Citation: Xu-Liang Lang, Qin-Sheng Sun, Yu-Zong Chen, Lu-Lu Li, Chun-Yan Tan, Hong-Xia Liu, Chun-Mei Gao, Yu-Yang Jiang. Novel synthetic 9-benzyloxyacridine analogue as both tyrosine kinase and topoisomerase I inhibitor[J]. Chinese Chemical Letters, ;2013, 24(8): 677-680. shu

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

Xu-Liang Lang ^a,b ,
Qin-Sheng Sun ^b ,
Yu-Zong Chen ^c ,
Lu-Lu Li ^b ,
Chun-Yan Tan ^b,d ,
Hong-Xia Liu ^b ,
Chun-Mei Gao ^b,d,, ,
Yu-Yang Jiang ^b,d,e,,

1.
a Department of Chemistry, Tsinghua University, Beijing 100084, China;
2.
b The Ministry-Province Jointly Constructed Base for State Key Lab-Shenzhen Key Laboratory of Chemical Biology, Shenzhen 518055, China;
3.
c Bioinformatics and Drug Design Group, Department of Pharmacy, Centre for Computational Science and Engineering, 117543 Singapore, Singapore;
4.
d Shenzhen Anti-Tumor Drug Development Engineering Laboratory, The Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China;
5.
e School of Medicine, Tsinghua University, Beijing 100084, China

Corresponding author: Chun-Mei Gao, Yu-Yang Jiang,
Received Date: 12 March 2013
Available Online: 10 May 2013

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 HepG-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.
- Acridine,
- Topoisomerases,
- Tyrosine kinases,
- Antitumor,
- DNA-binding
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