamental Research Funds for the Central Universities.

语种：英文

外文关键词：Angiogenesis; Multitarget; Naphthalimide; Topoisomerase II; Tyrosine kinase

摘要：Novel naphthalimide derivatives were designed and synthesized to modulate both topoisomerase II (topo II) and receptor tyrosine kinases (RTKs). Most target compounds exhibited effective and selective antiproliferative activities against three cancer cell lines by inhibiting topo II. The IC50 values ranged from 1.5 to 19.1 mu M. Moreover, compounds 8d and 12d moderately inhibited various angiogenesis-related RTKs, including FGFR1, VEGFR2 and PDGFR alpha. The representative compound 8d was then proved to possess antiangiogenic activity, which was evidenced by the inhibition of migration and tube formation activities of HMEC-1 cells. To our knowledge, it is the first time naphthalimides were identified as tyrosine kinases inhibitors (TKIs) besides their conventional cytotoxicity. (C) 2013 Elsevier Masson SAS. All rights reserved.