Suppr超能文献

血管生成抑制剂 N-(8-(3-乙炔基苯氧基)辛基-1-去氧野尻霉素的生物学研究。

Biological study of the angiogenesis inhibitor N-(8-(3-ethynylphenoxy)octyl-1-deoxynojirimycin.

机构信息

UCD School of Biomolecular and Biomedical Science and the UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4.

出版信息

Chem Biol Drug Des. 2010 Jun;75(6):570-7. doi: 10.1111/j.1747-0285.2010.00968.x.

Abstract

The alpha-glucosidase inhibitors N-methyl-1-deoxynojirimycin (MDNJ) and castanospermine have been shown to inhibit angiogenesis. A hybrid of 1-deoxynojirimycin (DNJ) and an aryl-1,2,3-triazole, which inhibits both an alpha-glucosidase and methionine aminopeptidase-2 (MetAP2), displayed properties associated with inhibition of angiogenesis (Bioorg. Med. Chem., 16, 2008, 6333-7). The biological evaluation of a structural analogue N-(8-(3-ethynylphenoxy)octyl-1-deoxynojirimycin is described herein. Although this alkyne derivative did not inhibit MetAP2, it inhibited a bacterial alpha-glucosidase, altered bovine aortic endothelial cell (BAEC) surface oligosaccharide expression and inhibited BAEC proliferation by inducing G1 phase cell cycle arrest. Experiments showed G1 arrest was attributable to the alpha-glucosidase inhibitor inducing an increase in p27(Kip1) expression and high phosphorylation of ERK1/2 without a reduction in cyclin D1. The DNJ derivative (0.1 mM) prevented capillary tube formation from bovine aortic endothelial cells, whereas DNJ or other analogues were unable to inhibit tube formation at the same concentration. Stress fiber assembly in bovine aortic endothelial cells was abolished, and BAEC migration was inhibited indicating the inhibition of tube formation by this derivative is partially a result of a reduction in cell motility. The agent also caused a reduction in secretion of MMP-2 from bovine aortic endothelial cells. Therefore, the new alpha-glucosidase inhibitor has a different mechanism by which it inhibits angiogenesis in vitro when compared with deoxynojirimycin, the deoxynojirimycin -triazole hybrid, N-methyl-1-deoxynojirimycin and castanospermine.

摘要

α-葡萄糖苷酶抑制剂 N-甲基-1-去氧野尻霉素(MDNJ)和瓜氨酸已被证明能抑制血管生成。1-去氧野尻霉素(DNJ)和芳基-1,2,3-三唑的混合物,既抑制α-葡萄糖苷酶又抑制蛋氨酸氨肽酶-2(MetAP2),表现出与抑制血管生成相关的特性(Bioorg. Med. Chem.,16,2008,6333-7)。本文描述了一种结构类似物 N-(8-(3-乙炔基苯氧基)辛基-1-去氧野尻霉素的生物学评价。尽管该炔烃衍生物不抑制 MetAP2,但它抑制了一种细菌α-葡萄糖苷酶,改变了牛主动脉内皮细胞(BAEC)表面寡糖的表达,并通过诱导 G1 期细胞周期阻滞抑制 BAEC 增殖。实验表明,G1 期阻滞归因于α-葡萄糖苷酶抑制剂诱导 p27(Kip1)表达增加和 ERK1/2 高度磷酸化,而 cyclin D1 没有减少。DNJ 衍生物(0.1mM)阻止牛主动脉内皮细胞形成毛细血管管腔,而 DNJ 或其他类似物在相同浓度下无法抑制管腔形成。牛主动脉内皮细胞中的应激纤维组装被废除,BAEC 迁移被抑制,表明该衍生物抑制管腔形成部分是由于细胞迁移减少。该试剂还导致牛主动脉内皮细胞中 MMP-2 的分泌减少。因此,与脱氧野尻霉素、脱氧野尻霉素-三唑杂合体、N-甲基-1-脱氧野尻霉素和瓜氨酸相比,这种新的α-葡萄糖苷酶抑制剂在体外抑制血管生成的机制不同。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验