Novel synthetic 9-benzyloxyacridine analogue as both tyrosine kinase and topoisomerase I inhibitor  

作　　者：Xu-Liang Lang Qin-Sheng Sun Yu-Zong Chen Lu-Lu Li Chun-Yan Tan Hong-Xia Liu Chun-Mei Gao Yu-Yang Jiang 

机构地区：[1]Department of Chemistry,Tsinghua University [2]The Ministry-Province Jointly Constructed Base for State Key Lab-Shenzhen Key Laboratory of Chemical Biology [3]Bioinformatics and Drug Design Group.Department of Pharmacy,Centre for Computational Science and Engineering [4]Shenzhen Anti-Tumor Drug Development Engineering Laboratory,The Graduate School at Shenzhen,Tsinghua University [5]School of Medicine,Tsinghua University

出　　处：《Chinese Chemical Letters》2013年第8期677-680,共4页中国化学快报（英文版）

基　　金：supports from the Ministry of Science and Technology of China(Nos. 2012ZX09506001-010,2012AA020305 and 2011DFA30620);the National Natural Science Foundation of China(Nos.21272134 and 20902053);Shenzhen Sci & Tech Bureau(No. JCYJ20120831165730905)

摘　　要：Multi-target agents against tyrosine kinases and topoisomerases are potentially useful for the effective treatment of cancers.Discovery of new multi-target scaffolds are important for developing such agents. A series of five novel acridine analogues,LXL 1-5,were synthesized and their antiproliferative activity against HepC-2 cell lines were evaluated,among which the 9-benzyloxyacridine analogue,LXL-5, showed inhibitory activity against tyrosine kinases,VEGFR-2 and Src.The results of UV-visible absorption spectra and fluorescence emission spectra,as well as DNA topoisomerase I inhibition assay, indicated topoisomerase I inhibitory activity.Our study suggested that acridine scaffold,previously shown to have no multi-target kinase and topoisomerase inhibitory activity,might be potentially developed as a multi-target inhibitor of tyrosine kinases and topoisomerase I.Multi-target agents against tyrosine kinases and topoisomerases are potentially useful for the effective treatment of cancers.Discovery of new multi-target scaffolds are important for developing such agents. A series of five novel acridine analogues,LXL 1-5,were synthesized and their antiproliferative activity against HepC-2 cell lines were evaluated,among which the 9-benzyloxyacridine analogue,LXL-5, showed inhibitory activity against tyrosine kinases,VEGFR-2 and Src.The results of UV-visible absorption spectra and fluorescence emission spectra,as well as DNA topoisomerase I inhibition assay, indicated topoisomerase I inhibitory activity.Our study suggested that acridine scaffold,previously shown to have no multi-target kinase and topoisomerase inhibitory activity,might be potentially developed as a multi-target inhibitor of tyrosine kinases and topoisomerase I.

关 键 词：Acridine Topoisomerases Tyrosine kinases Antitumor DNA-binding 

分 类 号：TQ464[化学工程—制药化工]