Development for medicinal chemistry on antitumor isoquinoline marine natural products as lead compound

2013 Fiscal Year Final Research Report

• Project/Area Number: 23590019
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Chemical pharmacy
• Research Institution: Meiji Pharmaceutical University
• Principal Investigator: SAITO NAOKI 明治薬科大学, 薬学部, 教授 (80142545)
• Co-Investigator(Kenkyū-buntansha): YOKOYA Masashi 明治薬科大学, 薬学部, 助教 (50338539)
• Project Period (FY): 2011 – 2013
• Keywords: 海洋天然物 / 抗腫瘍活性 / イソキノリン / 国際共同研究 / 構造解析 / 全合成 / エクチナサイジン / レニエラマイシン

Research Abstract

In the course of our research on new metabolites, which involves the isolation and characterization of biologically active compounds and the preparation of their respective alnalogues, we can isolate several new marine isoquinolines, such as renieramycin V-Y from blue sponges. The second, we are succeeded to the total syntheses of renieramycin G and cribrstatin 4. Furthermore, many model compounds of the left half of renieramycins were prepared from phenylalanine derivatives. The initial cytotoxicity profiles of natural products and their derivatives along with synthetic analogues are also presented.

Research Products

• [Journal Article] Plonthip Puthongking, Khanit Suwanborirux, Naoki Saito, Isolation, Structure Characterization and Synthesis of Stabilized 1,2,3,4-tetrahydroisoquinoline Marine Natural Product from Potassium Cyanide Pretreated Thai Tuncate, Ecteinascidia thurstoni (2014)
  • Author(s): Shinya Kimura, Waree Pangkruang, Masashi Yokoya, Amane Honda
  • Journal Title: Heterocycles Volume: 88 Pages: 363-375
  • DOI: 10.3987/COM-13-S(S)32
  • Peer Reviewed
• [Journal Article] Chemistry of Ecteinascidins. Part 4. Preparation of 2'-N-Acyl Ecteinascidin 770 Derivatives with Improved Cytotoxicity Profiles (2013)
  • Author(s): Mitsuhiro Tsujimoto, Witaya Lowtangkitcharoen, Nanae Mori, Waree Pangkruang, Ploenthip Puthongking, Khanit Suwanborirux, Naoki Saito
  • Journal Title: Chem Pharm. Bull Volume: 61 Pages: 1052-1064
  • URL: https://www.jstage.jst.go.jp/article/cpb/61/10/61_c13-00525/_pdf
  • Peer Reviewed
• [Journal Article] Replacement of a Quinone by 5-O-Acetylhydroquinone Abolishes the Accidental Necrosis Inducing Effect While Preserving theApoptosis-Inducing Effect of Renieramycin M on Lung Cancer Cells (2013)
  • Author(s): Thaniwan Cheun-Arom, Pithi Chanvorachote, Natchanun Sirimangkalakitti, Takushina Chuanasa, Naoki Saito, Ikuo Abe, Khanit Suwanborirux
  • Journal Title: J. Nat. Prod Volume: 76 Pages: 1468-1474
  • DOI: 10.121/np400277m
  • Peer Reviewed
• [Journal Article] Preparation of Tricyclic Lactam Model Compounds of Renieramycin and Saframycin Anticancer natural Products from Common Intermediate (2013)
  • Author(s): Keiyo Nakai, Masashi Yokoya, Naoki Saito
  • Journal Title: Chem. Pharm. Bull Volume: 61 Pages: 853-869
  • URL: https://www.jstage.jst.go.jp/article/cpb/61/8/61_c13-00361/_pdf
  • Peer Reviewed
• [Journal Article] Ecteinascidin 770, a Tetrahydroisoquinoline Alkaloid, Sensitizees human lung Cancer Cells to Anoikis (2013)
  • Author(s): Phattrakorn Powan, Naoki Saito, Khanit Suwanborirux, Pithi Chanvorachote
  • Journal Title: Anticancer Res Volume: 33 Pages: 505-512
  • URL: http://ar.iiarjournals.org/content/33/2/505.full.pdf+html
  • Peer Reviewed
• [Journal Article] (2012)
  • Author(s): Mari Tatsukawa, Louvy Lynn C.Punzalan,Hilbert D. S. Magpantay, Irene M. Villasenñr, Gisela P. Concepcion, Khanit Suwanborirux, Masashi Yokoya, Naoki Saito
  • Journal Title: Tetrahedron Volume: 68 Pages: 7422-7428
  • DOI: 10.1016/j.tet.2012.06.067
  • Peer Reviewed
• [Journal Article] Selenium Oxide Oxidation of Hexahydro-1,5-imino-3-benzazocine-7,10-dione in Aliphatic Alcohol for Conversion of Renieramycin Marine Natural Products (2012)
  • Author(s): Mayuko Mori, Naomi Daikuhara, Junya Yamada, Naoki Saito
  • Journal Title: Heterocycles Volume: 86 Pages: 317-330
  • DOI: 10.3987/COM-12-S(N)12
  • Peer Reviewed
• [Journal Article] Chemistry of Renieramycins. Part 12. An Improved Total Synthesis of (±)-Renieramycin G (2012)
  • Author(s): Masashi Yokoya, Kimiko Shinada-Fujino, Saiko Masahiro Mimura, Yoshida, Hiroki Takada, Naoki Saito
  • Journal Title: Tetrahedron Volume: 68 Pages: 4166-4181
  • DOI: 10.1016/j.tet.2012.03.105
  • Peer Reviewed
• [Journal Article] Molecular Network Profiling of U373MG Human Glioblastoma Cells Following Induction of Apoptosis by Novel Marine-derived Anti-cancer 1,2,3,4-Tetrahydroisoquinoline Alkaloids (2012)
  • Author(s): Hiroko Tabunoki, Naoki Saito, Khanit Suwanborirux, Kornvika Charupant, Jun-ichi Satoh
  • Journal Title: Cancer Cell Int Volume: 12:14 Pages: 1-14
  • DOI: 10.1186/1475-2867-12-14
  • Peer Reviewed
• [Journal Article] Chemistry of Renieramycins. Part 10. Structure of Renieramycin V, A Novel Renieramycin Marine Natural Product Having a Sterol Ether at C-14 position (2012)
  • Author(s): Naoki Saito, Miho Yoshino, Kornvika Charupant, Khanit Suwanborirux
  • Journal Title: Heterocycles Volume: 84 Pages: 309-314
  • DOI: 10.3987/COM-11-S(P)28
  • Peer Reviewed
• [Journal Article] Chemistry of Renieramycins. Part 11. Total Synthesis of (±)-Cribrostatin 4 (2011)
  • Author(s): Masashi Yokoya, Hiroshi Ito, Naoki Saito
  • Journal Title: Tetrahedron Volume: 67 Pages: 9185-9192
  • DOI: 10.1016/j.tet.2011.09.076
  • Peer Reviewed
• [Journal Article] Chemistry of Ecteinascidins. Part 3. Preparation of 2'-N-Acyl Derivatives of Ecteinascidin 770 and Evaluation of Cytotoxicity (2011)
  • Author(s): Panithi Saktrakulkula, Satoru Toriumi, Masahiro Tsujimoto, Chamunan Patarapanich, Khanit Suwanborirux, Naoki Saito
  • Journal Title: Bioorg. & Med. Chem Volume: 19 Pages: 4421-4436
  • DOI: 10.1016/j.bmc.2011.06.04
  • Peer Reviewed
• [Journal Article] Synthesis of Renieramycins. Construction of the Core Ring System of Cribrostatin 4 Trough Modified Pictet-Spengler Cyclization of 3,6-Bisarylpiperazine-2,5-Dione with Diethoxyethyl Benzoate (2011)
  • Author(s): Masashi Yokoya, Hiroshi Ito, Naoki Saito
  • Journal Title: Chem. Pharm. Bull Volume: 59 Pages: 787-792
  • URL: https://www.jstage.jst.go.jp/article/cpb/59/6/59_6_787/_pdf
• [Journal Article] Chemistry of Renieramycins. Part 9. Stereocontrolled Total Synthesis of (±)-Renieramycin G (2011)
  • Author(s): Masashi Yokoya, Kimiko Shinada-Fujino, Naoki Saito
  • Journal Title: Tetrahedron Lett Volume: 52 Pages: 2446-2449
  • DOI: 10,1016/j.tetlet.2011.02.055
  • Peer Reviewed
• [Presentation] エクチナサイジン海洋天然物の化学修飾と生物活性評価 (2014)
  • Author(s): 森ななえ、辻本光宏、Witaya Lowtangkitcharoen, Khanit Suwanborirux, 齋藤直樹
  • Organizer: 日本薬学会第134 年会
  • Place of Presentation: 熊本
  • Year and Date: 2014-03-29
• [Presentation] レニエラマイシン右半部モデル化合物の合成と生物活性評価 (2014)
  • Author(s): 中井啓陽、久保圭司、横屋正志、齋藤直樹
  • Organizer: 日本薬学会第134 年会
  • Place of Presentation: 熊本
  • Year and Date: 2014-03-28
• [Presentation] 抗腫瘍活性テトラヒドロイソキノリン天然物の合成―共通中間体から左半部モデル化合物の合成 (2013)
  • Author(s): 中井啓陽、久保圭司、中山梨乃、横屋正志、齋藤直樹
  • Organizer: 第39回反応と合成の進歩シンポジウム
  • Place of Presentation: 福岡
  • Year and Date: 2013-11-05
• [Presentation] タイ国に生息する海洋生物由来アルカロイドを創薬リードとする化学的研究 (2013)
  • Author(s): 齋藤直樹
  • Organizer: 第57回日本薬学会関東支部大会
  • Place of Presentation: 東京
  • Year and Date: 2013-10-26
  • Invited
• [Presentation] Chemistry of Ecteinascidin Marine Natural Products. Preparation of 2'-N-Acyl Derivatives of Ecteinascidin 770 and Evaluation of Cytotoxicity (2013)
  • Author(s): Naoki Saito, Mitsuhiko Tsujimoto, Nanae Mori, Waree Pangkruang, Proenthip Puthongking, Witaya Lowtangkitcharoen, Khanit Suwanborirux
  • Organizer: The 9^<th> FMC International Chemistry Symposium (AIMECS13)
  • Place of Presentation: Taipei (Taiwan)
  • Year and Date: 2013-10-17
• [Presentation] 抗腫瘍活性天然物レニエラマイシンM の全合成 (2013)
  • Author(s): 高田裕樹、三村政博、横屋正志、齋藤直樹
  • Organizer: 日本薬学会第133 年会
  • Place of Presentation: 横浜
  • Year and Date: 2013-03-29
• [Presentation] 青色海綿由来イソキノリン海洋天然物の全合成研究 (2012)
  • Author(s): 横屋正志、伊藤裕史、齋藤直樹
  • Organizer: 第37回反応と合成の進歩シンポジウム
  • Place of Presentation: 徳島
  • Year and Date: 2012-11-07
• [Presentation] レニエラマイシン海洋天然物の化学的研究:右半部モデルの二酸化セレン酸化による5位への酸素官能基の立体選択的導入 (2012)
  • Author(s): 森麻悠子、大工原直美、齋藤直樹
  • Organizer: 第38回反応と合成の進歩シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2012-11-05
• [Presentation] Chemistry of Renieramycin Antitumor Marine Natural Products. An Improved Total Synthesis of (±)-Renieramycin G (2012)
  • Author(s): Naoki Saito, Kimiko Shinada-Fujuno, Masashi Yokoya
  • Organizer: 15^<th> tetrahedron Symposium
  • Place of Presentation: Amsterdam (the Netherlands)
  • Year and Date: 2012-06-27
• [Presentation] フィリピンに生息する青色海綿由来天然物の構造 (2012)
  • Author(s): 辰川真理、平出裕美、齋藤直樹、Hirbert D. S. Magpantay, Louvy L. C. Punzalan, Gisela P. Concepcion
  • Organizer: 日本薬学会第132 年会
  • Place of Presentation: 札幌
  • Year and Date: 2012-03-31
• [Presentation] Chemistry of Ecteinascidin Marine Natural Products: Synthesis of 6'-O- and 2'-N-Acyl Derivatives of Ecteinascidin 770 for Evaluation of Cytotoxicity (2011)
  • Author(s): Naoki Saito, Satoru Toriumu, Mitsuhiro Tsujimoto, Panithi Saktrakulkla, Khanit Suwanborirux
  • Organizer: 8^<th> FMC International Chemistry Symposium (AIMECS11)
  • Place of Presentation: Tokyo (Japan)
  • Year and Date: 2011-12-02
• [Remarks]
  • URL: http://www.my-pharm.ac.jp/pcns6mpu/wordpress/
• [Remarks] 森ななえ、辻本光宏、ビタヤ・ロタンチャローン、カニ・スワンボリラック、齋藤直樹、タイ国に生息する群体ホヤ由来エクチナサイジン海洋天然物の抗腫瘍活性増強を目指した合成研究、第3 回CSJ 化学フェスタ、平成25 年10 月23 日、東京
• [Remarks] 齋藤直樹、アジア圏に生息する海洋生物由来新規制癌剤の開発、イノベーシュン・ジャパン(大学見本市)、平成25 年8 月29-30日、東京ビックサイト