Design and synthesis of novel anticancer compound based on the molecular mode of action of the marine pyrrole alkaloid lamellarin

• Project/Area Number: 21580248
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Fisheries chemistry
• Research Institution: Nagasaki University
• Principal Investigator: ISHIBASHI Fumito 長崎大学, 大学院・水産・環境科学総合研究科, 教授 (10192486)
• Co-Investigator(Kenkyū-buntansha): OSATOMI Kiyoshi 長崎大学, 大学院水産・環境科学総合研究科, 教授 (40253702)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2009: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 天然物化学 / 生理活性物質 / トポイソメラーゼI阻害 / 海洋天然物 / 分子設計 / ピロールアルカロイド / ラメラリン / 海産天然物

Research Abstract

Based on the molecular mode of action of topoisomerase I inhibition of the marine anticancer alkaloid lamellarin, two novel lamellarin analogs named as isolamellarin and bislactone were designed as anticancer agents and synthesized. Isolamellarin was shown to have twice as high antiproliferative activity as the parent compound lamellarin D on HeLa cell line due to topoisomerase I inhibition.

Research Products

• [Journal Article] Algicidal Activity of Glycerolipids from the Brown Alga Ishige sinicola on Red Tide Microalgae (2012)
  • Author(s): Shotaro Hirao, Kenji Tara, Kazuyoshi Kuwano, Junji Tanaka, Fumito Ishibashi
  • Journal Title: Biosci. Biotechnol. Biochem Volume: 76巻 Pages: 372-374
  • Peer Reviewed
• [Journal Article] Algicidal Activity of Glycerolipids from Brown Alga Ishige sinicola toward Red Tide Microalgae (2012)
  • Author(s): Shotaro Hirao, Kenji Tara, Kazuyoshi Kuwano, Junji Tanaka, Fumito Ishibashi
  • Journal Title: Bioscience, Biotechnology, and Biochemistry Volume: 76 Issue: 2 Pages: 372-374
  • DOI: 10.1271/bbb.110645
  • NAID: 10030400197
  • ISSN: 0916-8451, 1347-6947
  • Peer Reviewed
• [Journal Article] Synthesis, structure-activity relationships, and mechanism of action of anti-HIV-1 lamellarin a 20-sulfate analogues (2011)
  • Author(s): Haruka Kamiyama, Yoshinao Kubo, Hironori Sato, Naoki Yamamoto, Tsutomu Fukuda, Fumito Ishibashi, Masatomo Iwao
  • Journal Title: Bioorg. Med. Chem Volume: 19巻 Pages: 7541-7550
  • Peer Reviewed
• [Journal Article] Synthesis and Biological Activity of Lamellarin Alkaloids : An Overview (2011)
  • Author(s): Tsutomu Fukuda, Fumito Ishibashi, Masatomo Iwao
  • Journal Title: Heterocycles Volume: 83巻 Pages: 491-529
  • NAID: 120006984843
  • Peer Reviewed
• [Journal Article] A Formal Total Synthesis of the Telomerase Inhibitor Dictyodendrin B (2010)
  • Author(s): Shotaro Hirao, Yuki Yoshinaga, Masatomo Iwao, Fumito Ishibashi
  • Journal Title: Tetrahedron Lett Volume: 51巻 Pages: 533-536
  • NAID: 120006984589
  • Peer Reviewed
• [Journal Article] A Formal Total Synthesis of the Telomerase Inhibitor Dictyodendrin B (2010)
  • Author(s): Shotaro Hirao, Yuki Yoshinaga, Masatomo Iwao, Fumito Ishibashi
  • Journal Title: Tetrahedron Letters 51 Pages: 533-536
  • NAID: 120006984589
  • Peer Reviewed
• [Journal Article] Synthetic Approach to Telomerase Inhibitor Dictyodendrin B : Synthesis of the Pyrrolo[ 2, 3-c] carbazole Core (2009)
  • Author(s): Shotaro Hirao, Yumiko Sugiyama, Masatomo Iwao, Fumito Ishibashi
  • Journal Title: Biosci. Biotechnol. Biochem Volume: 73巻 Pages: 1764-1772
  • NAID: 10027544373
  • Peer Reviewed
• [Journal Article] Design and Synthesis of Lamellarin D Analogues Targeting Topoisomerase I (2009)
  • Author(s): Takeshi Ohta, Tsutomu Fukuda, Fumito Ishibashi, Masatomo Iwao
  • Journal Title: J. Org. Chem Volume: 74巻 Pages: 8143-8153
  • Peer Reviewed
• [Journal Article] Design and Synthesis of Lamellarin D Analogues Targeting Topoisomerase I (2009)
  • Author(s): Takeshi Ohta, Tsutomu Fukuda, Fumito Ishibashi, Masatomo Iwao
  • Journal Title: Journal of Organic Chemistry 74 Pages: 8143-8153
  • Peer Reviewed
• [Journal Article] Synthetic Approach to Telomerase Inhibitor Dictyodendrin B : Synthesis of the Pyrrolo[2,3-c]carbazole Core (2009)
  • Author(s): Shotaro Hirao, Yumiko Sugiyama, Masatomo Iwao, Fumito Ishibashi
  • Journal Title: Bioscience, Biotechnology and Biochemistry 73 Pages: 1764-1772
  • NAID: 10027544373
  • Peer Reviewed
• [Presentation] 光学活性16-メチルラメラリンNの絶対配置の決定とプロテインキナーゼ阻害活性評価 (2012)
  • Author(s): 吉田賢佑、糸山諒介、福田勉、石橋郁人、岩尾正倫、Laurent Meijer
  • Organizer: 日本化学会第92春季年会
  • Place of Presentation: 横浜
• [Presentation] Total Synthesis of the Marine Pyrrolocarbazole Alkaloid Dictyodendrin B (2011)
  • Author(s): S.Hirao, Y.Yoshinaga, M.Iwao, F.Ishibashi
  • Organizer: 23^<rd> International Congress of Heterocyclic Chemistry
  • Place of Presentation: 英国、グラスゴー
  • Year and Date: 2011-08-02
• [Presentation] 海洋天然物ラメラリンをモデルとした新規トポイソメラーゼI阻害活性物質の創製 (2011)
  • Author(s): 福永光希、柱野彩、石橋郁人、岩尾正倫
  • Organizer: 日本農芸化学会西日本支部・中国四国支部合同大会
  • Place of Presentation: 宮崎
• [Presentation] Total Synthesis of the Marine Pyrrolocarbazole Alkaloid Dictyodendrin B (2011)
  • Author(s): S. Hirao, Y. Yoshinaga, M. Iwao, F. Ishibashi
  • Organizer: 23rd International Congress of Heterocyclic Chemistry
  • Place of Presentation: Glasgow
• [Presentation] 海洋産多環性ピロールアルカロイド類の合成と生理活性 (2011)
  • Author(s): 石橋郁人
  • Organizer: 日本農芸化学会支部総会・奨励賞受賞講演・特別講演会
  • Place of Presentation: 福岡
• [Presentation] 硫酸エステル型ピロールアルカロイドの合成研究 (2010)
  • Author(s): 森瀬崇大、石橋郁人
  • Organizer: 日本農芸化学会西日本支部大会
  • Place of Presentation: 熊本
  • Year and Date: 2010-09-18
• [Presentation] テロメラーゼ阻害活性物質ディクティオデンドリンAの合成研究 (2010)
  • Author(s): 吉永祐樹、石橋郁人
  • Organizer: 日本農芸化学会西日本支部大会
  • Place of Presentation: 熊本
  • Year and Date: 2010-09-18
• [Presentation] テロメラーゼ阻害活性物質ディクティオデンドリンBの合成 (2010)
  • Author(s): 平尾翔太郎、岩尾正倫、石橋郁人
  • Organizer: 日本農芸化学会2010年度大会
  • Place of Presentation: 東京大学駒場キャンパス(東京都)
  • Year and Date: 2010-03-28
• [Presentation] 硫酸エステル型ピロールアルカロイドの合成研究 (2010)
  • Author(s): 森瀬崇大、石橋郁人
  • Organizer: 日本農芸化学会西日本支部大会(第284回)
  • Place of Presentation: 熊本
• [Presentation] テロメラーゼ阻害活性物質ディクティオデンドリンAの合成研究 (2010)
  • Author(s): 吉永祐樹、平尾翔太郎、石橋郁人
  • Organizer: 日本農芸化学会西日本支部大会(第284回)
  • Place of Presentation: 熊本
• [Presentation] テロメラーゼ阻害活性物質ディクティオデンドリンBの合成 (2010)
  • Author(s): 平尾翔太郎、吉永祐樹、岩尾正倫、石橋郁人
  • Organizer: 日本農芸化学会2010年度大会
  • Place of Presentation: 東京
• [Presentation] テロメラーゼ阻害活性物質ディクティオデンドリンの合成研究 : 基本骨格化合物の合成 (2009)
  • Author(s): 平尾翔太郎、岩尾正倫、石橋郁人
  • Organizer: 第39回複素環化学討論会
  • Place of Presentation: さわやかちば県民プラザ(柏市)
  • Year and Date: 2009-10-14
• [Presentation] テロメラーゼ阻害活性物質ディクティオデンドリンの合成研究:基本骨格化合物の合成 (2009)
  • Author(s): 平尾翔太郎、岩尾正倫、石橋郁人
  • Organizer: 第39回複素環化学討論会
  • Place of Presentation: 千葉
• [Remarks]
  • URL: http://www2.fish.nagasaki-u.ac.jp/fish/kyoukan/isibasi/fi-j.htm
• [Remarks]
  • URL: http://www.fish.nagasaki-u.ac.jp/fish/kyoukan/isibasi/fi-j.html
• [Patent(Industrial Property Rights)] 抗癌活性化合物 (2012)
  • Inventor(s): 岩尾正倫、石橋郁人、福田勉、長谷川寛雄
  • Industrial Property Rights Holder: 国立大学法人長崎大学
  • Filing Date: 2012-01-17
  • Overseas
• [Patent(Industrial Property Rights)] 抗癌活性化合物 (2012)
  • Inventor(s): 岩尾正倫, 石橋郁人, 福田勉, 長谷川寛雄
  • Industrial Property Rights Holder: 国立大学法人長崎大学
  • Filing Date: 2012-01-17
  • Overseas
• [Patent(Industrial Property Rights)] ベンゾ[g][1]ベンゾピラノ[4,3-b]インドールー6(13H)-オン骨格を持つ抗癌活性化合物 (2011)
  • Inventor(s): 岩尾正倫、石橋郁人、福田勉
  • Industrial Property Rights Holder: 国立大学法人長崎大学
  • Industrial Property Number: 2011-007011
  • Filing Date: 2011-01-17