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植物内生真菌を用いたケミカルバイオロジーによる抗トキソプラズマ薬の探索

Research Project

Project/Area Number 20F20402
Research Category

Grant-in-Aid for JSPS Fellows

Allocation TypeSingle-year Grants
Section外国
Review Section Basic Section 38040:Bioorganic chemistry-related
Research InstitutionObihiro University of Agriculture and Veterinary Medicine

Principal Investigator

西川 義文  帯広畜産大学, 原虫病研究センター, 教授 (90431395)

Co-Investigator(Kenkyū-buntansha) ARIEFTA NANANG  帯広畜産大学, 原虫病研究センター, 外国人特別研究員
Project Period (FY) 2020-11-13 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2022: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 2021: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2020: ¥800,000 (Direct Cost: ¥800,000)
KeywordsEndophytes / Fungi / Ainu / Anti-Toxoplasma / Antimalaria / Cytotoxicity / 内生菌 / カビ / トキソプラズマ / マラリア / 細胞毒性
Outline of Research at the Start

本研究はインドネシア産および日本産植物の内生菌を利用し、インドネシアのヒト及び家畜動物で感染が蔓延しているトキソプラズマ原虫を含む原虫感染症を対象にした大規模な抗原虫活性のスクリーニングを実施する。有望な菌株については、産生化合物の同定を行い、作用機序の解明を進める。植物の内生菌から創薬シーズが発見されれば新たな生物資源価値を提供することができ、原虫病に対する創薬等への応用に必要な学問・技術分野の基盤の育成につながることが期待される。

Outline of Annual Research Achievements

The potent fungi from the screening processes will be applied to the isolation guided by anti-Toxoplasma and antimalaria activities (in vitro). These research steps are intended to confirm and trace the active agent(s) responsible for the anti-Toxoplasma and antimalaria activities. Firstly, each moldy media from scale-up fermentation (600 grams rice) will be extracted using methanol. The dried methanol extract will be suspended in distilled water and partitioned with hexane, chloroform, and ethyl acetate. Each fraction will be evaluated for anti-Toxoplasma activity and antimalaria. The active fraction(s) will be applied to various chromatography methods for further separations. Every step of column chromatography will be guided by anti-Toxoplasma and antimalarial activities, and only the active fractions will be further separated. LC-MS/MS profiling and molecular networking analyses for active fractions will be conducted to generate the compound's map, trace, and visualize the active components' cluster. The structures of isolated active compounds will be determined by spectroscopic methods, including nuclear magnetic resonance (NMR), high-resolution mass spectroscopy (HR-MS), and chemical derivatization. Anti-Toxoplasma and antimalaria effects on growth and cytotoxicity of isolated active compounds will also be evaluated in vitro. The efficacy of the most promising bioactive compounds will be evaluated using the mouse model. Furthermore, the potent fungi will be identified based on the ITS rDNA region.

Research Progress Status

令和4年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和4年度が最終年度であるため、記入しない。

Report

(3 results)
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (12 results)

All 2022 2021 Other

All Int'l Joint Research (3 results) Journal Article (4 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (3 results) Remarks (2 results)

  • [Int'l Joint Research] Mongolian Academy of Sciences(モンゴル)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] National University of Mongolia/Mongolian University of Life Sciences(モンゴル)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] Mulawarman University(インドネシア)

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Effect of α-Tocopheryloxy Acetic Acid on the Infection of Mice with Plasmodium berghei ANKA In Vivo and Humans with P. falciparum In Vitro.2022

    • Author(s)
      Ariefta NR, Kume A, Nishikawa Y, Taniguchi T, Umemiya-Shirafuji R, Kasai S, Suzuki H
    • Journal Title

      Acta Parasitol

      Volume: 67 Issue: 4 Pages: 1514-1520

    • DOI

      10.1007/s11686-022-00604-7

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sparsomycin Exhibits Potent Antiplasmodial Activity In Vitro and In Vivo2022

    • Author(s)
      Ariefta Nanang Rudianto、Pagmadulam Baldorj、Nihei Coh-ichi、Nishikawa Yoshifumi
    • Journal Title

      Pharmaceutics

      Volume: 14 Issue: 3 Pages: 544-544

    • DOI

      10.3390/pharmaceutics14030544

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Evaluation of Mongolian compound library for potential antimalarial and anti-Toxoplasma agents2021

    • Author(s)
      Banzragchgarav Orkhon、Ariefta Nanang R.、Murata Toshihiro、Myagmarsuren Punsantsogvoo、Battsetseg Badgar、Battur Banzragch、Batkhuu Javzan、Nishikawa Yoshifumi
    • Journal Title

      Parasitology International

      Volume: 85 Pages: 102424-102424

    • DOI

      10.1016/j.parint.2021.102424

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Spirocollequins A and B, new alkaloids featuring a spirocyclic isoindolinone core, from Colletotrichum boninense AM-12-22021

    • Author(s)
      Ariefta Nanang Rudianto、Koseki Takuya、Nishikawa Yoshifumi、Shiono Yoshihito
    • Journal Title

      Tetrahedron Letters

      Volume: 64 Pages: 152736-152736

    • DOI

      10.1016/j.tetlet.2020.152736

    • Related Report
      2021 Annual Research Report
  • [Presentation] アミノペプチダーゼ N 阻害剤フェベスチンは抗マラリア活性を有する2022

    • Author(s)
      Ariefta Nanang ,Pagmadulam Baldorj ,波多野 和樹 ,池田 のり子 ,一色 邦夫 ,五十嵐 雅之 ,二瓶 浩一 ,西川 義文
    • Organizer
      第91回日本寄生虫学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Ainu medicinal plants-associated fungi are potent sources of anti-Toxoplasma Agents2022

    • Author(s)
      Ariefta Nanang、網干 貴子、宮崎 直美、佐々木 祐士、西川 義文
    • Organizer
      第165回日本獣医学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Sparsomycin shows potent activity against malaria infection2021

    • Author(s)
      Nanang Ariefta、Baldorj Pagmadulam、二瓶 浩一、西川 義文
    • Organizer
      第164回日本獣医学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Remarks] 帯広畜産大学・原虫病研究センター・西川研究室

    • URL

      https://sites.google.com/site/nishihdlab/

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report 2020 Annual Research Report
  • [Remarks] 帯広畜産大学・原虫病研究センター

    • URL

      http://www.obihiro.ac.jp/~protozoa/index.html

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report 2020 Annual Research Report

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Published: 2020-11-16   Modified: 2024-03-26  

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