Novel synthetic acridine-based derivatives as topoisomerase Ⅰ inhibitors  

作　　者：Bin Li Chun-Mei Gao Qin-Sheng Sun Lu-Lu Li Chun-Yan Tan Hong-Xia Liu Yu-Yang Jiang 

机构地区：[1]Tsinghua University,Department of Chemistry [2]The Ministry-Province Jointly Constructed Base for State Key Lab-Shenzhen Key Laboratory of Chemical Biology [3]Shenzhen Anti-Tumor Drug Development Engineering Laboratory,the Graduate School at Shenzhen,Tsinghua University [4]School of Medicine,Tsinghua University

出　　处：《Chinese Chemical Letters》2014年第7期1021-1024,共4页中国化学快报（英文版）

基　　金：the Ministry of Science and Technology of the People’s Republic of China(Nos.2012AA020305and 2011DFA30620);the National Natural Science Foundation of China(Nos.21272134 and 21372141);Shenzhen Sci.&Tech.Bureau(No.JCYJ20120831165730905)for the financial supports

摘　　要：Novel DNA binding agents against topoisomerases are needed for effective treatment of cancers. A series of new acridine-based derivatives 7a-7d were synthesized and their antiproliferative activity against K562 and HepG-2 cell lines were evaluated. Compound 7c with pyridin-2-yl-methanamino group substituted at the C9 position of acridine showed good antitumor activity against both cell lines. The DNA-binding affinity of compound 7c was evaluated by UV-vis absorption spectra and fluorescence emission spectra. DNA topoisomerase I mediated relaxation of plasmid pBR322 DNA was also tested. Our results suggested that compound 7c with good antitumor activity and topoisomerase I inhibition activity can be developed as a prime candidate for further chemical optimization.Novel DNA binding agents against topoisomerases are needed for effective treatment of cancers. A series of new acridine-based derivatives 7a-7d were synthesized and their antiproliferative activity against K562 and HepG-2 cell lines were evaluated. Compound 7c with pyridin-2-yl-methanamino group substituted at the C9 position of acridine showed good antitumor activity against both cell lines. The DNA-binding affinity of compound 7c was evaluated by UV-vis absorption spectra and fluorescence emission spectra. DNA topoisomerase I mediated relaxation of plasmid pBR322 DNA was also tested. Our results suggested that compound 7c with good antitumor activity and topoisomerase I inhibition activity can be developed as a prime candidate for further chemical optimization.

关 键 词：ACRIDINE DNA binding agent TOPOISOMERASE ANTICANCER 

分 类 号：TQ253.26[化学工程—有机化工] TQ460.1