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Novel synthetic acridine-based derivatives as topoisomerase I inhibitors

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

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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

    • 通讯作者: Chun-Mei Gao,
    Yu-Yang Jiang,
  • 基金项目:

    Shenzhen Sci. & Tech. Bureau (No. JCYJ20120831165730905) for the financial supports. (No. JCYJ20120831165730905)

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.

English

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  • 收稿日期:  2013-12-25
  • 网络出版日期:  2014-03-05
通讯作者: 陈斌, bchen63@163.com
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