2. Academic Validation
  3. Novel leucine ureido derivatives as aminopeptidase N inhibitors using click chemistry

Novel leucine ureido derivatives as aminopeptidase N inhibitors using click chemistry

  • Bioorg Med Chem. 2018 Jul 23;26(12):3145-3157. doi: 10.1016/j.bmc.2018.04.041.
Jiangying Cao 1,  Chunhua Ma 2,  Jie Zang 1,  Shuai Gao 1,  Qianwen Gao 1,  Xiujie Kong 1,  Yugang Yan 1,  Xuewu Liang 1,  Qin'ge Ding 1,  Chunlong Zhao 1,  Binghe Wang 3,  Wenfang Xu 1,  Yingjie Zhang 4
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, PR China.
  • 2 School of Chemistry and Chemical Engineering, Henan Normal University, Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions of Ministry of Education, Xinxiang 453007, China.
  • 3 Department of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA.
  • 4 Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, PR China. Electronic address: zhangyingjie@sdu.edu.cn.
PMID: 29859750 DOI: 10.1016/j.bmc.2018.04.041
Abstract

The over-expression of Aminopeptidase N on diverse malignant cells is associated with the tumor angiogenesis and metastasis. In this report, one new series of leucine ureido derivatives containing the triazole moiety was designed, synthesized and evaluated as APN inhibitors. Among them, compound 13v showed the best APN inhibition with an IC50 value of 0.089 ± 0.007 μM, which was two orders of magnitude lower than that of bestatin (IC50 = 9.4 ± 0.5 μM). Compound 13v also showed dose-dependent anti-angiogenesis activities. Even at the lower concentration (10 μM), compound 13v presented similar anti-angiogenesis activity compared with bestatin at 100 μM in both the human umbilical vein endothelial cells (HUVECs) capillary tube formation assay and the rat thoracic aorta rings test. Moreover, compared with bestatin, 13v exhibited comparable, if not better in vivo anti-metastasis activity in a mouse H22 pulmonary metastasis model.

Keywords

Aminopeptidase N; Anti-angiogenesis; Anti-metastasis; CD13; Triazole.

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