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A study on the interaction between macromolecules such as tyrosine kinase and small molecules

酪氨酸激酶等大分子与小分子相互作用的研究

基本信息

批准号：
15590474
负责人：
AKAHO Eiichi
金额：
$ 1.98万
依托单位：
Kobe Gakuin University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

We synthesized indole derivatives, and investigated the inhibition activity against protein tyrosine kinase (p60 c-Src). As a result, it was found that Compound 4 showed the strongest inhibition activity representing 1.34 μM IC_<50>. When we investigated the interaction between Compound 4 and the enzyme active site, it was shown that the strong interaction was exhibited between Compound 4 and the Lis 295 which is said to play an important role in the active site. We also synthesized 3-(substituted-benzylidene)-1,3-dihydro-indolin derivatives, and investigated the interaction between the synthesized derivatives and protein tyrosine kinase (p60 c-Src). It was found that inhibitory IC_<50> of Compound 12, 19. 13 represented 21.91, 21.20, 30.92 μM, respectively. These values are considered to be fairly well, although they are not in the best range. As for the docking simulation of those compounds, Compound 8, and 16 showed the strong affinity against the active site of the enzyme. Malaysian plant extract, Acalypha siamensis Olive. Ex Gage was obtained from collaborative researcher, and isolated each ingredient and the structure determination was performed by analytical instrument such as NMR, MS and so on. It was indicated that innovative compounds, Acalyphaser existed as chiral form of R, R, S or S, S, R. Docking simulation study between those compounds and protein tyrosine kinase (p60 c-Src) represented binding free energy of -5.97 kal/mol, and some showed the hydrogen bond against Hia58. It was extrapolated that IC_<50> values against human T-cell acute lymphoblastic leukemia (CCRF-HSB-2) and human oral epithermal carcinoma (KB) was 0.72 1.42 μM and 1.42 μM respectively.

我们合成了吲哚衍生物，并研究了其对蛋白酪氨酸激酶（p60 c-Src）的抑制活性。结果，发现化合物4显示出最强的抑制活性，代表1.34 μM IC_2<50>。当我们研究化合物4和酶活性位点之间的相互作用时，显示出化合物4和据说在活性位点中起重要作用的Lis 295之间表现出强相互作用。我们还合成了3-（取代亚苄基）-1，3-二氢吲哚啉衍生物，并研究了它们与蛋白酪氨酸激酶（p60 c-Src）的相互作用。发现<50>化合物12、19. 13分别代表21.91、21.20、30.92 μM。这些值被认为是相当好的，尽管它们不在最佳范围内。对于这些化合物的对接模拟，化合物8和16显示出对酶活性位点的强亲和力。马来西亚植物提取物，Acalypha siamensis橄榄。从合作研究者处获得Ex Gage，通过NMR、MS等分析仪器对各组分进行分离和结构鉴定，表明创新化合物Acalyphaser以R，R，S或S，S，R的手性形式存在。这些化合物与蛋白酪氨酸激酶（p60 c-Src）之间的对接模拟研究表示结合自由能为-5.97 kal/mol，并且一些化合物显示针对Hia 58的氢键。外<50>推抗人T细胞急性淋巴细胞白血病（CCRF-HSB-2）和人口腔上皮癌（KB）的IC_（1/2）分别为0.72、1.42 μM和1.42 μM。

项目成果

期刊论文数量（46）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A study of pharmacists' consciousness toward separation of medical practice from pharmaceutical dispensing

药师行医分离意识研究

DOI：
发表时间：
2003
期刊：
YAKUGAKU ZASSHI 123(3)
影响因子：
0
作者：
Eiichi AKAHO;Masako UCHINASHI;Akiko TSURUSAWA;Junko TOMINAGA;Shinichi HAYASHI
通讯作者：
Shinichi HAYASHI

Synthesis and anti-tyrosine kinase activity of 3-(substituted-benzylidene)-1,3-dihydro-indolin derivatives : investigation of their role against p60c-Src receptor tyrosine kinase with the application of receptor docking studies

3-(取代-亚苄基)-1,3-二氢吲哚啉衍生物的合成和抗酪氨酸激酶活性：应用受体对接研究研究其对p60c-Src受体酪氨酸激酶的作用