Development of practical supply of isoquinoline marine natural products to designate the creation of the new anticancer agents

• Project/Area Number: 16590019
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Chemical pharmacy
• Research Institution: Meiji Pharmaceutical University
• Principal Investigator: SAITO Naoki Meiji Pharmaceutical University, Professor, 教授 (80142545)
• Project Period (FY): 2004 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥2,700,000 (Direct Cost: ¥2,700,000); Fiscal Year 2005: ¥1,100,000 (Direct Cost: ¥1,100,000); Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
• Keywords: Marine Natural Product / Renieramycin / Jorunnamycin / Oxidative Degradation / Anticancer Agent / Structure Activity Relationship / Chemical Transformation / Isoquinoline Alkaloid / 創薬 / 海洋資源 / 天然物化学 / アルカロイド / 海綿 / ウミウシ / ジョルマイシン / 酸化的分解反応

Research Abstract

As a part of our search for new anticancer metabolites in the isolation and characterization of biologically active compounds from the Thai marine animals, we have succeeded to find blue sponges, Xestospongia sp. growing around Sichang Island in the Gulf of Thailand. We report the isolation and structure elucidation of renieramycin M as a major products pretreated marine animals with potassium cyanide in methanolic buffer solution. This is the first example for supply a gram scale of renieramycin type products from marine sources. Renieramycin M, which has potent strong cytotoxicity against several kinds of tumor cells, was easily transformed to jorumycin and renieramycin J, independently. We discovered that the oxidative degradation of jorumycin and renieramycin E to generate simple isoquinoline alkaloids, such as mimosamycin, renierone, and renierol acetate. Furthermore, jorunnamycins A-C, three novel cytotoxic renieramycin type compounds, were isolated from the Thai nudibranch, Jorunna funebris that was pretreated with potassium cyanide, along five known compounds. The structures of them ware elucidated from spectral data along with chemical transformation. Thus, renieramycins will be going up one of fascinated lead for development of new anticancer drug near future.

Research Products

• [Journal Article] Structure and chemical property of three new marine alkaloids from the nudibranch Jorunna funebris which lives through in the blue sponge (2005)
  • Author(s): Naoki Saito, et al.
  • Journal Title: Yakugaku Zasshi 125, Suppl.3 Pages: 262-265
• [Journal Article] Cheniistry of Renieramycins. Part 4. Synthesis of a simple Natural Marine Product, 6-Hydroxy-7-methoxyisoquinoline methanol (2004)
  • Author(s): Naoki Saito et al.
  • Journal Title: Chem. Pharm. Bull. 52 (2) Pages: 282-286
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Chemistry of Renieramycins. Part 5. Structure Elucidation of Renieramycin-Type Derivatives O, Q, R, and S from Thai Marine Sponge, Xestospongia Species Pretreated with Potassium Cyanide (2004)
  • Author(s): Surattana Amnuoypol et ml.
  • Journal Title: J. Nat. Prod. 67 (6) Pages: 1023-1028
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Chemistry of Renieramycins. Part 6. Transformation of Renieramycin M into Jorumycin and Renieramycin J including Oxidative Degradation Products, Mimosamycin, Renierone, and Renierol Acetate (2004)
  • Author(s): Naoki Saito et al.
  • Journal Title: Tetrahedron 60 (17) Pages: 3873-3881
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Chemistry of Renieramycins. Part 4. Synthesis of a Simple Natural Marine Product, 6-Hydroxy-7-methoxy-isoquinolinemethanol (2004)
  • Author(s): Saito, N., Tanaka, C., Satomi, T., Oyama, C., Kubo, A.
  • Journal Title: Chem.Pharm.Bull. 52(2) Pages: 282-286
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Chemistry of Renieramycins. Part 5. Structure Elucidation of Renieramycin Type Derivatives O, Q, R, and S from Thai Marne Sponge Xestospoigia Species Pretreated with Potassium Cyanide (2004)
  • Author(s): Amnuoypol S., Suwanborirux, K., Pummangura, S., Kubo, A., Tanaka, C., Saito, N.
  • Journal Title: J.Nat.Prod. 67(6) Pages: 1023-1028
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Chemistry of Renieramycins. Part 6. Transformation of Renieramycin M into Jorumycin and Renieramycin J including Oxidative Degradation Products, Mimosamycin, Renierone, and Renierol Acetate (2004)
  • Author(s): Saito, N., Tanaka, C., Koizumi, Y., Suwanborirux, K., Amnuoypol S., Kubo, A.
  • Journal Title: Tetrahedron 60(17) Pages: 3873-3881
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Chemistry oRenieramycins. Part 4. Synthesis of a Simple Natural Marine Product, 6-Hydroxy-7-methoxyisoquinolinemethanol (2004)
  • Author(s): Naoki Saito et al.
  • Journal Title: Chem.Pharm.Bull. 52(2) Pages: 282-286
• [Journal Article] Chemistry of Renieramycins. Part 5. Structure Elucidation of Renieramycin-Type Derivatives O, Q, R, and S from Thai Marine Sponge Xestospongia Species Pretreated with Potassium Cyanide (2004)
  • Author(s): Surattana Amnuoypol et al.
  • Journal Title: J.Nat.Prod. 67(6) Pages: 1023-1028
• [Journal Article] Chemistry of Renieramycins. Part 6 : Transformation of Renieramycin M into Jorumycin and Renieramycin J including Oxidative Degradation Products, Mimosamycin, Renierone, and Renierol Acetate (2004)
  • Author(s): Naoki Saito et al.
  • Journal Title: Tetrahedron 60 Pages: 3873-3881
• [Journal Article] Chemistry of Renieramycins. Part 3. Isolation and Structure of Stabilized Renieramycin Type Derivatives Possessing Activity from Thai Sponge, Xestospongia Species, Pretreated with Potassum Cyanide (2003)
  • Author(s): Khanit Suwanborirux et al.
  • Journal Title: J. Nat. Prod. 66 (11) Pages: 1441-1446
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Chemistry of Antitumor Isoquinoline Alkaloids. Unexpected Oxidation of Saframycin S to Generate Simple Isoquinoline Alkaloids, Mimocin and Mimosamycin (2003)
  • Author(s): Naoki Saito et al.
  • Journal Title: Heterocycles 61 (1) Pages: 79-86
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Chemistry of Renieramycins. Part 3. Isolation of Stabilized Renieramycin Type Derivatives Possessing Activity from Thai Sponge, Xestospoigia Species Pretreated with Potassium Cyanide (2003)
  • Author(s): Suwanborirux, K., Amnuoypol S., Plubrukarn, A., Pummangura, S., Kubo, A., Saito, N.
  • Journal Title: J.Nat.Prod. 66(11) Pages: 1441-1446
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Chemistry of Antitumor Isoquinoline Alkaloids : Unexpected Oxidation of Saframycin S to Generate Simple Isoquinoline Alkaloids, Mimosamycin and Momocin (2003)
  • Author(s): Saito, N., Koizumi, Y., Suwanborirux, K., Kubo, A.
  • Journal Title: Heterocycles 61(1) Pages: 79-86
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Jorunnamycins A-C Novel Cytotoxic Renieramycin Type Bistetrahydroisoquinolines isolated from the Thai Nudibranch Jorunna funebris
  • Author(s): Korunvika Charupant et al.
  • Journal Title: J. Nat. Prod. (in press)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Jorunnamycins A-C, Novel Cytotoxic Renieramycin Type Bistetrahydroisoquinolines isolate from the Thai Nudibranch Jorunna funebris
  • Author(s): Charupant K., Kuwanborirux K., Amnuoypol, S., Saito, E., Kubo, A., Saito, N.
  • Journal Title: J.Nat.Prod. (submitted)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Renieramycins, their isolation from Xestospongia species, and anticancer agents containing them.
  • Author(s): Kubo, A., Saito, N., Pummangura, S., Suwanborirux, K.
  • Journal Title: Jpn.Kokai Tokkyo Koho, JP 2004231552 A2 20040819(Priority Application : JP 2003-20821
  • Description: 「研究成果報告書概要(欧文)」より
• [Patent(Industrial Property Rights)] 新規レニエラマイシン系化合物、その取得方法およびその用途 (2003)
  • Inventor(s): 久保陽徳, 齋藤直樹, スニポーン・プマングーラ, カニ・スワンボリラック
  • Industrial Property Rights Holder: 久保陽徳
  • Filing Date: 2003-01-29
  • Acquisition Date: 2004-08-19
  • Description: 「研究成果報告書概要(和文)」より