中國醫藥大學機構典藏 China Medical University Repository, Taiwan:Item 310903500/927
English  |  正體中文  |  简体中文  |  全文笔数/总笔数 : 29490/55136 (53%)
造访人次 : 1997422      在线人数 : 429
RC Version 7.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
搜寻范围 查询小技巧：
  • 您可在西文检索词汇前后加上"双引号"，以获取较精准的检索结果
  • 若欲以作者姓名搜寻，建议至进阶搜寻限定作者字段，可获得较完整数据
    •  进阶搜寻
    主页 ‧ 登入 ‧ 上传 ‧ 说明 ‧ 关于CMUR ‧ 管理 到手机版


    jsp.display-item.identifier=請使用永久網址來引用或連結此文件: http://ir.cmu.edu.tw/ir/handle/310903500/927


    题名: 2-[氮-取代苄基]苯甲胺基-4-酮基-4,5-二氫呋喃-3-羧酸乙酯及類緣化合物之合成及其生理活性;Synthesis and Biological Activity of Ethyl 2- [N-substituted benzyl]benzylamino-4-oxo-4,5-dihydrofuran-3-carboxylate and related compounds
    作者: 李世良;Shih-Liang Li
    贡献者: 中國醫藥大學：藥物化學研究所碩士班
    关键词: 抗心律不整;抗活性氧化物;antiarrhythmics activity;Reactive oxygen species antagonist
    日期: 2007-06-21
    上传时间: 2009-08-13 09:37:21 (UTC+8)
    摘要: 著者合成了一系列2-[氮-取代苄基]苯甲胺基-4-酮基-4,5-二氫呋喃-3-羧酸乙酯及類緣化合物，且經各種圖譜資料予以確認之後，將所有合成經結構判定正確之化合物分別測試其抗心律不整與抗血管收縮活性以及抗活性氧化物、誘導細胞凋亡之活性及抗癌活性。
    在心律測試方面，化合物Ethyl 2-(N-o-fluorobenzyl)benzylamino- 4-oxo-4,5-dihydrofuran-3-carboxylate（6）、Ethyl 2-(N′-m-methylbenzyl) phenylhydrazino-4-oxo-4,5-dihydrofuran-3-carboxylate（21）在30μM抑制活性最強，呈現較佳之抑制活性，且不會抑制右心房自發性節律。而在強心測試方面，化合物在強心方面沒有比較好之藥理活性。
    利用fMLP（N-formyl-methionyl-leucyl-phenylalanine）對於人類嗜中性白血球會產生活性氧化物(ROS)，而測試不同藥物濃度對抗活性氧化物的抑制活性。目前測試結果發現，化合物Ethyl 2-phenylhydra- zino-4-oxo-4,5-dihydrofuran-3-carboxylate（12）對於人類嗜中性白血球之釋放活性氧化物(ROS)有最大的抑制作用( IC50 值為1.47μM)。
    在抗癌活性方面，以抑制百分之五十之癌症細胞的作用(IC50)來評估。從目前測試結果發現，以化合物Ethyl 2-phenylhydrazino-4-oxo-4,5- dihydrofuran-3-carboxylate（12）、Ethyl 2-(N′-m-fluorobenzyl)phenylhydra- zino-4-oxo-4,5-dihydrofuran-3-carboxylate（18）、Ethyl 2-(N′-p-fluoro- benzyl)phenylhydrazino-4-oxo-4,5-dihydrofuran-3-carboxylate（19）、Ethyl 2-(N′-m-nitrobenzyl)phenylhydrazino-4-oxo-4,5-dihydrofuran-3-
    carboxylate（26）、Ethyl 2-(N′-p-nitrobenzyl)phenylhydrazino-4-oxo-4,5- dihydrofuran-3-carboxylate (27)對於MDA-231（乳癌細胞）有細胞毒性，其IC50分別為12、13、12、12、11μM；而化合物（12）、（26）、(27)對於A549（肺癌細胞）具有細胞毒性，其IC50分別為11、9、13μM。

    部分藥理活性試驗仍在測試中，容待獲得測試結果後，即予以補上，並探討其結構與活性之關係。
    總結，改變苯胺結構對於抗心律不整活性與強心作用會降低，而具有抗癌與抗活性氧化物的活性是可以探討的。

    A series of ethyl 2- [N-substituted benzyl]benzylamino-4-oxo-4,5-dihydrofuran-3-carboxylate and related compounds has been synthesized and assigned by their spectra data. All of these synthetic compound were evaluated for biological activities(anti-arrhythmics activity、cardiovascular effect、Reactive oxygen species antagonist、induces apotosis、anticancer activite).
    Among the investigations of the inhibitory effect on the heart rate , Ethyl 2-(N-o-fluorobenzyl)benzylamino-4-oxo-4,5-dihydrofuran-3- carboxylate（6）、Ethyl 2-(N′-m-methylbenzyl)phenylhydrazino-4-oxo- 4,5-dihydrofuran-3-carboxylate（21）were found to exhibit the most significant activities at 30μM while exhibited better activities and no inhibitory effect on the pacemaker S.A. node. The results of the contra- ctivity had exhibited negative .
    In screen test on reactive oxygen species (ROS) release induced by fMLP（N-formyl-methionyl-leucyl-phenylalanine） in human neutrophil and test of resisting reactive oxygen species in different concentration. The test result shows that Ethyl 2-phenylhydrazino-4-oxo-4,5-dihydrofuran- 3-carboxylate（12）have the greatest influence against the reactive oxygen species release induced by fMLP in human neutrophil( IC50 =1.47μM).
    In anticancer activity, assess with suppressing 50% of the cancer cells (IC50). The test result shows that Ethyl 2-phenylhydrazino-4-oxo-4,5- dihydrofuran-3-carboxylate（12）、Ethyl 2-(N′-m-fluorobenzyl)phenylhydra- zino-4-oxo-4,5-dihydrofuran-3-carboxylate（18）、Ethyl 2-(N′-p-fluoro- benzyl)phenylhydrazino-4-oxo-4,5-dihydrofuran-3-carboxylate（19）、Ethyl 2-(N′-m-nitrobenzyl)phenylhydrazino-4-oxo-4,5-dihydrofuran-3-
    carboxylate（26）、Ethyl 2-(N′-p-nitrobenzyl)phenylhydrazino-4-oxo-4,5- dihydrofuran-3-carboxylate (27) demonstrated cytotoxicities for MDA-231（breast cancer）with IC50 values of 12、13、12、12、11μM, respectively.；（12）、（26）、(27) also demonstrated cytotoxicities for A549（lung cancer）with IC50 values of 11、9、13μM, respectively.
    Meanwhile, some of these synthetic compounds were still evaluated for their biological activity. Those results of biological activity will be reported later and discussed the relation of its structure and activate.
    In conclusion, anti-arrhythmia activation and cardiovascular effect to change the aniline structure,had to make to decrease activity, but can be probed into resisting cancer activation and activation of resisting the active oxide.
    显示于类别:[藥物化學研究所] 博碩士論文

    文件中的档案:

    档案 大小格式浏览次数
    index.html0KbHTML23检视/开启


    在CMUR中所有的数据项都受到原著作权保护.

    TAIR相关文章

     

    DSpace Software Copyright © 2002-2004  MIT &  Hewlett-Packard  /   Enhanced by   NTU Library IR team Copyright ©   - 回馈