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Design, Synthesis, and Biological Evaluation of Macrosphelide- based Compounds for Development of New Anticancer Agents

Research Project

Project/Area Number 19590098
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Drug development chemistry
Research InstitutionUniversity of Toyama

Principal Investigator

MATSUYA Yuji  University of Toyama, 大学院・医学薬学研究部(薬学), 助教 (50255858)

Co-Investigator(Kenkyū-buntansha) 根本 英雄  富山大学, 大学院・医学薬学研究部(薬学), 教授 (60006351)
近藤 隆  富山大学, 大学院・医学薬学研究部(医学), 教授 (40143937)
Co-Investigator(Renkei-kenkyūsha) NEMOTO Hideo  富山大学, 大学院・医学薬学研究部, 教授 (60006351)
KONDO Takashi  富山大学, 大学院・医学薬学研究部, 教授 (40143937)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsアポトーシス / 腫瘍細胞 / 薬物設計 / 構造活性相関 / 合成化学 / 癌 / 生理活性 / 有機化学
Research Abstract

天然物マクロスフェライドを基盤とした新規抗癌性医薬品探索を目的として、マクロスフェライドの16員環基本骨格に、強力な抗腫瘍性天然物であるエポチロン類のチアゾール側鎖を組み込んだ人工ハイブリッド化合物を設計し、合成研究を行った。また、マクロライド骨格の一部を窒素原子で置換した、アザ-アナログの設計と合成も行った。その結果、天然のマクロスフェライドを大きく上回る抗癌活性を示す、新規人工設計クロスフェライド誘導体を見出すことに成功した。

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (27 results)

All 2009 2008 2007 Other

All Journal Article (9 results) (of which Peer Reviewed: 9 results) Presentation (15 results) Remarks (3 results)

  • [Journal Article] Mechanism of Apoptosis Induced by a Newly Synthesized Derivative of Macrosphelides with a Thiazole Side Chain2009

    • Author(s)
      Ahmed, K. ; Matsuya, Y. ; Nemoto, H. ; Zaidi, S. F. H. ; Sugiyama, T. ; Yoshihisa, Y. ; Shimizu, T. ; Kondo, T.
    • Journal Title

      Chem. Biol. Interact 177

      Pages: 218-226

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Total Synthesis of 2-Nor-macrosphelide A and B2009

    • Author(s)
      Matsuya, Y. ; Matsushita, T. ; Sakamoto, K. ; Nemoto, H.
    • Journal Title

      Heterocycles 77

      Pages: 483-492

    • NAID

      40016405889

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Total Synthesis of 2 -Nor-macrosphelide A and B.2009

    • Author(s)
      Matsuya, Y., Matsushita, T., Sakamoto, K., Nemoto, H.
    • Journal Title

      Heterocycles 77

      Pages: 483-492

    • NAID

      40016405889

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mechanism of Apoptosis Induced by a Newly Synthesized Derivative of Macrosphelides with a Thiazole Side Chain2009

    • Author(s)
      Ahmed, K., Matsuya, Y., Nemoto, H., Zaldi, S. F. H., Sugiyama, T., Yoshihisa, Y., Shimizu, T., Kondo, T.
    • Journal Title

      Chemico Biological Interactions 177

      Pages: 218-226

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rapid and Transient Intracellular Oxidative Stress Due to Novel Macrosphelides Trigger Apoptosis via Fas/caspase-8-dependent Pathway in Human Lymphoma U937 Cells2007

    • Author(s)
      Ahmed, K. ; Zhao, Q.-L. ; Matsuya, Y. ; Yu, D.-Y. ; Feril, L. B., Jr. ; Nemoto, H. ; Kondo, T.
    • Journal Title

      Chem. Biol. Interact 170

      Pages: 86-99

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Enhancement of Macrosphelide-induced Apoptosis by Mild Hyperthermia2007

    • Author(s)
      Ahmed, K. ; Zhao, Q.-L. ; Matsuya, Y. ; Yu, D.-Y. ; Salunga, T. L. ; Nemoto, H. ; Kondo, T.
    • Journal Title

      Int. J. Hyperthermia 23+

      Pages: 353-361

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Rapid and Transient Intracellular Oxidative Stress Due to Novel Macrosphelides Trigger Apoptosis via Fas/caspase-8-dependent Pathway in Human Lymphoma U937 Cells2007

    • Author(s)
      Ahmed, K.; Zhao, Q.-L.; Matsuya, Y.;Yu, D.-Y, ; Feril, L. B., Jr.; Nemoto, H.; Kondo, T.
    • Journal Title

      Chemico Biological Interactions 170

      Pages: 86-99

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enhancement of Macrosphelide-induced Apoptosis by Mild Hyperthermia2007

    • Author(s)
      Ahmed, K.;Zhao, Q.-L.;Matsuya, Y.;Yu, D.-Y, ;Salunga, T. L;Nemoto, H.;Kondo, T.
    • Journal Title

      International Journal of Hyperthermia 23

      Pages: 353-361

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Design, Synthesis, and Biological Evaluation of Artificial Macrosphelides in Search for New Apoptosis-inducing Agents

    • Author(s)
      Matsuya, Y. ; Kobayashi, Y. ; Kawaguchi, T. ; Hori, A. ; Watanabe, Y. ; Ishihara, K. ; Ahmed, K. ; Wei, Z.-L. ; Yu, D. Y. ; Zhao, Q.-L.; Kondo, T. ; Nemoto, H.
    • Journal Title

      Chem. Eur. J. (in press)

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Presentation] 複素環含有マクロスフェライドの合成とアポトーシス誘導活性2008

    • Author(s)
      堀綾奈, 松谷裕二, Ahmed K., Zhao Q.-L., 近藤隆, 根本英雄
    • Organizer
      日本薬学会北陸支部第118回例会
    • Place of Presentation
      富山
    • Year and Date
      2008-07-05
    • Related Report
      2008 Final Research Report
  • [Presentation] Macrosphelide-Epothiloneハイブリッド化を基盤とした分子設計と創薬2008

    • Author(s)
      堀綾奈, 渡邊優香, 河村知美, 松谷裕二, , Ahmed K., Zhao Q.-L., 近藤隆, 根本英雄
    • Organizer
      創薬懇話会2008
    • Place of Presentation
      徳島
    • Related Report
      2008 Final Research Report
  • [Presentation] アポトーシス誘導による新規抗癌剤開発を指向したアザマクロスフェライド類の合成2008

    • Author(s)
      小林勇太, 堀綾奈, 松谷裕二, Ahmed K., Zhao Q.-L., 近藤隆, 根本英雄
    • Organizer
      創薬懇話会2008
    • Place of Presentation
      徳島
    • Related Report
      2008 Final Research Report
  • [Presentation] 複素環側鎖を導入した人工型macrosphelide類の設計と合成2008

    • Author(s)
      渡邊優香, 河村知美, 堀綾奈, 松谷裕二, Ahmed K., Zhao Q.-L., 近藤隆, 根本英雄
    • Organizer
      第38回複素環化学討論会
    • Place of Presentation
      福山
    • Related Report
      2008 Final Research Report
  • [Presentation] Aza-macrosphelide類の合成とアポトーシス誘導活性2008

    • Author(s)
      小林勇太, 堀綾奈, 松谷裕二, Ahmed K., Zhao Q.-L., 近藤隆, 根本英雄
    • Organizer
      第38回複素環化学討論会
    • Place of Presentation
      福山
    • Related Report
      2008 Final Research Report
  • [Presentation] Synthesis of Novel Artificial Macrosphelides as a New Apoptosis Inducing Agent2008

    • Author(s)
      Matsuya Y., Kobayash Y., Ishihara K., Kawaguchi T., Ahmed K., Zhao Q.-L., Kondo T., and Nemoto H
    • Organizer
      The 20^<th> French-Japanese Symposium on Medicinal and Fine Chemistry
    • Place of Presentation
      Bordeaux, France
    • Related Report
      2008 Final Research Report
  • [Presentation] Search for a New Anti-Cancer Agent by Design, Synthesis, and Biological Evaluation of Macrosphelide-Based Non-Natural Compounds2008

    • Author(s)
      Matsuya Y., Kobayash Y., Ishihara K., Kawaguchi T., Ahmed K., Zhao Q.-L., Kondo T., and Nemoto H
    • Organizer
      XXth International Symposium on Medicinal Chemistry
    • Place of Presentation
      Vienna, Austria
    • Related Report
      2008 Final Research Report
  • [Presentation] 新規マクロスフェライド誘導体によるアポトーシス誘導とその分子機構2008

    • Author(s)
      近藤隆, エヘメドカンワル, 松谷裕二, 趙慶利, 根本英雄
    • Organizer
      第17回日本アポトーシス研究会学術集会
    • Place of Presentation
      京都
    • Related Report
      2008 Final Research Report
  • [Presentation] Design and Synthesis of Macrosphelide Aza-analogues2008

    • Author(s)
      Kobayashi Y., Matsuya Y., and Nemoto H
    • Organizer
      The First International Symposium on Process Chemistry
    • Place of Presentation
      Kyoto
    • Related Report
      2008 Final Research Report
  • [Presentation] Synthesis and Bioactivity of Macrosphelide-based Artificial Compounds2008

    • Author(s)
      Matsuya Y., Kawaguchi T., Ahmed K., Zhao Q.-L., Kondo T., and Nemoto H.
    • Organizer
      The First International Symposium on Process Chemistry
    • Place of Presentation
      Kyoto
    • Related Report
      2008 Final Research Report
  • [Presentation] Hyperthermia-induced apoptosis and its enhancement by novel chemical compounds2008

    • Author(s)
      Kondo T., Yu D.Y., Matsuya Y., Zhao Q.L., Ahmed K., Wei Z.L., Hori T., and Nemoto H.
    • Organizer
      10th International Congress on Hyperthermic Oncology
    • Place of Presentation
      Munich, Germany
    • Related Report
      2008 Final Research Report
  • [Presentation] マクロスフェライド類を基盤としたドラッグデザインと合成2008

    • Author(s)
      堀綾奈, 松谷裕二, 根本英雄
    • Organizer
      日本薬学会第128年会
    • Place of Presentation
      横浜
    • Related Report
      2008 Final Research Report
  • [Presentation] アザマクロスフェライド類の合成研究2008

    • Author(s)
      小林勇太, 松谷裕二, 根本英雄
    • Organizer
      日本薬学会第128年会
    • Place of Presentation
      横浜
    • Related Report
      2008 Final Research Report
  • [Presentation] Search for a New Anti -Cancer Agent by Design, Synthesis, and Biological Evaluation of Macrosphelide -BasedNon-Natural Compounds.2008

    • Author(s)
      Matsuya Y., Kobayash Y., Ishihara K., Kawaguchi T., Ahmed K., Zhao Q. -L., Kondo T., Nemoto H.
    • Organizer
      XXth International Symposium on Medicinal Chemistry
    • Place of Presentation
      Vienna, Austria
    • Related Report
      2008 Annual Research Report
  • [Presentation] 含窒素型マクロスフェライド類縁体の設計と合成2007

    • Author(s)
      小林 勇太、松谷 裕二、根本 英雄
    • Organizer
      創薬懇話会
    • Place of Presentation
      富山観光ホテル
    • Year and Date
      2007-12-19
    • Related Report
      2007 Annual Research Report
  • [Remarks] 近藤隆, 松谷裕二, Yu D.-Y., Ahmed K., Zhao Q.-L., Wei Z.-L., 根本英雄 : 分子設計によるアポトーシスを標的とした増感剤の開発。第38回放射線による制癌シンポジウム-基礎と臨床の対話-. 第47回日本医学放射線学会生物部会学術大会2008, 6, 20-21, 高知.(招待講演)

    • Related Report
      2008 Final Research Report
  • [Remarks] 近藤隆, 松谷裕二, Yu D.-Y., Ahmed K., Zhao Q.-L., Wei Z.-L., 根本英雄 : 協会賞受賞講演、アポトーシスを標的とした新規合成増感剤の開発とその分子機構の解明. 第14回がん治療増感研究会2008, 6, 7-8, 鈴鹿(受賞講演)

    • Related Report
      2008 Final Research Report
  • [Remarks] 松谷裕二 : 「有機合成化学を基盤とする創薬研究」-新規合成薬によるアポトーシス誘導と酸化ストレス. フォーラム富山「創薬」, 2008, 5, 27, 富山. (招待講演)

    • Related Report
      2008 Final Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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