Citation: Zhang Fan, Wu Dang, Wang Gao-Lei, Hou Shuang, Ou-Yang Ping, Huang Jin, Xu Xiao-Yong. Synthesis and biological evaluation of novel 1, 2, 3-benzotriazin-4-one derivatives as leukotriene A₄ hydrolase aminopeptidase inhibitors[J]. Chinese Chemical Letters, ;2017, 28(5): 1044-1048. doi: 10.1016/j.cclet.2016.12.014 shu

Synthesis and biological evaluation of novel 1, 2, 3-benzotriazin-4-one derivatives as leukotriene A₄ hydrolase aminopeptidase inhibitors

Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China

Corresponding author: Huang Jin, huangjin@ecust.edu.cn Xu Xiao-Yong, xyxu@ecust.edu.cn

Received Date: 8 September 2016
Revised Date: 4 November 2016
Accepted Date: 18 November 2016
Available Online: 15 May 2016

Figures(4)

A series of novel 1, 2, 3-benzotriazin-4-one derivatives were designed, synthesized and their inhibitory activities against leukotriene A₄ hydrolase aminopeptidase in vitro were evaluated. Many compounds showed moderate to good activities at the concentration of 10 μmol/L. Among them, compound Ⅳ-16 exhibited the highest inhibitory activity up to 80.6% with an IC₅₀ of 1.30 0.20 μmol/L. The compound Ⅳ-16 was also tested the proliferation inhibitory activities in THP1 human AML cell line and its binding model with LTA₄H enzyme by molecular docking was studied. It indicated that 1, 2, 3-benzotriazin-4-one was a promising scaffold for further study. The relationship between structure and inhibitory activity was also preliminarily discussed.
- 1, 2, 3-Benzotriazin-4-one,
- Leukotriene A₄ hydrolase,
- Aminopeptidase activity,
- In vitro,
- Aminopeptidase inhibitors
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Synthesis and biological evaluation of novel 1, 2, 3-benzotriazin-4-one derivatives as leukotriene A4 hydrolase aminopeptidase inhibitors

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通讯作者: 陈斌, bchen63@163.com

Synthesis and biological evaluation of novel 1, 2, 3-benzotriazin-4-one derivatives as leukotriene A₄ hydrolase aminopeptidase inhibitors