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Exploring new drug targets based on binding protein identification of bioactive natural products

Research Project

Project/Area Number 15H03114
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biomolecular chemistry
Research InstitutionOsaka University

Principal Investigator

ARAI Masayoshi  大阪大学, 薬学研究科, 特任教授(常勤) (80311231)

Co-Investigator(Renkei-kenkyūsha) KOBAYASHI Motomasa  大阪大学, 大学院・薬学研究科, 招へい教授 (40116033)
KOTOKU Naoyuki  立命館大学, 薬学部, 准教授 (20362618)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2017: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2016: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2015: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Keywords活性天然物 / 標的分子 / ケミカルバイオロジー / 感染症 / がん / 癌
Outline of Final Research Achievements

In this study, we conducted an exploratory study of bioactive natural products effective for cancer and tuberculosis using established screening systems focusing on unique phenotypic changes of cells and pathogenic microbes in tumor and infected region. As a result, 14 bioactive natural products containing 7 novel compounds were discovered. In addition, we analyzed the action mechanism and binding protein of isolated bioactive natural products using the methods of molecular biology or chemical biology. Then, several molecules that were expected to be new drug targets, were successfully identified.

Report

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

    (41 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research (4 results) Journal Article (12 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 12 results,  Acknowledgement Compliant: 7 results,  Open Access: 3 results) Presentation (22 results) (of which Int'l Joint Research: 8 results,  Invited: 7 results) Book (1 results) Remarks (2 results)

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

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] ランプン大学(インドネシア)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] University of KwaZulu Natal(南アフリカ)

    • Related Report
      2015 Annual Research Report
  • [Int'l Joint Research] Lampung University(インドネシア)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Discovery of a new diol-containing polyketide by heterologous expression of a silent biosynthetic gene cluster from Streptomyces lavendulae FRI-5.2018

    • Author(s)
      2.Pait, IGU., Kitani, S., Roslan, FW., Ulanova, D., Arai, M., Ikeda, H., Nihira, T.
    • Journal Title

      J. Ind. Microbio. Biotechnol.

      Volume: 45 Issue: 2 Pages: 77-87

    • DOI

      10.1007/s10295-017-1997-x

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Marine spongean polybrominated diphenyl ethers, selective growth inhibitors against the cancer cells adapted to glucose starvation, inhibits mitochondrial complex II2017

    • Author(s)
      Arai Masayoshi、Shin Dayoung、Kamiya Kentaro、Ishida Ryosuke、Setiawan Andi、Kotoku Naoyuki、Kobayashi Motomasa
    • Journal Title

      Journal of Natural Medicines

      Volume: 71 Issue: 1 Pages: 44-49

    • DOI

      10.1007/s11418-016-1025-x

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [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
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Anti-dormant mycobacterial activity of viomellein and xanthomegnin, naphthoquinone dimers produced by marine-derived Aspergillus sp.2017

    • Author(s)
      Kamiya K, Arai M, Setiawan A, Kobayashi M.
    • Journal Title

      Natural Product Communications.

      Volume: 12 Pages: 579-582

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Activation of cryptic phthoxazolin A production in Streptomyces avermitilis by the disruption of autoregulator-receptor homologue AvaR3.2017

    • Author(s)
      D.A. Suroto, S. Kitani, K.T. Miyamoto, Y. Sakihama, M. Arai, H. Ikeda, T. Nihira
    • Journal Title

      J. Biosci. Bioeng.

      Volume: 124 Issue: 6 Pages: 611-617

    • DOI

      10.1016/j.jbiosc.2017.06.014

    • NAID

      40021420041

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Exploring New Drug Targets through the Identification of Target Molecules of Bioactive Natural Products2016

    • Author(s)
      Masayoshi Arai
    • Journal Title

      YAKUGAKU ZASSHI

      Volume: 136 Issue: 4 Pages: 669-676

    • DOI

      10.1248/yakushi.15-00281

    • NAID

      130005140773

    • ISSN
      0031-6903, 1347-5231
    • Year and Date
      2016-04-01
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] <i>N</i>-Methylniphatyne A, a New 3-Alkylpyridine Alkaloid as an Inhibitor of the Cancer Cells Adapted to Nutrient Starvation, from an Indonesian Marine Sponge of <i>Xestospongia</i> sp.2016

    • Author(s)
      M. Arai, K. Kamiya, D. Shin, H. Matsumoto, T. Hisa, A. Setiawan, N. Kotoku, M. Kobayashi
    • Journal Title

      Chemical and Pharmaceutical Bulletin

      Volume: 64 Issue: 7 Pages: 766-771

    • DOI

      10.1248/cpb.c16-00118

    • NAID

      130005160059

    • ISSN
      0009-2363, 1347-5223
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Anti-dormant mycobacterial activity and target molecule of melophlins, tetramic acid derivatives isolated from a marine sponge of Melophlus sp.2016

    • Author(s)
      M. Arai, Y. Yamano, K. Kamiya, A. Setiawan, M. Kobayashi
    • Journal Title

      J. Nat. Med.

      Volume: 70 Issue: 3 Pages: 467-475

    • DOI

      10.1007/s11418-016-1005-1

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Search for Anti-angiogenic Substances from Natural Sources2016

    • Author(s)
      Kotoku, N.; Arai, M.; Kobayashi, M.
    • Journal Title

      Chemical and Pharmaceutical Bulletin

      Volume: 64 Issue: 2 Pages: 128-134

    • DOI

      10.1248/cpb.c15-00744

    • NAID

      130005121723

    • ISSN
      0009-2363, 1347-5223
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Enantioselective synthesis of dictyoceratin-A (smenospondiol) and -C, hypoxia-selective growth inhibitors from marine sponge2015

    • Author(s)
      Yuji Sumii, Naoyuki Kotoku, Akinori Fukuda, Takashi Kawachi, Yuta Sumii, Masayoshi Arai, Motomasa Kobayashi
    • Journal Title

      Bioorganic & Medicinal Chemistry

      Volume: 23 Issue: 5 Pages: 966-975

    • DOI

      10.1016/j.bmc.2015.01.021

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anti-dormant mycobacterial activity and target analysis of nybomycin produced by a marine-derived Streptomyces sp.2015

    • Author(s)
      Arai, M.; Kamiya, K.; Pruksakorn, P.; Sumii, Y.; Kotoku, N.; Joubert, J.-P.; Moodley, P.; Han, C.; Shin, D.; Kobayashi, M.
    • Journal Title

      Bioorg. Med. Chem.

      Volume: 23 Issue: 13 Pages: 3534-3541

    • DOI

      10.1016/j.bmc.2015.04.033

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Structure-activity relationship and in vivo anti-tumor evaluation of dictyoceratin-A and -C, hypoxia-selective growth inhibitors from marine sponge.2015

    • Author(s)
      Sumii, Y.; Kotoku, N.; Fukuda, A.; Kawachi, T.; Sumii, Y.; Arai, M.; Kobayashi, M.
    • Journal Title

      Marine Drugs

      Volume: 13 Issue: 12 Pages: 7419-7432

    • DOI

      10.3390/md13127074

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Exploring new medicinal seeds and drug targets from marine resources.2018

    • Author(s)
      Masayoshi Arai
    • Organizer
      JOINT SYMPOSIUM OF OSAKA UNIVERSITY WITH HIGHER EDUCATIONAL INSTITUTIONS OF BRUNEI DARUSSALAM
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [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] 海洋天然物の魅力と創薬研究への応用2017

    • Author(s)
      荒井雅吉
    • Organizer
      第40回 新適塾 「未来創薬への誘い」
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Structure-activity relationship and mechanistic analysis of biakamides, selective growth inhibitors against cancer cells under nutrient-starved conditions.2017

    • Author(s)
      ○Ryosuke Ishida, Naoyuki Kotoku, Hirokazu Matsumoto, Sayaka Ichii, Motomasa Kobayashi, Masayoshi Arai
    • Organizer
      The 10th Seoul-Kyoto-Osaka Joint Symposium
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Effect of new marine spongian diterpenes, ceylonamides G-I, on cancer cell spheroid.2017

    • Author(s)
      ○Takahiro Jomori, Andi Setiawan, Motomasa Kobayashi, Masayoshi Arai
    • Organizer
      The 10th Seoul-Kyoto-Osaka Joint Symposium
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 海洋由来微生物が産生する栄養飢餓環境適応がん細胞増殖阻害物質の探索2017

    • Author(s)
      ○石田 良典、唐 睿、木村 出海、小林 資正、荒井 雅吉
    • Organizer
      第67回日本薬学会近畿支部大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 抗潜在性結核物質 3-(phenethylamino)dimethyl(oxy)aaptamine の構造活性相関研究2017

    • Author(s)
      古徳直之、中村健彦、○野中宏起、山口亜由太、神谷謙太郎、小林資正、荒井雅吉
    • Organizer
      第67回日本薬学会近畿支部大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 海洋天然物を活用するケミカルバイオロジー研究2017

    • Author(s)
      荒井雅吉
    • Organizer
      第216回KMCセミナー
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Target Identification of Anti-mycobacterial Substance using Transformant Library of Mycobacteria2016

    • Author(s)
      Masayoshi Arai
    • Organizer
      The 8th Japan-Korea Chemical Biology Symposium
    • Place of Presentation
      パシフィックホテル沖縄(沖縄県那覇市)
    • Year and Date
      2016-01-18
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 海洋由来Trichoderma属真菌からの抗潜在性結核物質の探索2016

    • Author(s)
      荒井雅吉、○伊藤みなみ、神谷謙太朗、小林資正
    • Organizer
      日本生薬学会第64回年会
    • Related Report
      2016 Annual Research Report
  • [Presentation] 海洋天然物aaptamine類の潜在性結核菌に対する抗菌活性2016

    • Author(s)
      荒井雅吉,○神谷謙太朗, 韓 智秀, 山野 喜, 住井裕司, 中村健彦, 古徳直之, 小林資正
    • Organizer
      日本生薬学会第64回年会
    • Related Report
      2016 Annual Research Report
  • [Presentation] 低酸素環境選択的がん細胞増殖阻害物質dictyoceratin類の標的分子解析2016

    • Author(s)
      ○古徳直之,荒井雅吉,河内崇志,住井裕司,福田昭典,田中 駿,小林資正
    • Organizer
      第58回天然有機化合物討論会
    • Related Report
      2016 Annual Research Report
  • [Presentation] 海洋天然物で切拓く新規薬剤標的分子2016

    • Author(s)
      荒井雅吉
    • Organizer
      第21回 天然薬物の開発と応用シンポジウム
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] EXPLORING NEW DRUG TARGET BASED ON CHEMICAL BIOLOGY OF MARINE NATURAL PRODUCTS.2016

    • Author(s)
      Masayoshi Arai
    • Organizer
      8th US-JAPAN Symposium
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Phenotypic Screeningから見出す海洋天然物とその標的分子解析2016

    • Author(s)
      荒井雅吉
    • Organizer
      第15回化学系若手研究者セミナー
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Synthetic study and target analysis of dictyoceratin-A and -C, hypoxia-selective growth inhibitors from marine sponge.2015

    • Author(s)
      Naoyuki Kotoku, Yuji Sumii, Takashi Kawachi, Akinori Fukuda, Masayoshi Arai and Motomasa Kobayashi
    • Organizer
      PACIFICHEM 2015
    • Place of Presentation
      ホノルル(米国)
    • Year and Date
      2015-12-15
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Target identification of agelasine D, a marine spongean diterpene alkaloid, as an antidormant mycobacterial substance.2015

    • Author(s)
      Masayoshi Arai, Yoshi Yamano, Andi Setiawan and Motomasa Kobayashi
    • Organizer
      PACIFICHEM 2015
    • Place of Presentation
      ホノルル(米国)
    • Year and Date
      2015-12-15
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Anti-dormant mycobacterial activity and action-mechanism of nybomycin produced by Streptomyces sp.2015

    • Author(s)
      Kentaro Kamiya, Masayoshi Arai, Patamaporn Pruksakorn, Yuji Sumii, Naoyuki Kotoku, Chisu Han, Dayoung Shin and Motomasa Kobayashi
    • Organizer
      The 9th Seoul-Kyoto-Osaka Joint Symposium on Pharmaceutical Sciences for Young Scientists
    • Place of Presentation
      ソウル(韓国)
    • Year and Date
      2015-11-17
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [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(岐阜県岐阜市)
    • Year and Date
      2015-09-11
    • Related Report
      2015 Annual Research Report
  • [Presentation] 海綿由来環状デプシペプチドarenastatin Aの新規結合タンパク質の同定2015

    • Author(s)
      ○荒井雅吉,河内崇志,高市伸宏,馬田哲也,古徳直之,小林資正
    • Organizer
      第57回天然有機化合物討論会
    • Place of Presentation
      神奈川県民ホール(神奈川県横浜市)
    • Year and Date
      2015-09-09
    • Related Report
      2015 Annual Research Report
  • [Presentation] 低酸素環境選択的がん細胞増殖阻害物質dictyoceratin-Cの標的分子解析2015

    • Author(s)
      ○河内崇志,荒井雅吉,古徳直之,小林資正
    • Organizer
      第19回日本がん分子標的治療学会学術集会
    • Place of Presentation
      松山全日空ホテル(愛媛県松山市)
    • Year and Date
      2015-06-10
    • Related Report
      2015 Annual Research 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(大阪府富田林市)
    • Related Report
      2015 Annual Research Report
  • [Book] アルカロイドの科学2017

    • Author(s)
      荒井雅吉, 小林資正
    • Total Pages
      534
    • Publisher
      化学同人
    • ISBN
      9784759814187
    • Related Report
      2017 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
      2017 Annual Research 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 Annual Research Report

URL: 

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

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