The development of multifunctional drug for magnetic resonance imaging diagnosis that uses metallic complex liquid crystal compound

金属络合物液晶化合物用于磁共振成像诊断的多功能药物的开发

基本信息

  • 批准号:
    22659216
  • 负责人:
  • 金额:
    $ 2.08万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
  • 财政年份:
    2010
  • 资助国家:
    日本
  • 起止时间:
    2010 至 2011
  • 项目状态:
    已结题

项目摘要

Focusing on the biological activities of liquid crystal compound (LC) and their magnetic and electric field orientation, the purpose of this study was to develop the novel metallic complex and apply as the diagnostic drug in magnetic resonance imaging.We revealed the following points.1. Two amphiphilic LCs were considered to delay S-phase progression in cell cycle of human leukemic monocyte lymphoma U937 cells, through inhibition of MCM2, cyclin A, cyclin B, CDK2, phospho-CDK1 (Tyr15) and Cdc25 expression.2. The phenylpyrimidine derivatives and cyanobiphenyl derivatives showed cytostatic effects, causing the suppression of cell growth through G1 phase arrest in A549 human lung cancer cells. One of the phenylpyrimidine derivatives inhibited A549 growth without any toxicity to normal fibroblasts.3. The biological activity of 16 liquid crystal-related compounds to a chronic myelogenous leukemia cell line, K562, was evaluated. As a result, two compounds, 2-(4-butoxyphenyl)-5-(4-hydroxyphenyl) pyrimidine and 2-{4-(4-hexyloxyphenyl) phenyl}-5-hydroxypyrimidine showed marked growth suppression of K562 cells at μM range. In addition, only the former compound induced the activation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase, and apoptosis of K562 cells.4. An equimolar mixture of 4-cyano-4'-(6-hydroxyhexyloxy) biphenyl (I-CN) and 4-methyl-oxy-4'-(6-hydroxyhexyloxy) biphenyl (I-OMe) exhibits larger suppressive effects on the growth of A549 human lung cancer cell line and shows higher ability to form thermotropic and lyotropic liquid-crystalline phases than I-CN or I-OMe.5. We are currently examining the development of novel metallic complex LCs which can be regulated by external stimulation by an electrical field or magnetic field for future pharmacological application.
本研究围绕液晶化合物的生物活性及其在磁场和电场中的取向性,开发新型的金属配合物,并将其应用于磁共振成像诊断药物,主要研究内容如下:1.结论:1.两种两亲性LC均能通过抑制MCM2、cyclin A、cyclin B、CDK2、磷酸化CDK1(Tyr15)和Cdc25的表达,延缓人白血病单核细胞淋巴瘤U937细胞S期进程.苯基嘧啶衍生物和氰基联苯衍生物显示出细胞生长抑制作用,通过在A549人肺癌细胞中的G1期阻滞引起细胞生长抑制。其中一种苯基嘧啶衍生物抑制A549细胞生长,对正常成纤维细胞无毒性.评价了16种液晶相关化合物对慢性粒细胞白血病细胞株K562的生物活性。结果表明,2-(4-丁氧基苯基)-5-(4-羟基苯基)嘧啶和2-{4-(4-己氧基苯基)苯基}-5-羟基嘧啶在μ M浓度范围内对K562细胞有明显的生长抑制作用。此外,只有前一种化合物能诱导p38丝裂原活化蛋白激酶和c-Jun N-末端激酶的活化,并诱导K562细胞凋亡. 4-氰基-4'-(6-羟基己氧基)联苯(I-CN)和4-甲氧基-4'-(6-羟基己氧基)联苯(I-OMe)的等摩尔混合物对A549人肺癌细胞株的生长具有更大的抑制作用,并且显示出比I-CN或I-OMe更高的形成热致液晶相和溶致液晶相的能力。我们目前正在研究开发新的金属络合物LC,其可以通过电场或磁场的外部刺激来调节,以用于未来的药理学应用。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Suppressive effects of liquid crystal compounds on the growth of the U937 cells
液晶化合物对U937细胞生长的抑制作用
  • DOI:
  • 发表时间:
    2012
  • 期刊:
  • 影响因子:
    5.8
  • 作者:
    J. Ishikawa;Y. Takahashi;M. Hazawa;A. Yoshizawa and I. Kashiwakura
  • 通讯作者:
    A. Yoshizawa and I. Kashiwakura
Liquid crystal-related compound-induced cell growth suppression and apoptosis in the chronic myelogenous leukemia K562 cell line
  • DOI:
    10.1007/s10637-010-9430-6
  • 发表时间:
    2011-10
  • 期刊:
  • 影响因子:
    3.4
  • 作者:
    Yukako Fukushi;M. Hazawa;Kenji Takahashi;A. Yoshizawa;I. Kashiwakura
  • 通讯作者:
    Yukako Fukushi;M. Hazawa;Kenji Takahashi;A. Yoshizawa;I. Kashiwakura
Suppressive effects of liquid crystal compounds on the growth of the A549 human lung cancer cell line
  • DOI:
    10.1007/s10637-010-9411-9
  • 发表时间:
    2011-08-01
  • 期刊:
  • 影响因子:
    3.4
  • 作者:
    Takahashi, Yuuka;Hazawa, Masaharu;Kashiwakura, Ikuo
  • 通讯作者:
    Kashiwakura, Ikuo
Supramolecular assembly composed of different mesogenic compounds possessing a ω-hydroxyalkyl unit exhibits suppressive effects on the A549 human lung cancer cell line
  • DOI:
    10.1039/c0md00126k
  • 发表时间:
    2011-01-01
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Takahashi, Yuuka;Hazawa, Masaharu;Yoshizawa, Atsushi
  • 通讯作者:
    Yoshizawa, Atsushi
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KASHIWAKURA Ikuo其他文献

KASHIWAKURA Ikuo的其他文献

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{{ truncateString('KASHIWAKURA Ikuo', 18)}}的其他基金

Protective effects of a combination of multiple pharmaceutical drugs on the survival of mice exposed to lethal ionizing radiation
多种药物组合对暴露于致命电离辐射的小鼠存活的保护作用
  • 批准号:
    24659553
  • 财政年份:
    2012
  • 资助金额:
    $ 2.08万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
The identification of factor (s) which regulate individual radiosensitivity of human hematopoietic stem/progenitor cells and its application
人造血干/祖细胞个体放射敏感性调节因子的鉴定及其应用
  • 批准号:
    21390336
  • 财政年份:
    2009
  • 资助金额:
    $ 2.08万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Placental/Umbilical cord blood-derived mesenchymal stem cell-likestroma cells support the hematopoietic recovery of X-irradiated human CD34+ cells
胎盘/脐带血来源的间充质干细胞样基质细胞支持 X 射线照射的人 CD34 细胞的造血恢复
  • 批准号:
    18390327
  • 财政年份:
    2006
  • 资助金额:
    $ 2.08万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
The study of therapy for radiation-induced thrombocytopenia by using ex vivo expanded-megakaryocyte prepared from auto hematopoietic stem cell.
自体造血干细胞体外扩增巨核细胞治疗放射引起的血小板减少症的研究。
  • 批准号:
    15591253
  • 财政年份:
    2003
  • 资助金额:
    $ 2.08万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Action of optimum cytokine for the recovery of X-irradiated human hematopoietic stem and progenitor cells
最佳细胞因子对 X 射线照射的人类造血干细胞和祖细胞恢复的作用
  • 批准号:
    12672115
  • 财政年份:
    2000
  • 资助金额:
    $ 2.08万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)

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    23K07211
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