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Creation of new drug targets based on marine natural products

Research Project

Project/Area Number 18H02096
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 37020:Chemistry and chemical methodology of biomolecules-related
Research InstitutionOsaka University

Principal Investigator

ARAI MASAYOSHI  大阪大学, 薬学研究科, 教授 (80311231)

Co-Investigator(Kenkyū-buntansha) 君嶋 敦  大阪大学, 薬学研究科, 特任助教(常勤) (20812134)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2020: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2019: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2018: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Keywords海洋天然物 / 標的分子 / 生物活性 / 創薬標的
Outline of Final Research Achievements

In recent years, novel drug targets for cancer and infectious diseases (tuberculosis and amoebiasis) have been difficult to discover. In this study, we conducted an exploratory study of bioactive marine natural products effective for cancer and infectious diseases using established screening systems focusing on unique phenotypic changes of cells and pathogenic microbes in tumor and infected region. As a result, 11 bioactive marine natural products including a new compound were discovered. In addition, target molecule analysis was performed for a total of seven compounds, and target molecules were successfully identified for four of them.

Academic Significance and Societal Importance of the Research Achievements

これまで新規創薬標的は、細胞、動物、病原体等を用いた生物学または分子生物学的な手法による病態解析から見出される場合がほとんどであった。本研究は、創薬標的の枯渇が問題となっている「がん」や「感染症」に対して、それらに有効な海洋天然物(活性天然物)の探索と取得を行い、その結合タンパク質の解析を通して新たな創薬標的の開拓を目指している。本手法はこれまでとは異なるアプローチによる研究であり、見出された結合タンパク質はこれまでとは異なる新規創薬標的となる可能性が高い。また、見出した活性天然物は、医薬シーズとしての応用展開が可能であることから創薬化学領域への波及効果も期待できる。

Report

(4 results)
  • 2021 Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (35 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (6 results) Journal Article (15 results) (of which Int'l Joint Research: 12 results,  Peer Reviewed: 15 results,  Open Access: 5 results) Presentation (12 results) (of which Int'l Joint Research: 2 results,  Invited: 4 results) Book (1 results) Remarks (1 results)

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

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Assiut University(エジプト)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Lampung University(インドネシア)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] VAST(ベトナム)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Minia University(エジプト)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] ランプン大学(インドネシア)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Mitochondrial Targeting in an Anti-Austerity Approach Involving Bioactive Metabolites Isolated from the Marine-Derived Fungus Aspergillus sp.2020

    • Author(s)
      Abdel-Naime Waleed A、Kimishima Atsushi、Setiawan Andi、Fahim John Refaat、Fouad Mostafa A.、Kamel Mohamed Salah、Arai Masayoshi
    • Journal Title

      Marine Drugs

      Volume: 18 Issue: 11 Pages: 555-555

    • DOI

      10.3390/md18110555

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Selective cytotoxicity of marine-derived fungal metabolite (3S,6S)-3,6-dibenzylpiperazine-2,5-dione against cancer cells adapted to nutrient starvation2020

    • Author(s)
      Tang Rui、Zhou Dongyi、Kimishima Atsushi、Setiawan Andi、Arai Masayoshi
    • Journal Title

      The Journal of Antibiotics

      Volume: 73 Issue: 12 Pages: 873-875

    • DOI

      10.1038/s41429-020-0340-3

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] 3-(Phenethylamino)demethyl(oxy)aaptamine as an anti-dormant mycobacterial substance: Isolation, evaluation and total synthesis2020

    • Author(s)
      Sumii Yuji、Kotoku Naoyuki、Han Chisu、Kamiya Kentaro、Setiawan Andi、Vilch?ze Catherine、Jacobs William R.、Arai Masayoshi
    • Journal Title

      Tetrahedron Letters

      Volume: 61 Issue: 22 Pages: 151924-151924

    • DOI

      10.1016/j.tetlet.2020.151924

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Cytotoxic Activity of Abietane-Type Diterpenes Isolated From <i>Taxodium distichum</i> Against Cancer Cells Adapted to Nutrient-Starved Conditions2020

    • Author(s)
      Zaher Ahmed M.、Lin Jianyu、Arai Masayoshi
    • Journal Title

      Natural Product Communications

      Volume: 15 Issue: 3 Pages: 1-6

    • DOI

      10.1177/1934578x20915298

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Direct visualization of an antidepressant analog using surface-enhanced Raman scattering in the brain2020

    • Author(s)
      Masato Tanuma, Atsushi Kasai, Kazuki Bando, Naoyuki Kotoku, Kazuo Harada, Masafumi Minoshima, Kosuke Higashino, Atsushi Kimishima, Masayoshi Arai, Yukio Ago, Kaoru Seiriki, Kazuya Kikuchi, Satoshi Kawata, Katsumasa Fujita, Hitoshi Hashimoto
    • Journal Title

      JCI Insight

      Volume: 5 Issue: 6

    • DOI

      10.1172/jci.insight.133348

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Secalonic acid D as a selective cytotoxic substance on the cancer cells adapted to nutrient starvation2020

    • Author(s)
      Tang Rui、Kimishima Atsushi、Setiawan Andi、Arai Masayoshi
    • Journal Title

      Journal of Natural Medicines

      Volume: 74 Issue: 2 Pages: 495-500

    • DOI

      10.1007/s11418-020-01390-0

    • NAID

      40022183716

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A stereoselective construction of a cis-1,2-oxazadecaline skeleton using a substrate-controlled intramolecular oxy-Michael addition of tyrosine-derived hydroxylamines2020

    • Author(s)
      Kimishima Atsushi、Saito Hayato、Yamaguchi Ayuta、Arai Masayoshi
    • Journal Title

      Tetrahedron Letters

      Volume: 61 Issue: 4 Pages: 151412-151412

    • DOI

      10.1016/j.tetlet.2019.151412

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structure–Activity Relationship of Biakamide, Selective Growth Inhibitors under Nutrient-Starved Condition from Marine Sponge2019

    • Author(s)
      Ryosuke Ishida, Hirokazu Matsumoto, Sayaka Ichii, Motomasa Kobayashi, Masayoshi Arai, Naoyuki Kotoku
    • Journal Title

      Chemical and Pharmaceutical Bulletin

      Volume: 67 Issue: 3 Pages: 210-223

    • DOI

      10.1248/cpb.c18-00587

    • NAID

      130007606467

    • ISSN
      0009-2363, 1347-5223
    • Year and Date
      2019-03-01
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis, molecular docking, antimicrobial evaluation, and DNA cleavage assay of new thiadiazole/oxadiazole ciprofloxacin derivatives2019

    • Author(s)
      Mohammed Hamada H. H.、Abbas Samar H.、Abdelhafez El-Shimaa M. N.、Berger James M.、Mitarai Satoshi、Arai Masayoshi、Abuo-Rahma Gamal El-Din A. A.
    • Journal Title

      Monatshefte fur Chemie - Chemical Monthly

      Volume: 150 Issue: 10 Pages: 1809-1824

    • DOI

      10.1007/s00706-019-02478-4

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Cytotoxicity of New Diterpene Alkaloids, Ceylonamides G-I, Isolated From Indonesian Marine Sponge of Spongia sp.2019

    • Author(s)
      Jomori Takahiro、Setiawan Andi、Sasaoka Miho、Arai Masayoshi
    • Journal Title

      Natural Product Communications

      Volume: 14 Issue: 6 Pages: 1-7

    • DOI

      10.1177/1934578x19857294

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of biosynthetic genes for the β-carboline alkaloid kitasetaline and production of the fluorinated derivatives by heterologous expression2019

    • Author(s)
      Ueda, S., Ikeda, H., Namba, T., Ikejiri, Y., Nishimoto, Y., Arai, M., Nihira, T., Kitani, S.,
    • Journal Title

      J. Ind. Microbiol. Biotechnol.

      Volume: - Issue: 5 Pages: 739-750

    • DOI

      10.1007/s10295-019-02151-z

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] STRUCTURAL ELUCIDATION OF GLYCOSIDES FROM THE SEEDS OF Entada phaseoloides GROWING IN THUA THIEN HUE2019

    • Author(s)
      Cuong Le Canh Viet、Lien Le Thi、Nhi Nguyen Phuc Khanh、Ha Tran Phuong、Anh Le Tuan、Arai Masayoshi
    • Journal Title

      Vietnam Journal of Science and Technology

      Volume: 57 Issue: 2 Pages: 170-172

    • DOI

      10.15625/2525-2518/57/2/13098

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Design, synthesis and molecular docking of new N-4-piperazinyl ciprofloxacin-triazole hybrids with potential antimicrobial activity2019

    • Author(s)
      Mohammed Hamada H.H.、Abdelhafez El-Shimaa M.N.、Abbas Samar H.、Moustafa Gamal A.I.、Hauk Glenn、Berger James M.、Mitarai Satoshi、Arai Masayoshi、Abd El-Baky Rehab M.、Abuo-Rahma Gamal El-Din A.
    • Journal Title

      Bioorganic Chemistry

      Volume: 88 Pages: 102952-102952

    • DOI

      10.1016/j.bioorg.2019.102952

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] In vitro study on α-amylase and α-glucosidase inhibitory activities of a new stigmastane-type steroid saponin from the leaves of Vernonia amygdalina2019

    • Author(s)
      Anh Hoang Le Tuan、Vinh Le Ba、Lien Le Thi、Cuong Pham Viet、Arai Masayoshi、Ha Tran Phuong、Lin Hoang Ngoc、Dat Ton That Huu、Cuong Le Canh Viet、Kim Young Ho
    • Journal Title

      Natural Product Research

      Volume: 35 Issue: 5 Pages: 873-879

    • DOI

      10.1080/14786419.2019.1607853

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Target Identification of the Marine Natural Products Dictyoceratin-A and -C as Selective Growth Inhibitors in Cancer Cells Adapted to Hypoxic Environments2019

    • Author(s)
      Kawachi Takashi、Tanaka Shun、Fukuda Akinori、Sumii Yuji、Setiawan Andi、Kotoku Naoyuki、Kobayashi Motomasa、Arai Masayoshi
    • Journal Title

      Marine Drugs

      Volume: 17 Issue: 3 Pages: 163-163

    • DOI

      10.3390/md17030163

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 海洋薬用資源からのがんエクソソーム分泌阻害物質の探索2021

    • Author(s)
      ○林健宇, 三谷文美絵, 小根山千歳, 荒井雅吉
    • Organizer
      日本薬学会 第141年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Selective cytotoxicity of marine-derived fungal diketopiperazine against nutrient-starved cancer cells.2020

    • Author(s)
      Rui Tang, ○Dongyi Zhou, 君嶋 敦, Andi Setiawan, 荒井雅吉
    • Organizer
      第70回 日本薬学会関西支部大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 表現型スクリーニングによる天然物探索と標的分子解析2019

    • Author(s)
      荒井雅吉
    • Organizer
      第42回白金シンポジウム
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 腸内細菌叢との共棲関係に作用する新規赤痢アメーバ感染制御薬の探索2019

    • Author(s)
      吉田菜穂子、小林正規、荒井雅吉
    • Organizer
      第79回 日本寄生虫学会東日本支部大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Bioactive Compounds from Marine Resources and their Mode of Action2019

    • Author(s)
      荒井雅吉
    • Organizer
      THE 3rd JOINT SYMPOSIUM OF OSAKA UNIVERSITY WITH HIGHER EDUCATIONAL INSTITUTIONS OF BRUNEI DARUSSALAM
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Manzamine類の抗潜在性結核活性と標的分子解析2019

    • Author(s)
      木下遼祐、原 康雅、 君嶋 敦、 Andi Setiawan、荒井雅吉
    • Organizer
      日本生薬学会第66 回年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 表現型スクリーニングによるMONOTORI(ものとり)と標的分子解析2018

    • Author(s)
      荒井雅吉
    • Organizer
      第22回天然薬物の開発と応用シンポジウム
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Search for new medicinal seeds and drug targets from natural resources2018

    • Author(s)
      Masayoshi Arai
    • Organizer
      The 2nd Joint Symposium of Osaka University with Higher Educational Institutions of Brunei Darussalam
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 微生物共培養法を利用した活性天然物の探索2018

    • Author(s)
      城森啓宏, ◯原康雅, 笹岡美歩, Andi Setiawan, 荒井雅吉
    • Organizer
      第68回日本薬学会近畿支部大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 光親和性プローブを用いた抗潜在性結核物質PDOAの標的分子解析2018

    • Author(s)
      田中健太, ◯鍛治拓実, 神谷謙太朗, 古徳直之, 原 康雅, 小林資正, 荒井雅吉
    • Organizer
      第22回天然薬物の開発と応用シンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] 海洋真菌由来天然物DC1149B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機序解析2018

    • Author(s)
      ◯君嶋敦, 唐睿, 石田良典, 山口亞由太, 荒井雅吉
    • Organizer
      第60回天然有機化合物討論会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Arenastatin Aの標的タンパク質結合部位解析を指向したプローブ合成2018

    • Author(s)
      ◯加藤大貴, 神野佑司, 古徳直之, 君嶋 敦, 荒井雅吉
    • Organizer
      第68回日本薬学会近畿支部大会
    • Related Report
      2018 Annual Research Report
  • [Book] Cutting-Edge Organic Synthesis and Chemical Biology of Bioactive Molecules2019

    • Author(s)
      Yuichi Kobayashi (Ed), Masayoshi Arai
    • Total Pages
      355
    • Publisher
      Springer-Nature
    • Related Report
      2018 Annual Research Report
  • [Remarks] 大阪大学大学院 薬学研究科 天然物創薬学分野 ホームページ

    • URL

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

    • Related Report
      2018 Annual Research Report

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Published: 2018-04-23   Modified: 2023-01-30  

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