Antitumor ligands from marine organisms

• Project Area: Chemical Biology using bioactive natural products as specific ligands: identification of molecular targets and regulation of bioactivity
• Project/Area Number: 23102007
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Science and Engineering
• Research Institution: The University of Tokyo
• Principal Investigator: Matsunaga Shigeki 東京大学, 農学生命科学研究科, 教授 (60183951)
• Co-Investigator(Kenkyū-buntansha): Takada Kentaro 東京大学, 大学院農学生命科学研究科, 助教 (90455353)
• Co-Investigator(Renkei-kenkyūsha): Yoshida Minoru 理化学研究所, 吉田化学遺伝学研究室, 主任研究員 (00182791) ; Nogi Yuichi 海洋研究開発機構, 海洋・極限環境生物圏領域, 技術研究主幹 (70399559)
• Project Period (FY): 2011-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥35,490,000 (Direct Cost: ¥27,300,000、Indirect Cost: ¥8,190,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000); Fiscal Year 2013: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000); Fiscal Year 2012: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000); Fiscal Year 2011: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
• Keywords: 抗腫瘍性 / 細胞毒性 / 酵素阻害 / 海洋生物 / 単離 / 構造決定 / カイメン / 3Y1細胞 / 抗がん性 / 細胞周期 / 海産無脊椎動物 / 海洋微生物 / 探索

Outline of Final Research Achievements

Deep-sea marine invertebrates and marine bacteria were chosen as the untapped sources for discovery studies. From these species together with shallow water marine invertebrates, we searched for antitumor small molecules. From the extract of each organism, cytotoxic and enzyme inhibitory activities were examined and the active constituents were isolated and subjected to structural studies. From the isolated compounds we studied structure-activity relationships.

Research Products

• [Journal Article] Nazumazoles A-C, Cyclic Pentapeptides Dimerized through a Disulfide Bond from the Marine Sponge Theonella swinhoei. (2015)
  • Author(s): Fukuhara, K.; Takada, K.; Okada, S.; Matsunaga, S.
  • Journal Title: Org. Lett. Volume: 17 Issue: 11 Pages: 2646-2648
  • DOI: 10.1021/acs.orglett.5b01020
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Two Cell Differentiation Inducing Pyridoacridines from a Marine Sponge Biemna sp. and Their Chemical Conversions (2015)
  • Author(s): Moran, D.A.P., Takada, K., Ise, Y., Bontemps, N., Rohan, D., Furihata, K., Okada, S. and Matsunaga, S.
  • Journal Title: Tetrahedron Volume: 71 Issue: 30 Pages: 5013-5018
  • DOI: 10.1016/j.tet.2015.05.070
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Cytotoxic linear acetylenes from a marine sponge Pleroma sp. (2015)
  • Author(s): Takahashi, E., Takada, K., Hashimoto, M., Itoh, Y., Ise, Y., Otsuka, S., Okada, S. and Matsunaga, S.
  • Journal Title: Tetrahedron Volume: 71 Issue: 51 Pages: 9564-9570
  • DOI: 10.1016/j.tet.2015.10.062
  • Peer Reviewed
• [Journal Article] Cytotoxic Glycosylated Fatty Acid Amides from a Stelletta sp. Marine Sponge (2015)
  • Author(s): V. Peddie, K. Takada, S. Okuda, Y. Ise, Y. Morii, N. Yamawaki, T. Takatani, O. Arakawa,⊥ S. Okada, and S. Matsunaga
  • Journal Title: Journal of Natural Products Volume: 78 Issue: 11 Pages: 2808-2813
  • DOI: 10.1021/acs.jnatprod.5b00795
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Lower Homologues of Ahpatinin, Aspartic Protease Inhibitors, from a Marine Streptomyces sp. (2014)
  • Author(s): Y. Sun, K. Takada, Y. Nogi, S. Okada, S. Matsunaga
  • Journal Title: J. Nat. Prod. Volume: 77 Issue: 7 Pages: 1749-1752
  • DOI: 10.1021/np500337m
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Structural reappraisal of corticatic acids, biologically active linear polyacetylenes, from a marine sponge of the genus Petrosia (2014)
  • Author(s): K. Takada, S. Okada, S. Matsunaga
  • Journal Title: Fish. Sci. Volume: 80 Issue: 5 Pages: 1057-1064
  • DOI: 10.1007/s12562-014-0776-0
  • NAID: 40020207530
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Surugamides, Cyclic Octapeptides with Four D-Amino Acid Residues, from a Marine Streptomyces sp.: LCMS-Aided Inspection of Partial Hydrolysates for the Distinction of D- and L-Amino Acid Residues in the Sequence (2013)
  • Author(s): Takada, K.; Ninomiya A.; Naruse, M.; Sun, Y.; Miyazaki, M.; Nogi, Y.; Okada, S. Matsunaga, S.
  • Journal Title: J. Org. Chem. Volume: 78 Issue: 13 Pages: 6746-6750
  • DOI: 10.1021/jo400708u
  • Peer Reviewed
• [Journal Article] Stimulators of adiponenesis from the marine sponge Xestospongia testudinaria (2013)
  • Author(s): Akiyama, T.; Takada, K.; Oikawa, T.; Matsuura, N.; Ise, Y.; Okada, S.; Matsunaga, S.
  • Journal Title: Tetrahedron Volume: 69 Issue: 32 Pages: 6560-6564
  • DOI: 10.1016/j.tet.2013.06.007
  • Peer Reviewed
• [Journal Article] On the Assignment of the Absolute Configuration at the Isolated Methyl Branch in Miyakosyne A, Cytotoxic Linear Acetylene, from the Deep-Sea Marine Sponge Petrosia sp. (2013)
  • Author(s): Hitora, Y.; Takada, K.; Matsunaga, S.
  • Journal Title: Tetrahedron Volume: 69 Issue: 52 Pages: 11070-11073
  • DOI: 10.1016/j.tet.2013.11.013
  • Peer Reviewed
• [Journal Article] Isolation of cilliatamide D from a marine sponge Stelletta sp. and a reinvestigation of the configuration of ciliatamide A (2013)
  • Author(s): Imae, Y
  • Journal Title: J. Nat. Prod. Volume: 76 Issue: 4 Pages: 755-758
  • DOI: 10.1021/np300878b
  • Peer Reviewed
• [Journal Article] Gliotoxin analogues from a marine-derived fungus, Penicillium sp., and their cytotoxic and histone methyltransferase inhibitory activities (2012)
  • Author(s): Sun, Y
  • Journal Title: J. Nat. Prod. Volume: 75 Issue: 1 Pages: 111-114
  • DOI: 10.1021/np200740e
  • Peer Reviewed
• [Journal Article] Isolation of spirastrellolides A and B from a marine sponge Epiplasis sp. and their cytotoxic activities (2012)
  • Author(s): Suzuki, M
  • Journal Title: J. Nat. Prod. Volume: 75 Issue: 6 Pages: 1192-1195
  • DOI: 10.1021/np2009576
  • Peer Reviewed
• [Journal Article] Gliotoxin Analogues from a Marine-Derived Fungus, Penicillium sp., and Their Cytotoxic and Histone Methyltransferase Inhibitory Activities (2012)
  • Author(s): Yi, et al
  • Journal Title: J.Nat.Prod Volume: 75 Pages: 111-114
  • Peer Reviewed
• [Presentation] Structure elucidation of sponge metabolites with anti-tumor associated activities (2014)
  • Author(s): Kentaro Takada, Yasufumi Imae, Emi Takanashi, and Shigeki Matsunaga
  • Organizer: 4th Juior International Conference on Cutting-Edge Organic Chemistry in Asia
  • Place of Presentation: Bangkok. Thailan
  • Year and Date: 2014-11-29
  • Invited
• [Presentation] 海洋生物由来の生物活性物質：探索・単離・構造決定 (2014)
  • Author(s): 松永茂樹
  • Organizer: 第49回天然物化学談話会
  • Place of Presentation: 倉敷市
  • Year and Date: 2014-07-04
  • Invited
• [Presentation] カイメンTheonella swinhoei由来の新規ペプチドの単離と構造決定 (2014)
  • Author(s): 福原和哉、松永茂樹、その他
  • Organizer: 平成２６年度日本水産学会春季大会
  • Place of Presentation: 北海道大学水産学部
• [Presentation] Streptomyces属放線菌が生産するsurugamide類の生合成と機能に関する研究 (2014)
  • Author(s): 二宮章洋、松永茂樹、その他
  • Organizer: 平成２６年度日本水産学会春季大会
  • Place of Presentation: 北海道大学水産学部
• [Presentation] Cell differentiation inducers isolated from a marine sponge (2014)
  • Author(s): Daniel Pedrazzoli、松永茂樹、その他
  • Organizer: 平成２６年度日本水産学会春季大会
  • Place of Presentation: 北海道大学水産学部
• [Presentation] カイメン由来細胞毒性アセチレン化合物miyakosyne Aの遠隔位不斉中心の絶対配置の決定 (2014)
  • Author(s): 人羅勇気、松永茂樹、その他
  • Organizer: 平成２６年度日本水産学会春季大会
  • Place of Presentation: 北海道大学水産学部
• [Presentation] 屋久新曽根産カイメンTheonella sp.由来の新規HDAC1阻害物質の単離と構造決定 (2014)
  • Author(s): 高田健太郎、松永茂樹、その他
  • Organizer: 平成２６年度日本水産学会春季大会
  • Place of Presentation: 北海道大学水産学部
• [Presentation] 屋久新曽根産カイメンTheonella sp.由来の新規HDAC1阻害物質の単離と構造決定 (2013)
  • Author(s): 今榮康文、松永茂樹、その他
  • Organizer: 第55回天然有機化合物討論会
  • Place of Presentation: 同志社大学寒梅館
• [Presentation] Marine natural products with anti-cancer related activities (2013)
  • Author(s): Shigeki Matsunaga, Kentaro Takada, Yuki Hitora, Akihiro Ninomiya, Yasufumi Imae, Yi Sun, Masato Naruse, Emi Takanashi
  • Organizer: XIV International Symposium on Marine Natural Products
  • Place of Presentation: La Toja, Spain
  • Invited
• [Presentation] Marine Natural Products with Anti-cancer Related Activities (2013)
  • Author(s): Shigeki Matsunaga,* Kentaro Takada, Yuki Hitora, Akihiro Ninomiya, Yasufumi Imae, Yi Sun, Masato Naruse, Emi Takanashi, Masashi Suzuki
  • Organizer: 13th Intgernational Conference on the Chemistry of Antibiotics and Other Bioactive Compounds
  • Place of Presentation: 山梨県南都留郡
  • Invited
• [Presentation] 遺伝子組換え酵母を用いた小臥蛇島産カイメンからの新規ステロイド配糖体の単離および構造決定 (2013)
  • Author(s): 鈴木真志
  • Organizer: 平成25年度日本水産学会春季大会
  • Place of Presentation: 東京海洋大学
• [Presentation] カイメンStelletta sp.由来のciliatamide Dの構造決定およびciliatamide Aの絶対配置の精査 (2013)
  • Author(s): 今榮康文
  • Organizer: 平成25年度日本水産学会春季大会
  • Place of Presentation: 東京海洋大学
• [Presentation] 未同定種カイメン由来の薬剤耐性がん細胞に対する生育阻害物質の構造 (2013)
  • Author(s): 高梨笑未
  • Organizer: 平成25年度日本水産学会春季大会
  • Place of Presentation: 東京海洋大学
• [Presentation] 海洋放線菌Streptomyces sp.由来の新規ペプチドの単離と構造決定 (2013)
  • Author(s): 二宮章洋
  • Organizer: 平成25年度日本水産学会春季大会
  • Place of Presentation: 東京海洋大学
• [Presentation] Biologically active metabolites from sponges and microbes (2012)
  • Author(s): Shigeki Matsunaga
  • Organizer: The 9th Asia-Pacific Marine Biotechnology Conference
  • Place of Presentation: 高知市文化プラザ
  • Invited
• [Presentation] Bioactive ligands from marine organisms (2012)
  • Author(s): Shigeki Matsunaga
  • Organizer: 2012 International Symposium on Natural Product and Drug Discovery and Pharmaceutical Education
  • Place of Presentation: Sunchon National University, Korea
  • Invited
• [Presentation] Bioactive ligands from marine organisms (2012)
  • Author(s): Shigeki Matsunaga
  • Organizer: The 1st International Symposium on Chemical Biology of Natural Products: Target ID and Regulation of Bioactivity
  • Place of Presentation: 京都センチュリーホテル
  • Invited
• [Presentation] Bioactive ligands from marine organisms (2012)
  • Author(s): Shigeki Matsunaga
  • Organizer: The 7th International conference on cutting-edge organic Chemistry in Asia
  • Place of Presentation: Nanyang Technological University
  • Invited