• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Analysis of Target Molecular and Preparation of Molecular Probes for Neurotrophic Low-Molecular Natural Products

Research Project

Project/Area Number 16510172
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Living organism molecular science
Research InstitutionFaculty of Pharmaceutical Sciences, Tokushima Bunri University

Principal Investigator

FUKUYAMA Yoshiyasu  Tokushima Bunri University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (70208990)

Co-Investigator(Kenkyū-buntansha) ESUMI Tomoyuki  Tokushima Bunri University, Faculty of Pharmaceutical Sciences, Lecture, 薬学部, 講師 (50315264)
TAKAHASHI Hironobu  Tokushima Bunri University, Faculty of Pharmaceutical Sciences, Assistant, 薬学部, 助手 (90289314)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2005: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
Keywordsneurotrophic substance / neurite outgrowth promotion / Palladium-catalyzed reaction / honokiol / talaumidin / neovibsanin / PC12 cell / fluorescent probe / 神経細胞死保護活性 / アミロイドβ
Research Abstract

This research project has been carried out aiming at search for new neurotrophic natural products and synthesis of the three known active compounds, honokiol, neovibsanin an talaumidin as well as for clarifying their neurotrophic mechanism. The following results have been obtained.
(1)Screening natural products by using PC 12 cells has resulted in the discovery of five new active compounds, one of which is an ergosterol bearing an endoperoxide. This compound not only promotes significantly neurite outgrowth of PC 12, but also exhibits neurotrophic activity in the primary cultured rat cortical neurons. Another four neovibsanins have been isolated as neurotrophic substances from Viburnum sieboldii.
(2)Honokiol has been synthesized by palladium-catalyzed Suzuki-Miyaura cross coupling as a key reaction. The structure units that are essential for neurotrophic activity have been identified. Several fluorescent derivatives attached to luminous groups (7-MCA or NBD) at the 3'-position were synth … More esized and then the distribution in neurons using them was investigated. Consequently, it was found that the fluorescent derivatives penetrated into the neuron and concentrated on the connecting region to the neurite. The competitive experiment between honokiol and the fluorescent derivatives suggest that the fluorescent derivatives of honokiol are likely to interact at the same site in the neurons as honokiol. These results indicate that honokiol can penetrate into the neuron and interacts at some specific proteins such as the enzyme.
(3)The enantioselective synthesis of talaumidin has been accomplished by asymmetric Evans protocol, stereoselective hydroboration and highly controlled Firedel-Crafts arylation. This synthesis led to the conclusion of the absolute configuration of (2S,3S,4S,5S)-talaumidin, and allowed us to prepare its possible stereoisomers for structure-activity relationship.
(4)Applying tandem Pd-catalyzed Heck and Trost reactions towards a diene system has developed the construction of the cyclohexane ring core fused with a tetrahydrofuran ring. This new methodology will be used for synthesis of neovibsanins. Less

Report

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

    (43 results)

All 2005 2004 2003

All Journal Article (34 results) Book (6 results) Patent(Industrial Property Rights) (3 results)

  • [Journal Article] New Labdane Diterpenoids from Hyptis fasciculata.2005

    • Author(s)
      Yoshiyasu Fukuyama et al.
    • Journal Title

      Chem. Pharm. Bull. 53・12

      Pages: 1577-1579

    • NAID

      110004049480

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Synthetic Studies toward Merrilactone A : A Short Synthesis of AB Ring Motif.2005

    • Author(s)
      Yoshiyasu Fukuyama et al.
    • Journal Title

      Tetrahedron Lett. 46・33

      Pages: 7407-7410

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Rearranged Vibsane-type Diterpenes from Viburnum awabuki and Photochemical Reaction of Vibsanin B.2005

    • Author(s)
      Yoshiyasu Fukuyama et al.
    • Journal Title

      Chem. Pharm. Bull. 53・1

      Pages: 72-80

    • NAID

      10016651580

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Neurtrophic Effect of Magnolol in the Hippocampal CA1 Region of Senescence-Accelerated Mic (SAMP1).2005

    • Author(s)
      Yoshiyasu Fukuyama et al.
    • Journal Title

      Biol. Pharm. Bull. 28・9

      Pages: 1762-1765

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Neurotrophic Effects of 1,4,Diaryl-2,3-dimethyltetrahydrofuran Lignans.2005

    • Author(s)
      Yoshiyasu Fukuyama et al.
    • Journal Title

      Biol. Pharm. Bull 27・2

      Pages: 289-293

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Honokiol-induced Neurite Outgrowth Promotion Depends on Activation of Extracellular Signal-regulated Kinases (ERK1/2).2005

    • Author(s)
      Yoshiyasu Fukuyama et al.
    • Journal Title

      Eur. J. Pharmcol 516・2

      Pages: 112-117

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] New Labdane Diterpenoids from Hyptis fasciculata.2005

    • Author(s)
      Y.Fukuyama et al.
    • Journal Title

      Chem.Pharm.Bull. 53, 12

      Pages: 1577-1579

    • NAID

      110004049480

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Synthetic Studies toward Merrilactone A : A Short Synthesis of AB Ring Motif.2005

    • Author(s)
      Y.Fukuyama et al.
    • Journal Title

      Tetrahedron Lett. 46, 33

      Pages: 7407-7410

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cytotoxic Limnoids from the Fruits of Brazilian Melia azedarach.2005

    • Author(s)
      Y.Fukuyama et al.
    • Journal Title

      Chem.Pharm.Bull. 53, 10

      Pages: 1362-1365

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Neurtrophic Effect of Magnolol in the Hippocampal CAI Region of Senescence-Accelerated Mic (SAMP1).2005

    • Author(s)
      Y.Fukuyama et al.
    • Journal Title

      Biol.Pharm.Bull. 28, 9

      Pages: 1762-1765

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Protective Effect of 5-Lipoxygenase Inhibitor Ardisiaquinone A on Hepatic Ischemia-reperfusion Injury in Rats.2005

    • Author(s)
      Y.Fukuyama et al.
    • Journal Title

      Planta Medica 71

      Pages: 717-720

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Honokiol-induced Neurite Outgrowth Promotion Depends on Activation of Extracellular Signal-regulated Kinases (ERK1/2).2005

    • Author(s)
      Y.Fukuyama et al.
    • Journal Title

      Eur.J.Pharmcol. 516, 2

      Pages: 112-117

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Neurotrophic Effects of 1,4,Diary1-2,3-dimethyltetrahydrofuran lignans.2005

    • Author(s)
      Y.Fukuyama et al.
    • Journal Title

      Biol.Pharm.Bull. 27(2)

      Pages: 289-293

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Rearranged Vibsane-type Diterpenes from Viburnum awabuki and Photochemical Reaction of Vibsanin B.2005

    • Author(s)
      Y.Fukuyama et al.
    • Journal Title

      Chem.Pharm.Bull. 53(1)

      Pages: 72-80

    • NAID

      10016651580

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cytotoxic Iridoid Aldehydes from Taiwanese Viburnum luzunicum.2005

    • Author(s)
      Y.Fukuyama et al.
    • Journal Title

      Chem.Pharm.Bull. 53(1)

      Pages: 125-127

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] New Labdane Diterpenoids from Hyptis fasciculata.2005

    • Author(s)
      Yoshiyasu Fukuyama et al.
    • Journal Title

      Chem.Pharm.Bull. 53・12

      Pages: 1577-1579

    • NAID

      110004049480

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Rearranged Vibsane-type Diterpenes from Viburnum awabuki and Photochemical Reaction of Vibsanin B.2005

    • Author(s)
      Yoshiyasu Fukuyama et al.
    • Journal Title

      Chem.Pharm.Bull. 53・1

      Pages: 72-80

    • NAID

      10016651580

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Neurtrophic Effect of Magnolol in the Hippocampal CA1 Region of Senescence-Accelerated Mic (SAMP1).2005

    • Author(s)
      Yoshiyasu Fukuyama et al.
    • Journal Title

      Biol.Pharm.Bull. 28・9

      Pages: 1762-1765

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Neurotrophic Effects of 1,4,Diaryl-2,3-dimethyltetrahydrofuran Lignans.2005

    • Author(s)
      Yoshiyasu Fukuyama et al.
    • Journal Title

      Biol.Pharm.Bull 27・2

      Pages: 289-293

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Honokiol-induced Neurite Outgrowth Promotion Depends on Activation of Extracellular Signal-regulated Kinases (ERK1/2).2005

    • Author(s)
      Yoshiyasu Fukuyama et al.
    • Journal Title

      Eur.J.Pharmcol 516・2

      Pages: 112-117

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Iridoid Glucosides and p-Coumaroyl Iridoids from Viburnum zunonicum and Their Cytotoxicity.2004

    • Author(s)
      Y.Fukuyama et al.
    • Journal Title

      J.Nat.Prod. 67(11)

      Pages: 1833-1838

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Efficient Synthesis of Isoplagiochin D, a Macrocyclic Bis(bibenzyl), by utilizing an Intramolecular Suzuki-Miyaura Reaction.2004

    • Author(s)
      Y.Fukuyama et al.
    • Journal Title

      Tetrahedron Left. 45(37)

      Pages: 6941-6945

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] New Ring C-seco Limonoids from Brazilian Melia azedarach and Their Cytotoxic Activity.2004

    • Author(s)
      Y.Fukuyama et al.
    • Journal Title

      J.Nat.Prod. 67(9)

      Pages: 1544-1547

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Neurotrophic Effects of Talaumdin, from Aristolochia arcuata, in Primary Cultured Rat Cortical Neurons.2004

    • Author(s)
      Y.Fukuyama et al.
    • Journal Title

      Planta Med. 70(7)

      Pages: 598-602

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Efficient Synthesis and Structure-activity Relationship of Honokiol, a Neurotrophic Biphenyl Neolignan.2004

    • Author(s)
      Y.Fukuyama et al.
    • Journal Title

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

      Pages: 2621-2625

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cyclovibsanins, Unprecedented Vibsane-type Diterpenes from Viburnum awabuki.2004

    • Author(s)
      Y.Fukuyama et al.
    • Journal Title

      Letters in Organic Chemistry 1(2)

      Pages: 189-193

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] TMC-95A, a Reversible Protosame Inhibitor, Induce Neurite Outgrowth in PC12 Cells.2004

    • Author(s)
      Y.Fukuyama et al.
    • Journal Title

      Bioorg.Med.Chem.Lett. 14(3)

      Pages: 63-665

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Seven Novel seco-Prezizaane-type Sesquiterpenes from the Pericarps of Illicium merrillianum.2004

    • Author(s)
      Y.Fukuyama et al.
    • Journal Title

      Chem.Pharm.Bull. 52(1)

      Pages: 104-107

    • NAID

      110003615484

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] TMC-95A, a Reversible Protosame Inhibitor, Induce Neurite Outgrowth in PC12 Cells2004

    • Author(s)
      Yoshiyasu Fukuyama et al.
    • Journal Title

      Bioorg.Med.Chem.Lett. 14・3

      Pages: 663-665

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Cyclovibsanins, Unprecedented Seven-Membered Vibsane-type Diterpenoids from Viburnum awbuki.2004

    • Author(s)
      Yoshiyasu Fukuyama et al.
    • Journal Title

      Letters in Organic Chemistry 1・2

      Pages: 189-193

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Efficient Synthesis and Structure-activity Relationship of Honokiol, a Neurotrophic Biphenyl Neolignan.2004

    • Author(s)
      Yoshiyasu Fukuyama et al.
    • Journal Title

      Bioorg.Med.Chem.Left. 14・10

      Pages: 2621-2625

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Neurotrophic Effects of Talaumdin, a Neoliganan from Aristolochia arcuata, in Primary Cultured Rat2004

    • Author(s)
      Yoshiyasu Fukuyama et al.
    • Journal Title

      Planta Medica 70・7

      Pages: 598-602

    • Related Report
      2004 Annual Research Report
  • [Journal Article] New Ring C-seco Limonoids from Brazilian Melia azedarach and Their Cytotoxic Activity.2004

    • Author(s)
      Yoshiyasu Fukuyama et al.
    • Journal Title

      J.Nat.Prod. 67・9

      Pages: 1544-1547

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Efficient Synthesis of Isoplagiochin D, a Macrocyclic Bisbibenzyl, by utilizing Pd(0)-catalyzed Marcocylization.2004

    • Author(s)
      Yoshiyasu Fukuyama et al.
    • Journal Title

      Tetrahedron Letters 45・37

      Pages: 6941-6945

    • Related Report
      2004 Annual Research Report
  • [Book] Studies in Natural Products Chemistry, Vol. 322005

    • Author(s)
      Yoshiyasu Fukuyama
    • Publisher
      ELSEVIER
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] Studies in Natural Products Chemistry vol.3. "Seco-Prezizaane- and Anislactone-type Sesquiterpenes from Illicium species." (edited by Attarr Rhamann)2005

    • Author(s)
      Y.Fukuyama et al.
    • Publisher
      Elsevier, Amsterdam
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] Studies in Natural Products Chemistry, Vol.322005

    • Author(s)
      Yoshiyasu Fukuyama
    • Publisher
      ELSEVIER
    • Related Report
      2005 Annual Research Report
  • [Book] Interational Congress Series 1260. The Senescence-Accelerated Mouse (SAM) : An Animal Model of Senescence. "Neuroprotective Effect of Magnolol in the Hippocampus of Senescence-accelerated Mice (SAMP1)." (edited by Y.Nomura, T.Takeda, Y.Okuma)2004

    • Author(s)
      Y.Fukuyama et al.
    • Publisher
      Elsevier, Amsterdam
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] Illicium, Pimpinella and Foeniculum. "Chemical Constituents of the genus Illicium." (edited by M.M.Miro)2004

    • Author(s)
      Y.Fukuyama et al.
    • Publisher
      CRC Press, New York
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] Illicium, Pimpinella and Foeniculum2004

    • Author(s)
      Yoshiyasu Fukuyama
    • Total Pages
      231
    • Publisher
      CRC Press, New York
    • Related Report
      2004 Annual Research Report
  • [Patent(Industrial Property Rights)] トリシクロイリシノンを含む痴呆症治療薬2005

    • Inventor(s)
      福山愛保, 寺島孜郎
    • Industrial Property Rights Holder
      相模中央研究所
    • Filing Date
      2005-11-10
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Patent(Industrial Property Rights)] トリシクロイリシノンを含む痴呆症治療薬2005

    • Inventor(s)
      福山 愛保, 寺島 孜郎
    • Industrial Property Rights Holder
      相模中央研究所
    • Filing Date
      2005-11-10
    • Related Report
      2005 Annual Research Report
  • [Patent(Industrial Property Rights)] 痴呆症治療薬2003

    • Inventor(s)
      福山 愛保
    • Industrial Property Rights Holder
      相模中央化学研究
    • Filing Date
      2003-11-10
    • Related Report
      2004 Annual Research Report

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi