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Chemical biology of MDR cancer selective cytotoxicity using natural product derivatives

Research Project

Project/Area Number 25670054
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Drug development chemistry
Research InstitutionKanazawa University

Principal Investigator

Goto Kyoko  金沢大学, 薬学系, 准教授 (50180245)

Co-Investigator(Renkei-kenkyūsha) TAMAI Ikumi  金沢大学, 医薬保健研究域薬学系, 教授 (20155237)
Research Collaborator GOTO Masuo  University of North Carolina at Chapel Hill, Eshelman School of Pharmacy, Research Professor
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywordsフラボノイド / TEDB / 多剤耐性がん / Collateral sensitivity / 多剤耐性がん細胞 / フラボノイド誘導体 / 異所性P-糖タンパク / 有糸分裂阻害効果
Outline of Final Research Achievements

TEDB, a derivative of natural flavonoid desmosdumotin B, selectively inhibits multidrug resistant (MDR) tumor cell growth without any cytotoxicity against normal cells as well as non-MDR cells. Despite its unique antiproliferative activity, the mechanism of action is totally unclear. Using medicinal chemistry as well as chemical biological approaches of TEDB derivatives, we have discovered that TEDB with an artificial benzothiophene ring-B system induced a unique antimitotic bioactivity. The resulting antimitotic agent showed a wide spectrum against multiple cancer cell lines including MDR cells. Based on this finding, a series of new antimitotic flavonoids was designed and synthesized. We have also identified a cellular protein overexpressed in MDR cells as a novel candidate for overcoming MDR tumor using TEDB derivatives.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (8 results)

All 2016 2015 2013 Other

All Int'l Joint Research (2 results) Journal Article (1 results) (of which Peer Reviewed: 1 results,  Acknowledgement Compliant: 1 results) Presentation (5 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Int'l Joint Research] ノースカロライナ大学/米国国立がん研究所(米国)

    • Related Report
      2015 Annual Research Report
  • [Int'l Joint Research] 国立台湾大学(台湾)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Development of a novel class of tubulin inhibitor from desmosdumotin B with a hydroxylated bicyclic B-ring2015

    • Author(s)
      Nakagawa-Goto K, Oda A, Hamel E, Ohkoshi E, Bastow KF, Lee KH, Goto M
    • Journal Title

      J Med Chem

      Volume: 58 Issue: 5 Pages: 2378-2389

    • DOI

      10.1021/jm501859j

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] ベンゾチオフェンフラボノイド誘導体の抗腫瘍活性と構造活性相関2016

    • Author(s)
      谷口由花子、釣本浩行、斎藤洋平、後藤益生、後藤(中川)享子
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-03-27
    • Related Report
      2015 Annual Research Report
  • [Presentation] TEDB-TB窒素置換誘導体の合成と抗腫瘍活性評価2016

    • Author(s)
      小林佑希子、斎藤洋平、後藤益生、後藤(中川)享子
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-03-27
    • Related Report
      2015 Annual Research Report
  • [Presentation] Benzothiophenyl flavones as new classes of mitotic inhibitors2015

    • Author(s)
      Taniguchi Y, Tsurimoto H, Saito Y, Hamel E, Goto M, Nakagawa-Goto K
    • Organizer
      250th ACS National Meeting & Exposition
    • Place of Presentation
      アメリカ、ボストン
    • Year and Date
      2015-08-16
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 新規抗腫瘍活性ベンゾチオフェンフラボノイドの合成と構造活性相関研究2015

    • Author(s)
      谷口由花子、釣本浩行、齋藤洋平、後藤益生、後藤(中川)享子
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      神戸
    • Year and Date
      2015-03-26 – 2015-03-28
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] TEDB-TB Analogs as New Classes of Tubulin Inhibitors2013

    • Author(s)
      後藤享子
    • Organizer
      第246回アメリカ化学会ナショナルミーティング
    • Place of Presentation
      インディアナポリス、アメリカ
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2022-02-16  

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