Citation: Bin Li, Chun-Mei Gao, Qin-Sheng Sun, Lu-Lu Li, Chun-Yan Tan, Hong-Xia Liu, Yu-Yang Jiang. Novel synthetic acridine-based derivatives as topoisomerase I inhibitors[J]. Chinese Chemical Letters, ;2014, 25(7): 1021-1024. doi: 10.1016/j.cclet.2014.03.028 shu

Novel synthetic acridine-based derivatives as topoisomerase I inhibitors

Bin Li ^a,b ,
Chun-Mei Gao ^b,c,, ,
Qin-Sheng Sun ^b ,
Lu-Lu Li ^b ,
Chun-Yan Tan ^b,c ,
Hong-Xia Liu ^b ,
Yu-Yang Jiang ^b,c,d,,

1.
a Tsinghua University, Department of Chemistry, 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 Shenzhen Anti-Tumor Drug Development Engineering Laboratory, the Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China;
4.
d School of Medicine, Tsinghua University, Beijing 100084, China

Corresponding author: Chun-Mei Gao, Yu-Yang Jiang,
Received Date: 25 December 2013
Available Online: 5 March 2014
Fund Project:

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.
- Acridine,
- DNA binding agent,
- Topoisomerase,
- Anticancer
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