Hybrids of 1-deoxynojirimycin and aryl-1,2,3-triazoles and biological studies related to angiogenesis

被引:35
作者
Zhao, Yunxue [1 ,4 ]
Zhou, Ying [2 ,3 ]
O'Boyle, Kathy M. [1 ,4 ]
Murphy, Paul V. [2 ,3 ]
机构
[1] Univ Coll Dublin, UCD Sch Biomol & Biomed Sci, Dublin 4, Ireland
[2] Univ Coll Dublin, UCD Sch Chem & Chem Biol, Dublin 4, Ireland
[3] Univ Coll Dublin, Ctr Synth & Chem Biol, Dublin 4, Ireland
[4] Univ Coll Dublin, UCD Conway Inst, Dublin 4, Ireland
基金
爱尔兰科学基金会;
关键词
1-deoxynojirimycin; aryl-triazoles; angiogenesis; cell cycle; cyclin D1; inhibitor; cell migration; hybrid compounds;
D O I
10.1016/j.bmc.2008.05.012
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 [生物化学与分子生物学]; 081704 [应用化学];
摘要
Hybrids of 1-deoxynojirimycin (DNJ) and aryl-1,2,3-triazole have been synthesized with a view to identifying an inhibitor of both alpha-glucosidase and methionine aminopeptidase 2 (MetAP2). One compound was a potent inhibitor of alpha-glucosidase at both the enzyme and cellular level, and this agent also inhibited bovine aortic endothelial cell (BAEC) growth and tube formation. The anti-proliferative activity of this hybrid is due to its ability to induce cell-cycle arrest in the G(1) phase. The novel agent caused a reduction in the expression of cyclin D1 but did not promote apoptosis or inhibit the phosphorylation of ERK1/ 2. These observations indicate that its mechanism of action is distinct from fumagillin and its analogues, which inhibit MetAP2. Stress-fibre assembly in BAECs was abolished by the novel agent indicating that the inhibition of BAEC tube formation observed is partially a result of a reduction in cell motility. (c) 2008 Elsevier Ltd. All rights reserved.
引用
收藏
页码:6333 / 6337
页数:5
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