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Search for new anti-mycobacterial substances using established assay system focusing on the environments of infected region, and analysis of target molecule for development of new drug targets

Research Project

Project/Area Number 21310143
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Living organism molecular science
Research InstitutionOsaka University

Principal Investigator

ARAI Masayoshi  大阪大学, 大学院・薬学研究科, 准教授 (80311231)

Co-Investigator(Kenkyū-buntansha) KOBAYASHI Motomasa  大阪大学, 大学院・薬学研究科, 教授 (40116033)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2011: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2010: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2009: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Keywords感染症 / 結核 / 活性天然物 / ケミカルバイオロジー / 海綿 / 海洋微生物 / 抗生物質 / バイオテクノロジー
Research Abstract

To explore new medicinal leads for Tuberculosis, we succeeded in establishment of the screening systems focusing on the environments of Mycobacterium tuberculosis-infected region. Then, we searched the active substances from the extracts of marine organisms and the culture of marine microbe by established bioassay-guided separation. As a result, we isolated halicyclamins, trichoderins and nybomysin as anti-dormant mycobacterial substances. In addition, we succeeded in choosing the candidates of their target molecules by using genomic DNA library and/ or next-generation sequencer. On the other hand, desferrioxamine E was identified as an inhibitor of biofilm formation of Mycobacterium species. We also clarified the action-mechanism of desferrioxamine E as an inhibitor of biofilm formation.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (49 results)

All 2012 2011 2010 2009 Other

All Journal Article (18 results) (of which Peer Reviewed: 17 results) Presentation (27 results) Remarks (4 results)

  • [Journal Article] Action-mechanism of trichoderin A, an anti-dormant mycobacterial aminolipopeptide from marine sponge-derived Trichoderma sp.2011

    • Author(s)
      Pruksakorn P., Arai M., Liu L., Moodley P., Jacobs Jr. W. R., Kobayashi M.
    • Journal Title

      Biol. Pharm. Bull

      Volume: 34(8) Pages: 1287-1290

    • NAID

      130000936600

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] DedA protein relates to action-mechanism of halicyclamine A, a marine spongean macrocyclic alkaloid, as an anti-dormant mycobacterial substance2011

    • Author(s)
      Arai M., Liu L., Fujimoto T., Setiawan A., Kobayashi M.
    • Journal Title

      Marine Drugs

      Volume: 9(6) Pages: 984-993

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Inhibitory effect of cyclic trihydroxamate siderophore, desferrioxamine E, on the biofilm formation of Mycobacterium species2011

    • Author(s)
      Ishida S., Arai M., Nikawa H., Kobayashi M.
    • Journal Title

      Biol. Pharm. Bull

      Volume: 34(6) Pages: 917-920

    • NAID

      130000738072

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Action-Mechanism of Trichoderin A, an Anti-dormant Mycobacterial Aminolipopeptide from Marine Sponge-Derived Trichoderma sp.2011

    • Author(s)
      Patamapom Pruksakorn
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 34 Issue: 8 Pages: 1287-1290

    • DOI

      10.1248/bpb.34.1287

    • NAID

      130000936600

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibitory Effect of Cyclic Trihydroxamate Siderophore, Desferrioxamine E, on the Biofilm Formation of Mycobacterium Species2011

    • Author(s)
      Shunsuke Ishida
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 34 Issue: 6 Pages: 917-920

    • DOI

      10.1248/bpb.34.917

    • NAID

      130000738072

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anti-angiogenic effect of triterpenoidal saponins from Polygala senega.2011

    • Author(s)
      荒井雅吉、小林資正, ら
    • Journal Title

      J.Nat.Med.

      Volume: 65 Pages: 149-156

    • NAID

      10029460687

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Probe molecule equipped with boronic acid moiety as a reversible cross-linking group improves its binding affinity2010

    • Author(s)
      Kotoku N., Guo X. H., Arai M., Kobayashi M.
    • Journal Title

      Bioorg. Med. Chem. Lett

      Volume: 20(14) Pages: 4152-4155

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Trichoderins, novel aminolipopeptides from a marine sponge-derived Trichoderma sp., are active against dormant mycobacteria2010

    • Author(s)
      Pruksakorn P., Arai M., Kotoku N., Vilcheze C., Baughn A. D., Moodley P., Jacobs Jr. W. R., Kobayashi M.
    • Journal Title

      Bioorg. Med. Chem. Lett

      Volume: 20(12) Pages: 3658-3663

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] 海洋生物からの医薬シーズ探索2010

    • Author(s)
      荒井雅吉、小林資正
    • Journal Title

      有機合成化学協会誌

      Volume: 68巻 Pages: 470-479

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hypoxia-Selective Growth Inhibition of Cancer Cells by Furospinosulin-1, a Furanosesterterpene Isolated from an Indonesian Marine Sponge.2010

    • Author(s)
      荒井雅吉、小林資正, ら
    • Journal Title

      ChemMedChem

      Volume: 5 Pages: 1919-1926

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Probe molecule equipped with boronic acid moiety as a reversible cross-linking group improves its binding affinity.2010

    • Author(s)
      古徳直之、荒井雅吉、小林資正, ら
    • Journal Title

      Bioorg.Med.Chem.Lett.

      Volume: 20 Pages: 4152-4155

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Trichoderins, novel aminolipopeptides from a marine sponge-derived Trichoderma sp., are active against dormant mycobacteria2010

    • Author(s)
      Patamaporn PRUKSAKORN、荒井雅吉、小林資正, ら
    • Journal Title

      Bioorg.Med.Chem.Lett.

      Volume: 20 Pages: 3658-3663

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 海洋生物からの医薬シーズの探索2010

    • Author(s)
      荒井雅吉、小林資正
    • Journal Title

      有機合成化学協会誌

      Volume: 68 Pages: 470-479

    • NAID

      10026868871

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Haliclonacyclamines, tetracyclic alkylpiperidine alkaloids, as anti-dormant mycobacterial substances from a marine sponge of Haliclona sp2009

    • Author(s)
      Arai M., Ishida S., Setiawan A., Kobayashi M.
    • Journal Title

      Chem. Pharm. Bull

      Volume: 57(10) Pages: 1136-1138

    • NAID

      130000124793

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] 海洋天然物のケミカルバイオロジー2009

    • Author(s)
      荒井雅吉、小林資正
    • Journal Title

      化学と生物

      Volume: 47巻 Pages: 275-282

    • NAID

      10026435290

    • Related Report
      2011 Final Research Report 2009 Annual Research Report
  • [Journal Article] Pyripyropenes, fungal sesquiterpenes conjugated with α-pyrone and pyridine moieties, exhibits anti-angiogenic activity against human umbilical vein endothelial cells.2009

    • Author(s)
      Hayashi, A.; Arai, M.; Fujita, M.; Kobayashi, M.
    • Journal Title

      Biol.Pharm.Bull.

      Volume: 32 Pages: 1261-1265

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dysideamine, a new sesquiterpene aminoquinone, protects hippocampal neuronal cells against iodoacetic acid-induced cell death.2009

    • Author(s)
      Suna, H.; Arai, M.; Tsubotani, Y.; Hayashi, A.; Setiawan, A.; Kobayashi, M.
    • Journal Title

      Bioorg.Med.Chem.

      Volume: 17 Pages: 3968-3972

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Haliclonacyclamines, tetracyclic alkylpiperidine alkaloids, as anti-dormant mycobacterial substances from a marine sponge of Haliclona sp.2009

    • Author(s)
      Arai, M.; Ishida, S.; Setiawan, A.; Kobayashi, M.
    • Journal Title

      Chem.Pharm.Bull.

      Volume: 57 Pages: 1136-1138

    • NAID

      130000124793

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] 海綿由来の新しい医薬シーズの探索2012

    • Author(s)
      小林資正
    • Organizer
      中西シンポジウム2012
    • Place of Presentation
      慶応義塾大学日吉キャンパス(東京)(招待講演)
    • Year and Date
      2012-03-25
    • Related Report
      2011 Annual Research Report
  • [Presentation] 抗潜在性結核物質halicyclamine Aの作用メカニズム解析-ゲノムDNAライブラリーを利用する標的分子の解明-2011

    • Author(s)
      荒井雅吉、Liu Liu、藤本貴男、小林資正
    • Organizer
      第61回日本薬学会近畿支部総会・大会
    • Place of Presentation
      兵庫
    • Year and Date
      2011-10-22
    • Related Report
      2011 Final Research Report
  • [Presentation] 抗潜在性結核物質halicyclamine Aの作用メカニズム解析-ゲノムDNAライブラリーを利用する標的分子の解明-2011

    • Author(s)
      荒井雅吉
    • Organizer
      第61回日本薬学会近畿支部総会・大会
    • Place of Presentation
      神戸学院大学(兵庫)
    • Year and Date
      2011-10-22
    • Related Report
      2011 Annual Research Report
  • [Presentation] 海綿由来セスタテルペンheteroneminのbiofilm形成阻害活性2011

    • Author(s)
      韓智秀、荒井雅吉、石田俊介、新川大貴、小林資正
    • Organizer
      日本生薬学会第58回年会
    • Place of Presentation
      東京
    • Year and Date
      2011-09-24
    • Related Report
      2011 Final Research Report
  • [Presentation] インドネシア産海綿由来の新規環状デプシペプチドneamphamide Bの抗潜在性結核活性2011

    • Author(s)
      山野喜、荒井雅吉、小林資正
    • Organizer
      日本生薬学会第58回年会
    • Place of Presentation
      東京
    • Year and Date
      2011-09-24
    • Related Report
      2011 Final Research Report
  • [Presentation] インドネシア産海綿由来の新規環状デプシペプチドneamphamide Bの抗潜在性結核活性2011

    • Author(s)
      山野喜
    • Organizer
      日本生薬学会第58回年会
    • Place of Presentation
      昭和大学(東京)
    • Year and Date
      2011-09-24
    • Related Report
      2011 Annual Research Report
  • [Presentation] 海綿由来セスタテルペンheteroneminのbiofilm形成阻害活性2011

    • Author(s)
      韓智秀
    • Organizer
      日本生薬学会第58回年会
    • Place of Presentation
      昭和大学(東京)
    • Year and Date
      2011-09-24
    • Related Report
      2011 Annual Research Report
  • [Presentation] 海綿由来セスターテルペンheteroneminのbiofilm形成阻害活性2011

    • Author(s)
      石田俊介、荒井雅吉、小林資正, ら
    • Organizer
      日本薬学会第131年会
    • Place of Presentation
      静岡(グランシップ静岡)
    • Year and Date
      2011-03-29
    • Related Report
      2010 Annual Research Report
  • [Presentation] Andi Setiawan, Motomasa Kobayashi ANTI-MICROBIAL EFFECT OF MARINE SPONGEAN MACROCYCLIC ALKALOIDS, HALICYCLAMINES, AGAINST DORMANT MYCOBACTERIA ANDANALYSIS OF ITS ACTION MECHANISM2010

    • Author(s)
      Masayoshi Arai, Shunsuke Ishida, Liu Liu, Mari Soubou
    • Organizer
      The 13th International Symposium on Marine Natural Products
    • Place of Presentation
      Phuket(Thailand)
    • Year and Date
      2010-10-18
    • Related Report
      2011 Final Research Report
  • [Presentation] TRICHODERINS, NEW AMINOLIPOPEPTIDES FROM A MARINE SPONGE-DERIVED TRICHODERMA SP., ARE ACTIVE AGAINST DORMANT MYCOBACTERIA2010

    • Author(s)
      Masayoshi Arai, Patamaporn Pruksakorn, Yoshi Yamano, Motomasa Kobayashi
    • Organizer
      The 13th International Symposium on Marine Natural Products
    • Place of Presentation
      Phuket(Thailand)
    • Year and Date
      2010-10-18
    • Related Report
      2011 Final Research Report
  • [Presentation] ANTI-MICROBIAL EFFECT OF MARINE SPONGEAN MACROCYCLIC ALKALOIDS, HALICYCLAMINES, AGAINST DORMANT MYCOBACTERIA AND ANALYSIS OF ITS ACTION MECHANISM2010

    • Author(s)
      石田俊介、荒井雅吉、小林資正, ら
    • Organizer
      The 13th International Symposium on Marine Natural Products
    • Place of Presentation
      Hilton Phuket, Phuket (Thailand)
    • Year and Date
      2010-10-18
    • Related Report
      2010 Annual Research Report
  • [Presentation] TRICHODERINS, NEW AMINOLIPOPEPTIDES FROM A MARINE SPONGE-DERIVED TRICHODERMA SP, ARE ACTIVE AGAINST DORMANT MYCOBACTERIA2010

    • Author(s)
      山野喜、荒井雅吉、小林資正, ら
    • Organizer
      The 13th International Symposium on Marine Natural Products
    • Place of Presentation
      Hilton Phuket, Phuket(Thailand)
    • Year and Date
      2010-10-18
    • Related Report
      2010 Annual Research Report
  • [Presentation] 海洋由来放線菌が産生するdesferrioxamine Eのbiofilm形成阻害活性2010

    • Author(s)
      石田俊介、荒井雅吉、小林資正
    • Organizer
      日本生薬学会第57回年会
    • Place of Presentation
      徳島
    • Year and Date
      2010-09-25
    • Related Report
      2011 Final Research Report
  • [Presentation] 海洋由来放線菌が産生するdesferrioxamine Eのbiofilm形成阻害活性2010

    • Author(s)
      石田俊介、荒井雅吉、小林資正, ら
    • Organizer
      日本生薬学会学会第57回年会
    • Place of Presentation
      徳島(徳島文理大学)
    • Year and Date
      2010-09-25
    • Related Report
      2010 Annual Research Report
  • [Presentation] 海洋天然物由来の医薬シーズの探索2010

    • Author(s)
      小林資正
    • Organizer
      第27回和漢医薬学会学術大会
    • Place of Presentation
      京都
    • Year and Date
      2010-08-28
    • Related Report
      2011 Final Research Report
  • [Presentation] 海洋天然物由来の医薬シーズの探索2010

    • Author(s)
      小林資正
    • Organizer
      第27回和漢医薬学会学術大会
    • Place of Presentation
      京都(京都薬科大学)(招待講演)
    • Year and Date
      2010-08-28
    • Related Report
      2010 Annual Research Report
  • [Presentation] 海洋由来微生物からの抗潜在性結核物質の探索2010

    • Author(s)
      荒井雅吉、山野喜、Patamaporn PRUKSAKORN、Ahmed Mohamed MOHAMED、小林資正
    • Organizer
      日本薬学会第130年会
    • Place of Presentation
      岡山
    • Year and Date
      2010-03-29
    • Related Report
      2011 Final Research Report 2009 Annual Research Report
  • [Presentation] 海洋由来真菌が産生するsterigmatocystin類のbiofilm形成阻害活性2010

    • Author(s)
      荒井雅吉、石田俊介、小林資正
    • Organizer
      第83回日本細菌学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2010-03-29
    • Related Report
      2011 Final Research Report 2009 Annual Research Report
  • [Presentation] Cell-based assayを基盤とする天然薬物由来の医薬シーズの探索2010

    • Author(s)
      小林資正、古徳直之、荒井雅吉
    • Organizer
      日本薬学会第130年会
    • Place of Presentation
      岡山
    • Year and Date
      2010-03-29
    • Related Report
      2009 Annual Research Report
  • [Presentation] 海綿由来の大環状アルカロイドhalicyclamine類の潜在性結核菌に対する抗菌活性とその作用メカニズムの解析2009

    • Author(s)
      荒井雅吉、劉柳、石田俊介、惣坊真理、小林資正
    • Organizer
      第28回メディシナルケミストリーシンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2009-11-25
    • Related Report
      2011 Final Research Report 2009 Annual Research Report
  • [Presentation] 海洋由来真菌が産生する新規アミノリポペプチドtrichoderin類の抗結核活性2009

    • Author(s)
      Patamaporn Pruksakorn、荒井雅吉、古徳直之、小林資正
    • Organizer
      第59回日本薬学会近畿支部総会・大会
    • Place of Presentation
      大阪
    • Year and Date
      2009-10-24
    • Related Report
      2009 Annual Research Report
  • [Presentation] 海洋由来真菌が産生する5-methoxysterigmatocystinのbiofilm形成阻害活性2009

    • Author(s)
      石田俊介、荒井雅吉、坪谷好恵、小林資正
    • Organizer
      第59回日本薬学会近畿支部総会・大会
    • Place of Presentation
      大阪
    • Year and Date
      2009-10-24
    • Related Report
      2009 Annual Research Report
  • [Presentation] 海洋由来真菌が産生する新規アミノリポペプチドtrichoderin類の抗結核活性とその作用メカニズム2009

    • Author(s)
      荒井雅吉、Patamaporn Pruksakorn、古徳直之、小林資正
    • Organizer
      日本生薬学会第56回年会
    • Place of Presentation
      京都
    • Year and Date
      2009-10-04
    • Related Report
      2011 Final Research Report 2009 Annual Research Report
  • [Presentation] 海洋由来真菌が産生するsterigmatocystin類のbiofilm形成阻害活性2009

    • Author(s)
      荒井雅吉、石田俊介、坪谷好恵、小林資正
    • Organizer
      日本生薬学会第56回年会
    • Place of Presentation
      京都
    • Year and Date
      2009-10-04
    • Related Report
      2011 Final Research Report 2009 Annual Research Report
  • [Presentation] 海綿由来の大環状アルカロイドhaliclonacyclamine類の潜在性結核菌に対する抗菌活性とその作用メカニズム解析2009

    • Author(s)
      荒井雅吉、劉柳、石田俊介、藤本貴男、惣坊真理、小林資正
    • Organizer
      日本生薬学会第56回年会
    • Place of Presentation
      京都
    • Year and Date
      2009-10-04
    • Related Report
      2009 Annual Research Report
  • [Presentation] Search for Medicinal Seed from Marine Organisms2009

    • Author(s)
      Motomasa Kobayashi, Naoyuki Kotoku, Masayoshi Arai
    • Organizer
      The 25th Naito Conference on Chemical Biology[ II]
    • Place of Presentation
      北海道
    • Year and Date
      2009-09-10
    • Related Report
      2011 Final Research Report
  • [Presentation] Search for Medicinal Seed from Marine Organisms.2009

    • Author(s)
      Motomasa Kobayashi, Naoyuki Kotoku, Masayoshi Arai
    • Organizer
      The 25th Naito Conference on Chemical Biology [II]
    • Place of Presentation
      北海道
    • Year and Date
      2009-09-10
    • Related Report
      2009 Annual Research Report
  • [Remarks]

    • URL

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

    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

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

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

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

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

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

    • Related Report
      2009 Annual Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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