文献类型：期刊文献

英文题名：Antiproliferative and apoptosis-inducing activities of novel naphthalimide-cyclam conjugates through dual topoisomerase (topo) I/II inhibition

作者：Tan, Shaoying[1];Sun, Deheng[1];Lyu, Jiankun[1];Sun, Xiao[1];Wu, Fangshu[1];Li, Qiang[1];Yang, Yiqi[1];Liu, Jianxu[1];Wang, Xin[1];Chen, Zhuo[1];Li, Honglin[1];Qian, Xuhong[1];Xu, Yufang[1]

机构：[1]E China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab Chem Biol, State Key Lab Bioreactor Engn,Shanghai Key Lab Ne, Shanghai 200237, Peoples R China

年份：2015

卷号：23

期号：17

起止页码：5672

外文期刊名：BIOORGANIC & MEDICINAL CHEMISTRY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000360349900045)】；

基金：This work is financially supported by the Fundamental Research Funds for the Central Universities, the National Natural Science Foundation of China (Grants 21302054, 81222046, 21173076 and 81230076) (Z.C., H.L.), the Shanghai Committee of Science and Technology (Grants 14431902100, and 13ZR1453100) (Y.X., Z.C.), the Opening Fund of Shanghai Key Laboratory of Chemical Biology (Grant SKLCB-2012-05) (Z.C.), the National S&T Major Project of China (Grant 2013ZX09507004) and the 863 Hi-Tech Program of China (Grant 2012AA020308) (H.L.). H.L. is also sponsored by Shanghai Rising-Star Tracking Program (Grant 13QH1401100), Specialized Research Fund for the Doctoral Program of Higher Education (Grant 20130074110004) and Fok Ying Tung Education Foundation (Grant 141035).

语种：英文

外文关键词：Naphthalimide-cyclam conjugates; Antitumor agents; Topoisomerase I; Topoisomerase II; DNA intercalation; Apoptosis

摘要：A novel series of naphthalimide-cyclam conjugates were designed and synthesized. Among them, compounds 4c, 4d, 8c and 8d which bearing long lipophilic alkyl chains, displayed comparable or more potent cytotoxic activities against human tumor cell lines than amonafide. Furthermore, the four compounds were proved to possess strong inhibition against both topoisomerase I and II. The representative compound 8c exhibited moderate DNA intercalation activity. Molecular modeling studies identified the possible interaction of compound 8c with the molecular target by forming topoisomerase/DNA/drug ternary complex. Finally, derivatives with long lipophilic alkyl chains could efficiently induce apoptosis. (C) 2015 Published by Elsevier Ltd.