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Design and Synthesis of the Artificial Luminescent Death Ligands Based on C3-Symmetric Cyclometalated Iridium Complexes for Selective Staining and Apoptosis Induction of Cancer Cells

Research Project

Project/Area Number 24890256
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field Chemical pharmacy
Research InstitutionTokyo University of Science

Principal Investigator

HISAMATSU Yosuke  東京理科大学, 薬学部, 助教 (80587270)

Project Period (FY) 2012-08-31 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsがん治療薬 / イリジウム錯体 / 燐光 / ペプチド / pHプローブ / イメージング / 細胞死 / 金属含有がん治療薬 / アポトーシス / TRAIL / デスリガンド / デスレセプター
Research Abstract

TNF-related apoptosis-inducing ligand (TRAIL) having a C3-symmetric homotrimeric structure induces the apoptosis in various tumor cells and tissues through the interaction with death receptor (DR) on cell surface. In this study, we have addressed the design and synthesis of new C3-symmetric tris-cyclometalated Ir complexes having dual activity both agonist activity for apoptosis induction and luminescent imaging of cancer cells.Staining experiments of Jurkat cell with Ir complex having the DR5 binding cyclic peptide suggested that green emission was localized on the cell membrane. Moreover, flow cytometer analysis suggested that the correlation between DR5 expressions of cancer cells (Jurkat cells, Molt-4 cells, K562 cells) and emission intensities derived from Ir complex. Optimizations of Ir complexes for improvement of their TRAIL-like activity are undergoing.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • Research Products

    (40 results)

All 2014 2013 2012

All Journal Article (5 results) (of which Peer Reviewed: 5 results) Presentation (35 results)

  • [Journal Article] Synthesis and Photochemical Properties of pH Responsive Tris-Cyclometalated Iridium(III) Complexes That Contain a Pyridine Ring on the 2-Phenylpyridine Ligand2014

    • Author(s)
      Akihiro Nakagawa, Yosuke Hisamatsu, Shinsuke Moromizato, Masahiro Kohno, Shin Aoki
    • Journal Title

      Inorganic Chemistry

      Volume: 53巻 Pages: 409-422

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] A Unique pH-Responsive Supramolecular Gel from a Novel Quadruple Zwitterion which Responds to both Acid and Base2013

    • Author(s)
      Yosuke Hisamatsu, Supratim Banerjee, M. B. Avinash, T. Govindaraju, Carsten Schmuck
    • Journal Title

      Angewandte Chemie International Edition

      Volume: 52巻 Pages: 12550-12554

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] A Unique pH-Responsive Supramolecular Gel from a Novel Quadruple Zwitterion which Responds to both Acid and Base2013

    • Author(s)
      Yosuke Hisamatsu, Supratim Banerjee, M. B. Avinash, T. Govindaraju, and Carsten Schmuck
    • Journal Title

      Angewandte Chemie International Edition

      Volume: 52 Issue: 48 Pages: 12550-12550

    • DOI

      10.1002/anie.201306986

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Design and Synthesis of a Luminescent Cyclometalated Iridium(III) Complex Having N,N-Diethylamino Group that Stains Acidic Intracellular Organelles and Induces Cell Death by Photoirradiation2012

    • Author(s)
      Shinsuke Moromizato, Yosuke Hisamatsu, Yasuki Matsuo, Toshihiro Suzuki, Ryo Abe, Shin Aoki
    • Journal Title

      Inorganic Chemistry

      Volume: 52巻 Pages: 12697-12706

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Design and Synthesis of Luminescent Cyclometalated Iridium(III) Complex Having N,N-Diethylamino Group that Stains2012

    • Author(s)
      Shinsuke Moromizato, Yosuke Hisamatsu,Yasuki Matsuo, Toshihiro Suzuki, Ryo Abe, Shin Aoki
    • Journal Title

      Inorganic Chemistry

      Volume: 51 Issue: 23 Pages: 12697-12706

    • DOI

      10.1021/ic301310q

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] 環状ペプチドを連結したC^<3->対称性トリスシクロメタレート型イリジウム錯体の設計・合成と人工デスリガンドとしての機能評価2014

    • Author(s)
      久松洋介,渋谷愛,田中裕志,鈴木希美,有安真也,鈴木利宙,安部良,青木伸
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      熊本
    • Related Report
      2013 Final Research Report
  • [Presentation] 環状ペプチドを連結した C3-対称性トリスシクロメタレート型イリジウム錯体の設計・合成と人工デスリガンドとしての機能評価2014

    • Author(s)
      久松 洋介,渋谷 愛,田中 裕志,鈴木 希美,有安 真也,鈴木 利宙,安部 良,青木 伸
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      熊本
    • Related Report
      2013 Annual Research Report
  • [Presentation] 二核亜鉛錯体と官能基化されたビルディングブロックの自己集積による超分子ホスファターゼの構築とリン酸加水分解活性2013

    • Author(s)
      青木伸、鈴木麻美、田中亮、Mohd Zulkefeli、久松洋介、城始勇
    • Organizer
      日本化学会第93春季年会
    • Related Report
      2013 Final Research Report
  • [Presentation] 青・緑・赤色発光性トリスシクロメタレート型イリジウム(III)錯体の設計・合成と発光挙動2013

    • Author(s)
      久松洋介、諸見里真輔、中川朗宏、神戸彩、青木伸
    • Organizer
      日本化学会第93春季年会
    • Related Report
      2013 Final Research Report
  • [Presentation] ピリジル基を導入したシクロメタレー2013

    • Organizer
      Medicinal Chemistry Symposium
    • Place of Presentation
      Taiwan
    • Related Report
      2013 Final Research Report
  • [Presentation] 複核亜鉛錯体と有機化合物の自己集積による超分子ホスファターゼの構築とビルディングブロック修飾の効果2013

    • Author(s)
      青木伸、Mohd Zulkefeli、鈴木麻美、田中亮、鈴木麻美、城始勇、久松洋介
    • Organizer
      第10回ホストゲスト化学シンポジウム
    • Related Report
      2013 Final Research Report
  • [Presentation] pH応答能を備えた赤色発光性シクロメタレート型イリジウム錯体の設計と合成2013

    • Author(s)
      神戸彩、諸見里真輔、久松洋介、河野雅弘、青木伸
    • Organizer
      第23回金属の関与する生体関連反応シンポジウム
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] Design and Synthesis of Luminescent Iridium Complexes as Photochemical and Biomedical Tools2013

    • Author(s)
      Shin Aoki, Yosuke Hisamatsu, Shinsuke Moromizato, Akihiro Nakagawa, Ai Shibuya, Aya Kando, Hiroshi Tanaka, Toshihiro Suzuki, and Ryo Abe
    • Organizer
      15th Asian Chemical Congress (15ACC)
    • Place of Presentation
      Singapore
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] Design and Synthesis of Artificial Dimetallic Catalysis Inspired by an Active Center of Alkaline Phosphatase2013

    • Author(s)
      Yuuya Miyazawa, Yosuke Hisamatsu, and Shin Aoki
    • Organizer
      2nd International Postgraduate Conference on Pharmaceutical Sciences 2013 (iPoPS 2013)
    • Place of Presentation
      Malaysia
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] C3^-対称性イリジウム錯体を中心骨格とするTRAIL様人工デスリガンドの設計・合成と活性評価2013

    • Author(s)
      渋谷愛,久松洋介,田中裕志,鈴木利宙,安部良,青木伸
    • Organizer
      第7回バイオ関連化学シンポジウム
    • Place of Presentation
      名古屋
    • Related Report
      2013 Final Research Report
  • [Presentation] Design, Synthesis and Biological Applications of Luminescent Cyclometalated Ir(III) Complexes2013

    • Author(s)
      Yosuke Hisamatsu, Aya Kando, Shinsuke Moromizato, Ai Shibuya, Hiroshi Tanaka, Akihiro Nakagawa, Toshihiro Suzuki, Ryo Abe and Shin Aoki, 鈴木利宙,安部良,青木伸
    • Organizer
      第57回日本薬学会関東支部大会
    • Place of Presentation
      東京
    • Related Report
      2013 Final Research Report
  • [Presentation] Development of Photochemical Devices for Diagnosis and Treatment of Cancer2013

    • Author(s)
      Shin Aoki, Shinya Ariyasu, Yosuke Hisamatsu, Shinsuke Moromizato, Ai Shibuya, Eita Watanabe, Toshihiro Suzuki, Masanori Hayase, and Ryo Abe
    • Organizer
      9th AFMC International Medicinal Chemistry Symposium
    • Place of Presentation
      Taiwan
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] C3-対称性シクロメタレート型イリジウム錯体を中心骨格に有するTRAIL様人工デスリガンドの設計・合成と活性評価,久松ト型イリジウム(III)錯体の設計・合成と発光2013

    • Author(s)
      久松洋介,渋谷愛,田中裕志,鈴木希美,特性,中川朗宏、久松洋介、青木伸
    • Organizer
      日本薬学会第133年会
    • Related Report
      2013 Final Research Report
  • [Presentation] 生体内金属イオンを中心とする自己集積三量体型人工デスリガンドの設計と合成2013

    • Author(s)
      鯉沼香織、宮田悠、久松洋介、有安真也、青木伸
    • Organizer
      第57回日本薬学会関東支部大会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] 非対称性超分子構築を目的とするビルディングブロックの設計・合成と分子集積の検討2013

    • Author(s)
      田中亮、鈴木麻美、久松洋介、青木伸
    • Organizer
      第57回日本薬学会関東支部大会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] シクロデキストリン及び亜鉛錯体を有するロタキサンの設計と合成2013

    • Author(s)
      大田麻人、田中智博、久松洋介、青木伸
    • Organizer
      第57回日本薬学会関東支部大会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] 位置選択的な置換基導入反応に基づくトリスシクロメタレート型イリジウム(III)錯体の合成・発光特性の制御と生物学的応用2013

    • Author(s)
      久松洋介,諸見里真輔,中川朗宏,神戸彩,渋谷愛,田中裕志,青木伸
    • Organizer
      錯体化学会第63回討論会
    • Place of Presentation
      沖縄
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] ピリジン環を導入したシクロメタレート型イリジウム(III)錯体の設計・合成とpH依存的発光特性2013

    • Author(s)
      中川朗宏,久松洋介,諸見里真輔,河野雅弘,青木伸
    • Organizer
      錯体化学会第63回討論会
    • Place of Presentation
      沖縄
    • Related Report
      2013 Final Research Report
  • [Presentation] C3-対称性イリジウム錯体を中心骨格とするTRAIL様人工デスリガンドの設計・合成と活性評価2013

    • Author(s)
      渋谷 愛,久松 洋介,田中 裕志,鈴木 利宙,安部 良,青木 伸
    • Organizer
      第7回バイオ関連化学シンポジウム
    • Place of Presentation
      名古屋
    • Related Report
      2013 Annual Research Report
  • [Presentation] Design, Synthesis and Biological Applications of Luminescent Cyclometalated Ir(III) Complexes2013

    • Author(s)
      Yosuke Hisamatsu, Aya Kando, Shinsuke Moromizato, Ai Shibuya, Hiroshi Tanaka, Akihiro Nakagawa, Toshihiro Suzuki, Ryo Abe and Shin Aoki
    • Organizer
      9th AFMC International Medicinal Chemistry Symposium
    • Place of Presentation
      Taiwan
    • Related Report
      2013 Annual Research Report
  • [Presentation] C3-対称性シクロメタレート型イリジウム錯体を中心骨格に 有する TRAIL 様人工デスリガンドの設計・合成と活性評価2013

    • Author(s)
      久松 洋介,渋谷 愛,田中 裕志,鈴木 希美,鈴木 利宙,安部 良,青木 伸
    • Organizer
      第57回日本薬学会関東支部大会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] ピリジン環を導入したシクロメタレート型イリジウム(III)錯体の設計・合成とpH依存的発光特性2013

    • Author(s)
      中川朗宏,久松洋介,諸見里真輔,河野雅弘,青木 伸
    • Organizer
      錯体化学会第63回討論会
    • Place of Presentation
      沖縄
    • Related Report
      2013 Annual Research Report
  • [Presentation] 青・緑・赤色発光性トリスシクロメタレート型イリジウム(III)錯体の設計・合成と発光挙動2013

    • Author(s)
      久松洋介・諸見里真輔・中川朗宏・神戸彩・青木伸
    • Organizer
      日本化学会第93春季年会(2013)
    • Place of Presentation
      滋賀県草津市
    • Related Report
      2012 Annual Research Report
  • [Presentation] ピリジン環を導入したシクロメタレート型イリジウム錯体の設計・合成とpH依存的発光特性2013

    • Author(s)
      中川 朗宏、久松洋介、諸見里 真輔、中川 朗宏、青木伸
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      神奈川県横浜市
    • Related Report
      2012 Annual Research Report
  • [Presentation] ピリジン環を導入した発光性シクロメタレート型イリジウム錯体の合成と発光特性2012

    • Author(s)
      中川朗宏、久松洋介、大和田紘喜、松生泰樹、大多和修平、諸見里真輔、青木伸
    • Organizer
      第62回有機合成化学協会関東支部シンポジウム
    • Place of Presentation
      千葉
    • Related Report
      2013 Final Research Report
  • [Presentation] C3-対称性イリジウム錯体を中心骨格とする人工デスリガンドの設計・合成と活性評価2012

    • Author(s)
      渋谷愛、大多和修平、大和田紘喜、鈴木利宙、安部良、久松洋介、有安真也、北村正典、安部良、青木伸
    • Organizer
      第62回有機合成化学協会関東支部シンポジウム
    • Related Report
      2013 Final Research Report
  • [Presentation] Development of Photochemical Devices for Diagnosis and Treatment of Cancer2012

    • Author(s)
      Shin Aoki, Shinya Ariyasu, Yosuke Hisamatsu, Shinsuke Moromizato, Ai Shibuyaa, Eita Watanabec, Toshihiro Suzuki, Masanori Hayase, Ryo Abe
    • Organizer
      1st International Postgraduate Conference on Pharmaceutical Sciences 2012
    • Related Report
      2013 Final Research Report
  • [Presentation] Design and Synthesis of pH-Responsive Luminescent Cyclometalated Iridium(III) Complex for Cell Imaging and Phototherapy2012

    • Author(s)
      Shinsuke Moromizato, Yosuke Hisamatsu, Toshihiro Suzuki, Ryo Abe, Shin Aoki
    • Organizer
      1st International Postgraduate Conference on Pharmaceutical Sciences 2012
    • Related Report
      2013 Final Research Report
  • [Presentation] pH応答性および酸素活性化能を有するシクロメタレート型イリジウム錯体の設計と合成2012

    • Author(s)
      諸見里真輔、久松洋介、松生泰樹、有安真也、鈴木利宙、安部良、青木伸
    • Organizer
      第62回配位化合物の光化学討論会
    • Related Report
      2013 Final Research Report
  • [Presentation] シクロメタレート型イリジウム錯体の位置選択的置換反応とそのバイオケミカルツールへの応用2012

    • Author(s)
      青木伸、久松洋介、諸見里真輔、渋谷愛、大多和修平、大和田紘喜、有安真也
    • Organizer
      第62回配位化合物の光化学討論会
    • Related Report
      2013 Final Research Report
  • [Presentation] Structure and Monophosphate Hydrolysis Activity of Supramolecular Complexes Formed by Self-Assembly of Various Diimide Compounds with Dimeric Zinc(II) Complex and Copper2012

    • Author(s)
      Shin Aoki, Mohd Zulkefeli, Asami Suzuki, Ryo Tanaka, Yosuke Hisamatsu, Motoo Shir
    • Organizer
      第62回錯体化学討論会
    • Related Report
      2013 Final Research Report
  • [Presentation] pH依存的な発光特性と細胞死誘導活性を備えたシクロメタレート型イリジウム錯体の設計と合成2012

    • Author(s)
      久松洋介、諸見里真輔、鈴木利宙、松生泰樹、安部良、青木伸
    • Organizer
      第62回錯体化学討論会
    • Related Report
      2013 Final Research Report
  • [Presentation] Design and Synthesis of Cyclometalated Iridium Complexes for Cell Imaging and Phototherapy2012

    • Author(s)
      Shin Aoki, Shinsuke Moromizato, Ai Shibuya, Shuhei Ohtawa, Yosuke Hisamatsu, Shinya Ariyasu, Toshihiro Suzuki, Ryo Abe
    • Organizer
      13th Tetrahedron Symposium, Asia Edition
    • Related Report
      2013 Final Research Report
  • [Presentation] 位置選択的な置換反応を用いた青・緑・赤色発光性シクロメタレート型イリジウム錯体(III)の設計と合成2012

    • Author(s)
      久松洋介、諸見里 真輔、中川 朗宏、青木伸
    • Organizer
      第38回反応と合成の進歩シンポジウム
    • Place of Presentation
      東京都
    • Related Report
      2012 Annual Research Report
  • [Presentation] pH依存的な発光特性と細胞死誘導活性を備えたシクロメタレート型イリジウム錯体の設計と合成2012

    • Author(s)
      久松 洋介、諸見里 真輔、鈴木 利宙、松生 泰樹、安部 良、青木 伸
    • Organizer
      第62回錯体化学討論会
    • Place of Presentation
      富山県富山市
    • Related Report
      2012 Annual Research Report

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Published: 2012-11-27   Modified: 2019-07-29  

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