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Development of Glycoconjugated Hybrid Metal Complexes toward Frontier Medicinal Treatment and Elucidation of their Biomechanism

Research Project

Project/Area Number 16350032
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Inorganic chemistry
Research InstitutionNara Women's University

Principal Investigator

YANO Shigenobu  Nara Women's University, Graduate School of Humanities and Sciences, Professor, 大学院人間文化研究科, 教授 (60011186)

Co-Investigator(Kenkyū-buntansha) OBATA Makoto  Nara Women's University, Graduate School of Humanities and Sciences, Research Associates, 大学院人間文化研究科, 助手 (70343267)
MORIMOTO Keiko  Nara Women's University Faculty of Human Life and Environment, Faculty of Human Life and Environment, Professor, 生活環境学部, 教授 (30220081)
Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥9,900,000 (Direct Cost: ¥9,900,000)
Fiscal Year 2006: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2005: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2004: ¥3,500,000 (Direct Cost: ¥3,500,000)
Keywordsmedicine / antifungal activity / growth inhibition / antitumor activity / sugar / thioglycoside / PDT / photosensitizer / 真菌 / 銀(I)錯体 / 核画像診断 / がん / ポルフィリン / 金属錯体 / フラーレン / 糖尿病 / インスリン
Research Abstract

Medicinal inorganic chemistry is a discipline of growing significance in both therapeutic and diagnostic medicine. The rapidly expanding field of glycobiology has had a positive impact on medicinal inorganic chemistry. Introduction a carbohydrate to a metal-binding ligand has the ability to reduce toxicity, and improve solubility and molecular targeting to a wide variety of metal-based drugs. Six palladium (II) complexes as cisplatin derivatives with a sugar unit have been prepared. The complexes have been tested for in vivo cytotoxicity against P388 cells implanted in mice. All of Pd compounds are apparently nontoxic. A T/C value of 120% was obtained for maltose derivative at the dose of 400 mg/kg, which indicates that the compound may be endowed with antitumor activity. Radiolabelled carbohydrates have found widespread utility in the field of nuclear medicine. Our work in this area has centered on the development of carbohydrate-appended ^<99m>Tc complexes utilizing the {^<99m>Tc(CO) … More _3}+ core. A glucosamine-coupled derivative with a 2,2-dipicolylamine binding unit has shown exceptional in vitro stability and imaging studies are on-going. Due to the overall positive charge on this molecule, neutral forms are being prepared in order to test the effects of charge on the localization of these carbohydrate-based imaging agents. Photodynamic therapy (PDT) is an effective and selective treatment for cancer. Eight tetrakis [3-or 4-(β-D-glycopyranosyloxy) phenyl] chlorins were synthesized by means of the Whitlock method with diimide reduction and purified by reversed-phase thin layer chromatography. The cellular uptake of the eight chlorins was evaluated in HeLa cells. All glycoconjugated chlorins showed higher cellular uptake than tetraphenylporphyrin tetrasulfonic acid (TPPS). The photocytotoxicity of these compounds towards HeLa cells was examined. These photosensitizers had no cytotoxicity in the dark. The results indicate that the photocytotoxicity is not related simply to cellular uptake. Silver (I) complexes received attention because of their often displayed antimicrobial activity. The reaction of tris (2-bromoethyl) amine hydrobromide with sugar thiols or thioacetates leads to the formation of novel carbohydrate substituted tripodal NS_3 ligands. Complexation with silver (I) ions gives stable complexes. The highly water soluble complexes formed from the unprotected ligands show a wide spectrum of effective antimicrobial activities and their use lowers the cytotoxic and antiproliferative activities compared to the free silver salts. The field of medicinal inorganic chemistry has benefited greatly from advances in ligand design, leading to the development of improved diagnostic and therapeutic agents. Opportunities for the design of new metal-based and metal-binding agents will arise. Less

Report

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (30 results)

All 2007 2006 2005 2004

All Journal Article (28 results) Book (2 results)

  • [Journal Article] Control of Intramolecular Ether Oxygen Coordination in the Crystal Structure of the Copper(II) Complexes with Dipicolylamine (DPA)-Derived Ligands2007

    • Author(s)
      Y.Mikata
    • Journal Title

      Eur. J. Inorg. Chem. 8

      Pages: 1143-1149

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Novel Oxygen Chirality Induced by Asymmetric Coordination of Oxygen Atom to a Metal Center in a Series of Sugar-pendant Dipicolylamine-Copper(II) Complexes2006

    • Author(s)
      Y.Mikata
    • Journal Title

      Inorg. Chem. 45

      Pages: 1543-1551

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Silver(I) complexes based on novel tripodal thioglycosides : synthesis, structure and antimicrobial activity2006

    • Author(s)
      M.Gottschaldt
    • Journal Title

      Tetrahedron 62

      Pages: 11073-11080

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Novel Oxygen Chirality Induced by Asymmetric Coordination of Oxygen Atom to a Metal Center in a Series of Sugar-pendant Dipicolylamine-Copper (II) Complexes2006

    • Author(s)
      Y.Mikata, Y.Sugai, M.Obata, M.Harada, S.Yano
    • Journal Title

      Inorg. Chem. 45

      Pages: 1543-1551

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Silver (I) complexes based on novel tripodal thioglycosides : synthesis, structure and antimicrobial activity2006

    • Author(s)
      M.Gottschaldt, A.Pfeifer, H.Gorls, M.Obata, S.Yano
    • Journal Title

      Tetrahedron 62

      Pages: 11073-11080

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Structure and photochemical properties of (μ-alkoxo)bis(μ-carboxylato)diruthenium complexes with naphtylacetate ligands2006

    • Author(s)
      M.Nakai
    • Journal Title

      Inorg. Chem. 45

      Pages: 1543-1551

    • Related Report
      2006 Annual Research Report
  • [Journal Article] The Methoxysubstituted TQEN Family of Fluorescent Zinc Sensors2006

    • Author(s)
      Y.Mikata
    • Journal Title

      Inorg. Chem. 45

      Pages: 9262-9268

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Diamagnetic-paramagnetic conversion of tris(2-pyridylthio)methyl copper(III) via a structural change from trigonal bipyramid to octahedron2006

    • Author(s)
      R.Santo
    • Journal Title

      Angew. Chem. Int. Ed. 45

      Pages: 7611-7614

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Carbohydrate-Appended 2,2'-Dipicolylamine Metal Complexes as Potential Imaging Agents2005

    • Author(s)
      T.Storr
    • Journal Title

      Inorg. Chem. 44

      Pages: 2698-2705

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Cellular Uptake and Photocytotoxicity of Glycoconjugated Chlorins in HeLa Cells2005

    • Author(s)
      S.Hirohara
    • Journal Title

      J. Photochem. Photobiol. B, Biology 78

      Pages: 7-15

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Synthesis and Insulin-mimetic Activities of Metal Complexes with 3-Hydroxypyridine-2-carboxylic Acid2005

    • Author(s)
      M.Nakai
    • Journal Title

      J. Inorg. Biochem. 6

      Pages: 1275-1282

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Carbohydrate-Appended 2,2'-Dipicolylamine Metal Complexes as Potential Imaging Agents2005

    • Author(s)
      T.Storr, Y.Sugai, C.A.Barta, Y.Mikata, M.J.Adam, S.Yano, C.Orvig
    • Journal Title

      Inorg. Chem. 44

      Pages: 2698-2705

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Cellular Uptake and Photocytotoxicity of Glycoconjugated Chlorins in HeLa Cells2005

    • Author(s)
      S.Hirohara, M.Obata, S.Ogata, C.Ohtsuki, S.Higashida, S.Ogura, I.Okura, M.Takenaka, H.Ono, YSugai, Y.Mikata, M.Tanihara, S.Yano
    • Journal Title

      J. Photochem. Photobiol. B, Biology 78

      Pages: 7-15

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Synthesis and Insulin-mimetic Activities of Metal Complexes with 3-Hydroxypyridine-2-carboxylic Acid2005

    • Author(s)
      M.Nakai, F.Sekiguchi, M.Obata, C.Ohtsuki, Y.Adachi, H.Sakurai, C.Orvig, D.R.Rehder, S.Yano
    • Journal Title

      J. Inorg. Biochem. 6

      Pages: 1275-1282

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Novel Carbohydrate-Appended Metal Complexes for Potential Use in Molecular Imaging 2005.2005

    • Author(s)
      T.Storr
    • Journal Title

      Chem.Eur.J. 11

      Pages: 195-203

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A Glucosamine-Dipicolylamine Conjugate of Tc-99m(I) and Re-186(I) for Use in Imaging and Therapy.2005

    • Author(s)
      T.Storr
    • Journal Title

      Dalton Transactions

      Pages: 654-655

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Carbohydrate-Appended 2,2'-Dipicolylamine Metal Complexes as Potential Imaging Agents.2005

    • Author(s)
      T.Storr
    • Journal Title

      Inorg.Chem. 44

      Pages: 2698-2705

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Cellular Uptake and Photocytotoxicity of Glycoconjugated Chlorins in HeLa Cells.2005

    • Author(s)
      S.Hirohara
    • Journal Title

      J.Photochem.Photobiol.B, Biology 78

      Pages: 7-15

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Synthesis and Insulin-mimetic Activities of Metal Complexes with 3-Hydroxypyridine-2-carboxylic Acid.2005

    • Author(s)
      M.Nakai
    • Journal Title

      J.Inorg.Biochem. 6

      Pages: 1275-1282

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Tetrakis(2-quinolinylmethyl)ethylenediamine (TQEN) as a new fluorescent sensor for zinc.2005

    • Author(s)
      Y.Mikata
    • Journal Title

      Dalton Transactions.

      Pages: 545-550

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Cellular Uptake and Photocytotoxieity of Clycoconjugated Chlorins in HeLa Cells2005

    • Author(s)
      S.Hirohara
    • Journal Title

      J.Photochem.Photobiol.B. Biology 78

      Pages: 7-15

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Synthesis, Structural Characterization, and Antitumor Activity of Palladium(II) Complexes Containing a Sugar Unit2004

    • Author(s)
      I.Brudzinska
    • Journal Title

      Bioorg. Med. Chem. Lett. 1410

      Pages: 2553-2536

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Synthesis Structural Characterization, and Antitumor Activity of Palladium (II) Complexes Containing a Sugar Unit2004

    • Author(s)
      I.Brudzinska, Y.Mikata, M.Obata, C.Ohtsuki, S.Yano
    • Journal Title

      Bioorg. Med. Chem. Lett. 14(10)

      Pages: 2533-2536

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Electro- and photochemical properties of (μ-alkoxo)bis(μ-carboxylato)diruthenium complex having two tetraphenylporphinato zinc(II) moieties2004

    • Author(s)
      M.Obata
    • Journal Title

      Dalton Transactions

      Pages: 3283-3287

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Cellular Uptake and Photocytotoxicity of Glycoconjugated Porphyrins in HeLa Cells2004

    • Author(s)
      S.Hirohara
    • Journal Title

      Photochem.Photobiol 80

      Pages: 301-308

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Synthesis, Structural Characterization, and Antitumor Activity of Pallaklium(II) Complexes Containing a Sugar Unit2004

    • Author(s)
      I.Brudzinska
    • Journal Title

      Bioorg.Med.Chem.Lett. 1410

      Pages: 253-2536

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Carbonyl Orientation Determines Regio- and Enantio-Selectivity in 1,2-/1,4- Reduction of an NAD Model Compound2004

    • Author(s)
      Y.Mikata
    • Journal Title

      Org.Lett. 43

      Pages: 2921-2924

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Control of Oxygen Atom Chirality and Chelate Ring Conformation by Protected/Free Sugar Hydroxyl Groups on Glucose-Pendant Dipicolylamine-Copper(II) Complexes Paint2004

    • Author(s)
      Y.Mikata
    • Journal Title

      Inorg.Chem. 43

      Pages: 4778-4780

    • Related Report
      2004 Annual Research Report
  • [Book] ゲノム情報による医療材料の設計と開発2006

    • Author(s)
      谷原正夫
    • Total Pages
      250
    • Publisher
      シーエムシー出版KK
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Book] 実験科学講座22巻「金属錯体、金属クラスター」2004

    • Author(s)
      矢野重信
    • Total Pages
      538
    • Publisher
      丸善KK
    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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