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Molecular design of anti-metastatic sugars from lipophilic anti-invasive sugar derivatives

Research Project

Project/Area Number 09556022
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section展開研究
Research Field Bioproduction chemistry/Bioorganic chemistry
Research InstitutionMie University

Principal Investigator

KASHIMURA Naoki  Mie University, Faculty of Bioresources, Professor, 生物資源学部, 教授 (20026412)

Co-Investigator(Kenkyū-buntansha) SAIKI Ikuo  Toyama Medical and Pharmaceutical University, Institute of Oriental Medicine, Professor, 和漢薬研究所, 教授 (80133776)
INAGAKI Minoru  Mie University, Faculty of Bioresources, Assistant Professor, 生物資源学部, 助手 (20242935)
YOSHIDA Toshimichi  Mie University, Faculty of Medicine, Professor, 医学部, 教授 (80166959)
TANIMOTO Toshiko  Mukogawa Wemen's University, Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (10151870)
KIOKA Noriyuki  Kyoto University, Faculty of Agriculture, Assistant Professor, 農学部, 助手 (90234179)
坂倉 照〓 (坂倉 照よ)  三重大学, 医学部, 教授 (80073120)
Project Period (FY) 1997 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥11,600,000 (Direct Cost: ¥11,600,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1998: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1997: ¥5,600,000 (Direct Cost: ¥5,600,000)
Keywordslipophilic sugars / antimetstatic activities / human cancer cell lines / antiadhesive action / partially benzylated sugars / purine derivatives / 細胞接着阻害 / がん転移阻害 / 抗炎症活性 / 部分置換糖質 / ヒトがん細胞 / マウス乳がん細胞 / 脂溶性糖質誘導体 / がん転移自然モデル / がん転移血行モデル / 細胞毒性 / トリチルヌクレオシド / トリチルシクロデキストリン / がん転移 / 血管内皮細胞 / 接着分子 / がん細胞浸潤 / トリチル化糖
Research Abstract

This project aimed to focus on the anti-metastatic action of lipophilic sugar derivatives, to make molecular design, and to find out novel lead compounds for new anti-cancer drugs, based on the previous studies on the anti-adhesive sugar derivatives. Of 500 compounds investigated, 8 derivatives were finally selected to subject to a series of in vitro and in vivo tests. Partially benzylated sugars were found to be one of the best compounds for the cadidate of new lead compounds, because of their easy availability of both various isomers and materials, nontoxicity, and effective action in in vivo tests. Especially those available from biomass such as chitin, fucoidan, and xylan, are of interest for future development. Various purine derivatives were studied on their anti-tumor activities. Several ethynylpurine derivatives were found to exhibit specific inhibitory action against the expression of adhesion molecules of human endothelial cells. It was further found that 4 compounds exhibit strong anti-growth action against more than 30 human cancer cell lines with at the concentration of less than 10^<-6>M.One of them was found to be effective in vivo.The main features of the present study include expected new mechanism, low toxicity and availability from biomass at low cost.

Report

(5 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (38 results)

All Other

All Publications (38 results)

  • [Publications] 柏村直樹: "糖およびヌクレオシド誘導体のスクリーニング成績"癌と化学療法. 25. 266-266 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 柏村直樹: "糖およびプリン誘導体のスクリーニング成績"癌と化学療法. 27. 78-78 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 柏村直樹: "三重県バイオマスから抗癌活性を有する新規な部分ベンジル化糖と単離する試み"三重県における新規な生物資源高等利用法. 8-15 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 柏村直樹: "脂溶性糖質誘導体のがん転移阻害活性と生体膜への影響"三重県における生物資源の新規な高度利用. 7-12 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 柏村直樹: "脂溶性糖質誘導体の白血球および血管内皮細胞の影響"脂溶性糖質の動植物に対する挙動の調査. 18-22 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 柏村直樹: "糖質を素材とした新規な作用機構を有する脂溶性制がん剤の開発"生物資源を活用する新規な制がん剤の研究. 11-17 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] N.Kashimura: "The results of anti-cancer screening tests"Japanese J.Cancer Chemotherapy. 25. 266 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] N.Kashimura: "The results of anti-cancer screening tests"Japanese J.Cancer Chemotherapy. 27. 78 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] N.Kashimura: "Studies on the isolation and preparation of anti-inflammatory partially bencylated mono-and oligosacchafides frombiomass"Reports on the Study and Survey on the advanced application of novel bioresources in Mie Prefecture. 8-15 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] N.Kashimura: "Studies on the antimetastatic action and effect on biomembrane of lipophilic sugars"Report on the Study and Survey on the Advanced Application of Bioresources and Functional Molecules in Mie Prefecture. 7-12 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] N.Kashimura: "Studies on novel lipophilic sugar-based anticancer drugs with new mode of action"Report on the Study and Survey of novel bioresources-based anti-cancer drugs and endocrine disruptors in Mie Prefecture. 18-22 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] N.Kashimura: "Studies on novel lipophilic anti-cancer sugars derived from bioresources, and survey on endocrine disrupters in Mie Prefecture"Research Report, Mie Cooperative Research Center. 11-17 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 柏村直樹 他: "生物資源を活用する新規な制がん剤の研究と三重県における内分泌撹乱物質のバイオレミデーションの調査"三重大学地域共同研究センター研究報告. No.8. 144-150 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Inagaki,M. et al.: "Recognition of receptor lipopolysaccharides by spike G protein of bacteriophage φX174."Biosci.Biotech.Biochem.,. 64(9). 1993-1997 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 柏村直樹 他: "フェニルエチニルプリンリボサイドのがん転移抑制作用"日本農芸化学会誌. 75(印刷中). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Inagaki,M. et al: "Characterization of the binding of spike H protein of bacteriophage with receptor LPS."J.Biochem.,. 127. 577-583 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Inagaki,M. et al.: "Evaluation of specific binding of H protein of φX174 with maltose-biding toward LPS."J.Biochem.Mol.Biol.Biophys.. 4. 59-64 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kashimura,N. et al.: "Role of Mie Univ.in the regional S&T promation : Prospect of environmental lssues.Biotechnology, and TLO"Proceedings of the Fifth Restpor. Ses.4. 1-16 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 柏村直樹(編集): "生物資源を活用する新規な制がん剤の研究と三重県における内分泌撹乱物質の調査"三重県高等教育機関連絡会議. 555 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 柏村直樹: "Evaluation of specific binding of H Protein of bacteriophage φ×174 fused with MBPTOLPS"J.Biochem.Mol.Biol.Biophys. 2・1. 59-64 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 柏村直樹: "Charactrization of the binding of spike H protein of bacteriophage φ×174 with LPS"J.Biochem.(Tokyo). (印刷中). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 柏村直樹: "Synthesis and cytokinin activity of fluorescant 7-phenylethynyl・・・・・・"J.Agric.Food.chem.. (印刷中). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 柏村直樹: "アルキニルプリン類の生理活性"癌と化学療法. 27(印刷中). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 柏村直樹: "生物資源を活用する新規な制がん剤の開発と三重県における内分泌撹乱物質の調査"三重県高等教育機関連絡会議. 300 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 柏村直樹,他: "三重県における新規な生物資源高度利用法に関する調査と探索" 三重大学地域共同研究センター研究報告. No.6. 105-116 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kashimura et al.: "Novel anti-inflammatory and ants-tumob activietes of Some Trityl" International GlycoBio Technology Symposium'98. L15 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kashimura et al.: "Novel anti-tumoboctivities in vitro and in vivo of some liphophilic sugars" Proced.of 17th International Cancer Congress,Riode Japyrc. 97-101 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kashimura,et al.: "Specific Interaction of fused H protein of baeteriophage OX174 with receptor lipopolysaccharides" Virus Research. 60(1). 95-99 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 柏村直樹,他: "脂溶性糖質誘導体の白血球および血管内皮細胞の接着分子系に及ぼす影響" 糖鎖の新しい生理活性(第2回)10年度研究費企画調査. 2. 1-6 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 柏村直樹,他: "脂溶性糖質誘導体の細胞接着阻害活性(第10報)in vivoがん転移阻害作用" 日本農芸化学会誌. 73. 292 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 柏村直樹,他: "三重県における新規な生物資源高度利用法に関する調査と探索" 三重県高等教育機関連絡会議, 224 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 柏村直樹、 他: "Depolymeriza Tion of HA by low molewar-weight Amadoni Products." Biosci.Biotech.Biochem.,. 61. 188-190 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 柏村直樹、 他: "TK化合物の動物細胞に対する作用と細胞毒性" 三重大学地域共同研究センター研究報告. 5(印刷中). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 柏村直樹: "わが国における制かん候補物質のスクリーニングの成績第7報" 癌と化学療法. 25(印刷中). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] S.Noma, N.Kashimura: "Novel antiadhesive properties of some liphophilic hexusides." Biochemical Pharmacology. (予定). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] N.Kashimura, et al.: "Novel antiniflammatory and anti-tumor activiy of trityl sugars." Glycoconjugate Journal. (予定). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 柏村直樹、他: "トリチル基を有する誘導体の構造活性相関とがん細胞に対する拠動" 日本農芸化学会誌. 72(印刷中). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 柏村直樹、他: "遺伝子の構造と機能" 駒野徹編 学会出版センター p97〜118, 307 (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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