期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 89, 期 -, 页码 88-97出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2014.10.036
关键词
Hypoxia-inducible factor-1; Chalcone; Cancer; Invasion; Angiogenesis
资金
- National High Technology Research and Development Program of China (863 Program) [2012AA020305]
- Excellent Talents Plan in Liaoning Province [LJQ2014111]
- China Postdoctoral Science Foundation [20100481213, 2012T50474]
- Shenyang Pharmaceutical University Science Foundation [ZCJJ2013401]
A novel series of chalcone derivatives were synthesized and their biological activities against HIF-1 were evaluated. Among these compounds, 5d exhibited clearly inhibitory effects on HIF-1 by downregulating the expression of HIF-1 cc under hypoxic conditions. Meanwhile, it also significantly suppressed VEGF-induced migration and invasion of Hep3B and HUVEC cells in nontoxic concentrations. Additionally, tube formation assay demonstrated its anti-angiogenesis activity. Moreover, the in vivo study indicated that compound 5d could retard tumor growth of Hep3B xenograft models and reduced CD31 and MMP-2 expression in tumor tissues. Finally, in acute intravenous toxicity, 5d was well tolerated and was found to be non-toxic up to 200 mg/kg in Swiss mice. These findings support the further investigation on the anti-invasive and anti-angiogenic potential of this class of compounds as HIF-1 inhibitor. (C) 2014 Elsevier Masson SAS. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据