文献类型：期刊文献

英文题名：Novel metal complexes of naphthalimide-cyclam conjugates as potential multi-target receptor tyrosine kinase (RTK) inhibitors: Synthesis and biological evaluation

作者：Tan, Shaoying[1];Han, Kun[2];Li, Qiang[1];Tong, Linjiang[2];Yang, Yiqi[1];Chen, Zhuo[1];Xie, Hua[2];Ding, Jian[2];Qian, Xuhong[1];Xu, Yufang[1]

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

年份：2014

卷号：85

起止页码：207

外文期刊名：EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000342859700017)】；

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 (grants 21236002 and grants 21302054), the National Science & Technology Pillar Program, the Shanghai Committee of Science and Technology (Grant 13ZR1453100) and the Fundamental Research Funds for the Central Universities.

语种：英文

外文关键词：Metal complexes; Naphthalimide; Cyclam; RTK inhibitors; Antiproliferation; Antiangiogenesis

摘要：A novel series of metal complexes of naphthalimide-cyclam conjugates were synthesized and their in vitro antitumor activities were evaluated. The newly-synthesized compounds showed huge diversity of antiproliferative potency due to variety of metal ions and length of alkyl chains, among which the Zn(II) and Cr(III) complexes exhibited comparable antiproliferative activities with amonafide via multiple tyrosine kinase inhibition. Further research revealed that the representative compound 8a displayed broad-spectrum antiproliferative activity against 15 cancer cell lines with average IC50 value 10.18 +/- 3.25 mu M, and effective antiangiogenic activity on human microvascular endothelial cells (HMEC-1). In brief, metal complexes of naphthalimide-cyclam conjugates were firstly designed and synthesized as multi-target tyrosine kinase inhibitors and proved of their antitumor capacities. (C) 2014 Elsevier Masson SAS. All rights reserved.