标题:Design, Synthesis, and Biological Evaluation of Pyrazoline-Based Hydroxamic Acid Derivatives as AminopeptidaseN (APN) Inhibitors
作者:Cao, Jiangying; Zang, Jie; Ma, Chunhua; Li, Xiaoguang; Hou, Jinning; Li, Jin; Huang, Yongxue; Xu, Wenfang; Wang, Binghe; Zhang, Ying 更多
作者机构:[Cao, Jiangying; Zang, Jie; Ma, Chunhua; Li, Xiaoguang; Hou, Jinning; Li, Jin; Huang, Yongxue; Xu, Wenfang; Zhang, Yingjie] Shandong Univ, Sch Pharmac 更多
通讯作者:Xu, WF;Zhang, YJ
通讯作者地址:[Xu, WF; Zhang, YJ]Shandong Univ, Sch Pharmaceut Sci, Dept Med Chem, Jinan 250012, Shandong, Peoples R China.
来源:CHEMMEDCHEM
出版年:2018
卷:13
期:5
页码:431-436
DOI:10.1002/cmdc.201700690
关键词:aminopeptidase N; anti-angiogenesis; antitumor agents; inhibitors;; pyrazoline
摘要:AminopeptidaseN (APN) has been recognized as a target for anticancer treatment due to its overexpression on diverse malignant tumor cells and association with cancer invasion, metastasis and angiogenesis. Herein we describe the synthesis, biological evaluation, and structure-activity relationship study of two new series of pyrazoline analogues as APN inhibitors. Among these compounds, 5-(2-(2-(hydroxyamino)-2-oxoethoxy)phenyl)-3-phenyl-4,5-dihydro-1H-pyrazole-1-carboxamide (compound 13e) showed the best APN inhibition with an IC50 value of 0.16 +/- 0.02m, which is more than one order of magnitude lower than that of bestatin (IC50=9.4 +/- 0.5m). Moreover, compound 13e was found to inhibit the proliferation of diverse carcinoma cells and to show potent anti-angiogenesis activity. At the same concentration, compound 13e presents significantly higher anti-angiogenesis activity than bestatin in human umbilical vein endothelial cells (HUVECs) capillary tube formation assays. The putative binding mode of 13e in the active site of APN is also discussed.
收录类别:SCOPUS;SCIE
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-85042140112&doi=10.1002%2fcmdc.201700690&partnerID=40&md5=b8d4f4e434658e0d1ac7d3cc14707130
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