A series of novel 1,2,3-benzotriazin-4-one derivatives were designed,synthesized and their inhibitory activities against leulcotriene A4 hydrolase aminopeptidase in vitro were evaluated.Many compounds showed moderate ...A series of novel 1,2,3-benzotriazin-4-one derivatives were designed,synthesized and their inhibitory activities against leulcotriene 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 LTA_4H 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.展开更多
基金financially supported by the National Natural Science Foundation of China(No.21272071)the Fundamental Research Funds for the Central Universitiessupport from Shanghai Foundation of Science and Technology(No.15431902100)
文摘A series of novel 1,2,3-benzotriazin-4-one derivatives were designed,synthesized and their inhibitory activities against leulcotriene 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 LTA_4H 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.
