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Medicinal chemistry study of bioactive marine natural products targeting tumor microenvironment

Research Project

Project/Area Number 15K07996
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Natural medicines
Research InstitutionRitsumeikan University (2017)
Osaka University (2015-2016)

Principal Investigator

KOTOKU NAOYUKI  立命館大学, 薬学部, 准教授 (20362618)

Co-Investigator(Renkei-kenkyūsha) ARAI MASAYOSHI  大阪大学, 薬学研究科, 特任教授 (80311231)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords天然活性物質 / 海洋天然物 / 創薬化学 / 抗がん剤 / がん微小環境
Outline of Final Research Achievements

Medicinal chemistry study of bioactive marine natural products targeting tumor microenvironment were executed. As for biakamides, novel polyketides as selective growth inhibitors against cancer cells under glucose-deprived condition, total synthesis and structure-activity relationship study were accomplished. Then, mechanistic study of biakamides using photoaffinity probe revealed that biakamides inhibited the respiratory complex I in mitochondria.
We also analyzed the structure-activity relationship of furospinosulin-1, hypoxia-selective growth inhibitor against cancer cells, for developing potent anti-cancer drug leads, and revealed that structural modification at the end of side chain by PEG and some polar substituents were effective to improve cell permeability and growth inhibitory activity toward cancer cells.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (16 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research (2 results) Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Acknowledgement Compliant: 1 results) Presentation (12 results) (of which Int'l Joint Research: 1 results,  Invited: 4 results) Remarks (1 results)

  • [Int'l Joint Research] Lampung University(インドネシア)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] Lampung University(インドネシア)

    • Related Report
      2016 Research-status Report
  • [Journal Article] Biakamides A-D, Unique Polyketides from a Marine Sponge, Act as Selective Growth Inhibitors of Tumor Cells Adapted to Nutrient Starvation2017

    • Author(s)
      Naoyuki Kotoku, Ryosuke Ishida, Hirokazu Matsumoto, Masayoshi Arai, Kazunari Toda, Andi Setiawan, Osamu Muraoka, and Motomasa Kobayashi
    • Journal Title

      The Journal of Organic Chemistry

      Volume: 82 Issue: 3 Pages: 1705-1718

    • DOI

      10.1021/acs.joc.6b02948

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Synthesis and mechanistic Studies of Biakamides, Naturally-occurring Anti-austerity Agents Targeting Mitochondria2018

    • Author(s)
      Ryosuke Ishida, Hirokazu Matsumoto, Sayaka Ichii, Masayoshi Arai, Motomasa Kobayashi, Naoyuki Kotoku
    • Organizer
      4th International Symposium for Medicinal Sciences
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 海綿由来ブロモフェノール類のグルコース飢餓環境選択的増殖阻害活性と作用メカニズム解析2017

    • Author(s)
      古徳直之、申多英、石田良典、松本紘和、久智也、戸田和成、荒井雅吉、小林資正
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台国際センター
    • Year and Date
      2017-03-24
    • Related Report
      2016 Research-status Report
  • [Presentation] 新規海洋天然物biakamide類の栄養飢餓環境選択的がん細胞増殖阻害活性とその作用メカニズム2017

    • Author(s)
      石田 良典、古徳 直之、荒井 雅吉
    • Organizer
      第21回日本がん分子標的治療学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 栄養飢餓環境選択的がん細胞増殖阻害活性物質biakamide類の合成研究と作用機序解析2017

    • Author(s)
      石田良典、松本紘和、一井さやか、荒井雅吉、小林資正、古徳直之
    • Organizer
      第59回天然有機化合物討論会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 有機合成化学を基盤とする海洋天然物のケミカルバイオロジー研究2017

    • Author(s)
      古徳直之
    • Organizer
      第37回有機合成若手セミナー ~明日の有機合成を担う人のために~
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 栄養飢餓環境選択的がん細胞増殖阻害物質biakamide類の構造活性相関と作用メカニズム解析2016

    • Author(s)
      石田良典、古徳直之、松本紘和、荒井雅吉、小林資正
    • Organizer
      第21回天然薬物の開発と応用シンポジウム
    • Place of Presentation
      千葉大学薬学部120周年記念講堂
    • Year and Date
      2016-10-27
    • Related Report
      2016 Research-status Report
  • [Presentation] 海洋天然物を基軸とした創薬への挑戦2016

    • Author(s)
      古徳直之
    • Organizer
      第2回近畿薬学シンポジウム・化学系の若い力
    • Place of Presentation
      大阪大学薬学部沢井ホール
    • Year and Date
      2016-06-04
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 海洋生物由来の栄養飢餓選択的増殖阻害物質の探索と創薬への展開2016

    • Author(s)
      古徳直之
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-03-27
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] グルコース飢餓環境選択的がん細胞増殖阻害活性を有するポリケチドbiakamide類の全合成と構造活性相関2015

    • Author(s)
      ○石田良典,古徳直之,松本紘和,荒井雅吉,小林資正
    • Organizer
      第41回反応と合成の進歩シンポジウム
    • Place of Presentation
      近畿大学
    • Year and Date
      2015-10-26
    • Related Report
      2015 Research-status Report
  • [Presentation] グルコース飢餓環境選択的増殖阻害物質biakamide類の構造活性相関研究2015

    • Author(s)
      ○石田良典,古徳直之,松本紘和,田畑奎太朗,小林資正
    • Organizer
      第65回日本薬学会近畿支部総会・大会
    • Place of Presentation
      大阪大谷大学
    • Year and Date
      2015-10-17
    • Related Report
      2015 Research-status Report
  • [Presentation] 低栄養選択的増殖阻害物質fasciospyrinadinoneの全合成2015

    • Author(s)
      古徳直之,松本紘和,○久智也,戸田和成,荒井雅吉,小林資正
    • Organizer
      第65回日本薬学会近畿支部総会・大会
    • Place of Presentation
      大阪大谷大学
    • Year and Date
      2015-10-17
    • Related Report
      2015 Research-status Report
  • [Presentation] 栄養飢餓環境選択的がん細胞増殖阻害物質の探索2015

    • Author(s)
      荒井雅吉,○申多英,松本紘和,神谷謙太朗,久智也,古徳直之,小林資正
    • Organizer
      日本生薬学会第62年会
    • Place of Presentation
      長良川国際会議場
    • Year and Date
      2015-09-11
    • Related Report
      2015 Research-status Report
  • [Remarks] 大阪大学大学院薬学研究科天然物化学分野ホームページ

    • URL

      http://www.phs.osaka-u.ac.jp/homepage/b012/

    • Related Report
      2016 Research-status Report 2015 Research-status Report

URL: 

Published: 2015-04-16   Modified: 2019-03-29  

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