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

Research Project

Project/Area Number 22659216
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Radiation science
Research InstitutionHirosaki University

Principal Investigator

KASHIWAKURA Ikuo  弘前大学, 大学院・保健学研究科, 教授 (00177370)

Co-Investigator(Kenkyū-buntansha) SAITO Yoko  弘前大学, 大学院・保健学研究科, 教授 (80225739)
MONZEN Satoru  弘前大学, 大学院・保健学研究科, 助教 (20514136)
Co-Investigator(Renkei-kenkyūsha) YOSHIZAWA Atsuhi  弘前大学, 大学院・理工学研究科, 教授 (30322928)
TAKAHASHI Kenji  鳥取大学, 農学部・獣医学科, 准教授 (00400143)
Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥3,250,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,300,000)
Keywords金属錯体液晶 / 造影剤 / MRI / 抗腫瘍効果
Research Abstract

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.

Report

(3 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • Research Products

    (11 results)

All 2012 2011 2010 Other

All Journal Article (8 results) (of which Peer Reviewed: 4 results) Remarks (3 results)

  • [Journal Article] Suppressive effects of liquid crystal compounds on the growth of the U937 cells2012

    • Author(s)
      J. Ishikawa, Y. Takahashi, M. Hazawa, A. Yoshizawa and I. Kashiwakura
    • Journal Title

      Cancer Cell Int

      Volume: 12(1) Pages: 3-3

    • Related Report
      2011 Final Research Report
  • [Journal Article] Suppressive effects of liquid crystal compounds on the growth of U937 human leukemic monocyte lymphoma cells2012

    • Author(s)
      I.Kashiwakura, et al.
    • Journal Title

      Cancer Cell Int

      Volume: 12 Issue: 1 Pages: 1-7

    • DOI

      10.1186/1475-2867-12-3

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Suppressive effects of liquid crystal compounds on the growth of the A549 human lung cancer cell line2011

    • Author(s)
      Y. Takahashi, K. Takahashi, M. Hazawa, A. Nishizawa, A. Yoshizawa and I. Kashiwakura
    • Journal Title

      Invest New Drugs

      Volume: 29(4) Pages: 659-665

    • Related Report
      2011 Final Research Report
  • [Journal Article] Liquid crystal-related compound-induced cell growth suppression and apoptosis in the chronic myelogenous leukemia K562 cell line2011

    • Author(s)
      Y. Fukushi, M. Hazawa, K. Takahashi, A. Yoshizawa and I. Kashiwakura
    • Journal Title

      Invest New Drugs

      Volume: 29(5) Pages: 827-832

    • Related Report
      2011 Final Research Report
  • [Journal Article] Supramolecular assembly composed of different mesogenic compounds possessing a ω-hydroxyalkyl unit exhibits suppressive effects on the A549 human lung cancer cell line2011

    • Author(s)
      Y. Takahashi, M. Hazawa, K. Takahashi, M. Sagisaka, I. Kashiwakura and A. Yoshizawa
    • Journal Title

      Med Chem Comm

      Volume: 2 Pages: 55-59

    • Related Report
      2011 Final Research Report
  • [Journal Article] Supramolecular assembly composed of different mesogenic compounds possessing a ω-hydroxyalkyl unit exhibits suppressive effects on the A549 human lung cancer cell line.2011

    • Author(s)
      I.Kashiwakura, et al.
    • Journal Title

      Med Chem Comm

      Volume: 2 Pages: 55-59

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Suppressive effects of liquid crystal compounds on the growth of the A549 human lung cancer cell line.2010

    • Author(s)
      I.Kashiwakura, et al.
    • Journal Title

      Invest New Drugs

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Liquid crystal-related compound-induced cell growth suppression and apoptosis in the chronic myelogenous leukemia K562 cell line.2010

    • Author(s)
      I.Kashiwakura, et al.
    • Journal Title

      Invest New Drugs

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Remarks]

    • URL

      http://www.hs.hirosaki-u.ac.jp/~kashiwakura/

    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://www.hs.hirosaki-u.ac.jp/~kashiwakura/2011result.html

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.hs.hirosaki-u.ac.jp-~kashiwakura/home.html

    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2016-04-21  

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