Synthesis and Characterization of Pyrazoleanthrone Derivatives as Aurora A Kinase Inhibitors

doi:10.1007/s40242-013-3216-2

Chemical Research in Chinese Universities ›› 2013, Vol. 29 ›› Issue (6): 1098-1103.doi: 10.1007/s40242-013-3216-2

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Synthesis and Characterization of Pyrazoleanthrone Derivatives as Aurora A Kinase Inhibitors

SUN Xiao-xiao², SUN Tao⁴, WANG Tai-yi³, ZHANG Yan³, LIU Hui-juan⁴, WANG Quan³, NIU Guo-jun⁴, LIU Wei¹, ZHOU Hong-gang², YANG Cheng^2,4

1. College of Sciences, Tianjin University of Science and Technology, Tianjin 300457, P. R. China;
2. College of Pharmacy, Tianjin 300071, P. R. China;
3. College of Life Sciences, NanKai University, Tianjin 300071, P. R. China;
4. High Throughput Molecular Drug Discovery Center, Tianjin International Joint Academy of Biotechnology and Medicine, Tianjin 300457, P. R. China

Received:2013-05-13 Revised:2013-07-19 Online:2013-12-01 Published:2013-08-30
Contact: LIU Wei E-mail:liuwei2006@tust.edu.cn
Supported by:
Supported by the Tianjin Small and Meclium-sized Enterprise Technology Innovation Fund, China(No.11ZXCXSY03500).

Abstract

Abstract:

Aurora A is a cell cycle kinase linked to cancer. For the purpose of finding biologically active of novel compounds and providing new ideas for drug-design, we performed virtual screening in commercially available databases and got pyrazoleanthrone with promising inhibitory activity against Aurora A. Optimization of solvent accessible C7 position of pyrazoleanthrone made us get thirteen target compounds. These pyrazoleanthrone derivatives were evaluated by Aurora A inhibition assays in vitro. The results show that some target compounds could inhibit Aurora A kinase. Meanwhile, these title compounds were tested in vitro against hepatocellular carcinoma(HepG2) cells by the 3'-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) method, showing that most of them had inhibitory potency. The inhibition rate of compound 6h was about 80% against HepG2 cells, and the IC₅₀ value was 17.4 μmol/L, which would be considered for further study.

Key words: Pyrazoleanthrone, Aurora-A kinase, Inhibitor, Biological activity

SUN Xiao-xiao, SUN Tao, WANG Tai-yi, ZHANG Yan, LIU Hui-juan, WANG Quan, NIU Guo-jun, LIU Wei, ZHOU Hong-gang, YANG Cheng. Synthesis and Characterization of Pyrazoleanthrone Derivatives as Aurora A Kinase Inhibitors[J]. Chemical Research in Chinese Universities, 2013, 29(6): 1098-1103.

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Synthesis and Characterization of Pyrazoleanthrone Derivatives as Aurora A Kinase Inhibitors

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