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Development of amphotericin B potenciators based on novel natural products

Research Project

Project/Area Number 18K06554
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 47010:Pharmaceutical chemistry and drug development sciences-related
Research InstitutionKitasato University

Principal Investigator

Ohtawa Masaki  北里大学, 薬学部, 准教授 (70453503)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords天然物合成化学 / 活性増強物質 / 天然物合成 / アムホテリシンB / 創薬化学 / 天然有機化合物 / 有機合成化学 / 活性増強剤
Outline of Final Research Achievements

The total synthesis of FKI-4981B, a new potentiator of amphotericin B activity against Candida albicans, was achieved. Our research results enabled the access of all stereoisomers of FKI-4981B and the elucidation of the unknown absolute configuration of FKI-4981B.Furthermore, one of the stereoisomers is a better amphotericin B potentiator than FKI-4981B and is an excellent lead compound for the development of a novel amphotericin B potentiator.

Academic Significance and Societal Importance of the Research Achievements

Amphotericin B (AMPB) は深在性真菌症に対する治療薬の第一選択であるものの、最大の欠点は副作用の重篤さである。そのため新たなAMPBの副作用軽減策の開発が急務である。北里大学薬学部において見出されたFKI-4981Bならびにshidoamideは天然由来のAMPB活性増強物質であり、これらをリード化合物する、これまでにないAMPBの副作用軽減する薬剤開発が望まれる。本研究成果にてそれを可能とする基盤を築くことができ、今後の研究により有望なAMPB活性増強物質が創出されることが期待される。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (9 results)

All 2021 2020 2019 2018

All Journal Article (4 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 4 results) Presentation (5 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] One-Pot γ-Lactonization of Homopropargyl Alcohols via Intramolecular Ketene Trapping2021

    • Author(s)
      Yamane Daichi、Tanaka Haruna、Hirata Akihiro、Tamura Yumiko、Takahashi Daichi、Takahashi Yusuke、Nagamitsu Tohru、Ohtawa Masaki
    • Journal Title

      Organic Letters

      Volume: 23 Issue: 7 Pages: 2831-2835

    • DOI

      10.1021/acs.orglett.1c00840

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Synthetic, Mechanistic, and Biological Interrogation of Ginkgo biloba Chemical Space En Route to (?)-Bilobalide2020

    • Author(s)
      Demoret Robert M.、Baker Meghan A.、Ohtawa Masaki、Chen Shuming、Lam Ching Ching、Khom Sophia、Roberto Marisa、Forli Stefano、Houk Kendall N.、Shenvi Ryan A.
    • Journal Title

      Journal of the American Chemical Society

      Volume: 142 Issue: 43 Pages: 18599-18618

    • DOI

      10.1021/jacs.0c08231

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Repair of DNA damage induced by the novel nucleoside analogue CNDAG through homologous recombination2020

    • Author(s)
      Liu Xiaojun、Jiang Yingjun、Nowak Billie、Ichikawa Satoshi、Ohtawa Masaki、Matsuda Akira、Plunkett William
    • Journal Title

      Cancer Chemotherapy and Pharmacology

      Volume: 85 Issue: 4 Pages: 661-672

    • DOI

      10.1007/s00280-020-04035-x

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Total Synthesis and Absolute Configuration of Simpotentin, a Potentiator of Amphotericin B Activity2019

    • Author(s)
      Ohtawa Masaki、Shimizu Eri、Saito Atsushi、Sakamoto Sayuri、Waki Ai、Kondo Ariko、Yagi Akiho、Uchida Ryuji、Tomoda Hiroshi、Nagamitsu Tohru
    • Journal Title

      Organic Letters

      Volume: 21 Issue: 14 Pages: 5596-5599

    • DOI

      10.1021/acs.orglett.9b01945

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] 構造の複雑な天然物の効率的な合成法の構築を目指して2021

    • Author(s)
      大多和正樹
    • Organizer
      日本薬学会第141年会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Amphotericin B活性増強作用を有するsimpotentinの全合成と絶対立体配置の決定2020

    • Author(s)
      大多和正樹、李大葵、内田龍児、供田洋、長光亨
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Research-status Report
  • [Presentation] Total synthesis and absolute configuration of simpotentin, a potentiator of amphotericin B activity2019

    • Author(s)
      Masaki Ohtawa, Ryuji Uchida, Hiroshi Tomoda, Tohru Nagamitsu
    • Organizer
      258th ACS National Meeting & Exposition
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Simpotentinの全合成と絶対立体配置の決定2018

    • Author(s)
      大多和 正樹、長光 亨
    • Organizer
      第41回白金シンポジウム
    • Related Report
      2018 Research-status Report
  • [Presentation] Amphotericin B活性増強作用を有するsimpotentinの全合成と絶対立体配置の決定2018

    • Author(s)
      大多和正樹、清水恵里、齋藤淳、李大葵、近藤あり子、 八木瑛穂、小林啓介、内田龍児、供田洋、長光亨
    • Organizer
      第44回反応と合成の進歩シンポジウム
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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