Studies of the mechanisms of action of neovibsanins toward the development of therapeutic agents for Alzheimer's disease

2013 Fiscal Year Final Research Report

• Project/Area Number: 23590033
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Chemical pharmacy
• Research Institution: Tokushima Bunri University
• Principal Investigator: IMAGAWA Hiroshi 徳島文理大学, 薬学部, 教授 (80279116)
• Project Period (FY): 2011 – 2013
• Keywords: 有機化学 / 生物活性 / アルツハイマー病 / 神経科学 / 薬学 / 光親和性標識

Research Abstract

Neovibsanins were originally isolated from Viburnum awabuki by Fukuyama and co-workers in 1996. These natural products were found to display neurite outgrowth activity in PC12 cells, suggesting neovibsanin-type compounds could be promising candidates for the development of novel therapeutic agents to treat Alzheimer-type dementia. However, the detailed mechanism for the activity is still unknown. We carried out the syntheses of several kinds of neovibsanin derivatives on the basis of the tricyclic acetal which is a minimum essential structure expressing the activity, to clarify the detailed structure-activity relationship of neovibsanins. As the results, it was revealed that the C11 of neovibsanin skeleton is a suitable position for the substitution with photoaffinity-functional group. On the basis of these knowledge, the synthesis of the photoaffinity-labeled neovibsanin derivative, which is useful in order to find the target molecules having an affinity for neovibsanin, was achieved.

Research Products

• [Journal Article] Novel inhibitor of bacterial sphingomyelinase, SMY-540, developed based on three-dimensional structure analysis (2013)
  • Author(s): M. Oda, H. Imagawa, R. Kato, K. Yabiku, T. Yoshikawa, T. Takemoto, H. Takahashi, H. Yamamoto, M. Nishizawa, J. Sakurai, M. Nagahama
  • Journal Title: J. Enzyme Inhib. Med. Chem Volume: (Ahead of Print) Pages: 1-8
• [Journal Article] Concise synthesis of a probe molecule enabling analysis and imaging of vizantin (2013)
  • Author(s): H. Yamamoto, M. Oda, M. Nakano, K. Yabiku, M. Shibutani, T. Nakanishi, M. Suenaga, M. Inoue, H. Imagawa, M. Nagahama, Y. Matsunaga, S. Himeno, K. Setsu, J. Sakurai, Nishizawa
  • Journal Title: Chem. Pharm. Bull Volume: 61(4) Pages: 452-459
• [Journal Article] Development of vizantin, a safe immunostimulant, based on the structure−activity relationship of trehalose-6,6′-dicorynomycolate (2013)
  • Author(s): H. Yamamoto, M. Oda, M. Nakano, N. Watanabe, K. Yabiku, M. Shibutani, M. Inoue, H. Imagawa, M. Nagahama, S. Himeno, K. Setsu, J. Sakurai, M. Nishizawa
  • Journal Title: J. Med. Chem Volume: 56 Pages: 381-385
• [Journal Article] Yellow pigments, fomitellanols A and B, and TBAF (1.5 eq) drimane sesquiterpenoids, cryptoporic acids P and Q, from fomitella fraxinea and their inhibitory activity against COX and 5-LO (2013)
  • Author(s): K. Yoshikawa, K. Koso, M. Shimomura, M. Tanaka, H. Yamamoto, H. Imagawa, S. Arihara, T. Hashimoto
  • Journal Title: Molecules Volume: 18 Pages: 4181-4191
• [Journal Article] Carbon-nitrogen bond formation between allyl silyl ether and hydrazide promoted by mercuric triflate catalyst (2012)
  • Author(s): Yamamoto, N. Yamasaki, S. Yoshidome, I. Sasaki, K. Namba, H. Imagawa, M. Nishizawa
  • Journal Title: Synlett Volume: 23(7) Pages: 1069-1073
• [Journal Article] A Carbaboranylmercuric Salt Catalyzed Reaction; Highly Regioselective Cycloisomerization of 1,3-Dienes (2012)
  • Author(s): Η. Yamamoto, I. Sasaki, S. Shiomi, N. Yamasaki, H. Imagawa
  • Journal Title: Org. Lett Volume: 14 (9) Pages: 2266-2269
• [Journal Article] Phenanthrene Derivatives from Cymbidium Great Flower Marie Laurencin and Their Biological Activities (2012)
  • Author(s): Κ.Yoshikawa, T. Ito, K. Iseki, C. Baba, H. Imagawa, Y. Yagi, H. Morita, Y. Asakawa, S. Kawano, T. Hashimoto
  • Journal Title: J. Natural Products Volume: 75(4) Pages: 605-609
• [Journal Article] Syntheses of Structurally-simplified and Fluorescently-labeled Neovibsanin Derivatives and Analysis of their Neurite Outgrowth Activity in PC12 cells (2012)
  • Author(s): H. Imagawa, H. Saijo, H. Yamaguchi, K. Maekawa, T. Kurisaki, H. Yamamoto, M. Nishizawa, M. Oda, M. Kabura, M. Nagahama, J. Sakurai, M. Kubo, M. Nakai, K. Makino, M. Ogata, H. Takahashi, Y. Fukuyama
  • Journal Title: Bioorg. Med. Chem. Lett Volume: 22 Pages: 2089-2093
• [Journal Article] Synthesis of Chiral and Modifiable Hexahydroxydiphenoyl Compounds (2011)
  • Author(s): Asakura, N.; Fujimoto, S.; Michihata, N.; Nishii, K.; Imagawa, H,; Yamada, H.
  • Journal Title: J. Org. Chem Volume: 76 Pages: 9711-9719
• [Journal Article] An Efficient Pyrrole Synthesis via Silaphenylmercuric Triflate-Catalyzed Cyclization of Homopropargyl Azides (2011)
  • Author(s): H. Yamamoto, I. Sasaki, M. Mitsutake, A. Karasudani, H. Imagawa, M. Nishizawa
  • Journal Title: Synlett Volume: (19) Pages: 2815-2818
• [Journal Article] Halichonines A, B, and C, Novel Sesquiterpene Alkaloids from the Marine Sponge Halichondria okadai Kadota (2011)
  • Author(s): O. Ohno, T. Chiba, S. Todoroki, H. Yoshimura, Maru, K. Maekawa, H. Imagawa, K. Yamada, A. Wakamiya, K. Suenaga, D. Uemura
  • Journal Title: Chem. Commun Volume: 47 Pages: 12453-12455
• [Journal Article] Intermolecular Amination of Allyl Alcohols with Sulfamates : Effective Utilization of Mercuric Catalyst (2011)
  • Author(s): H. Yamamoto, E. Ho, I. Sasaki, M. Mitsutake, Y. Takagi, H. Imagawa, M. Nishizawa
  • Journal Title: Eur. J. Org. Chem Pages: 2417-2420
• [Presentation] 光親和性標識を持つネオビブサニン誘導体の合成 (2014)
  • Author(s): 山口仁美,小松加奈,柳井翠,杉本実希子,葛西祐介,久保美和,山本博文,福山愛保,今川洋
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本
  • Year and Date: 20140327-30
• [Presentation] Syntheses of Structurally-simplified Neovibsanin Derivatives and Analysis of their Neurite Outgrowth Activity (2013)
  • Author(s): Hiroshi Imagawa, Hayato Saijo, Hitomi Yamaguchi, Ken Maekawa, Takahiro Kurisaki, Hirofumi Yamamoto, Mugio Nishizawa, Masataka Oda, Michiko Kabura, Masahiro Nagahama, Jun Sakurai, Miwa Kubo, Megumi Nakai, Kosho Makino, Mitsuko Ogata, Hironobu Takahashi, Yoshiyasu Fukuyama
  • Organizer: 23rd French-Japanese Symposium on medicinal and fine chemistry(第23回日仏医薬精密化学会議)
  • Place of Presentation: 長崎
  • Year and Date: 20130512-15
• [Presentation] 光親和性標識を持つネオビブサニン誘導体の合成研究 (2012)
  • Author(s): 今川洋,○山口仁美,前川健,杉本実希子,西條速人,栗崎貴啓,山本博文,西澤麦夫,小田真隆,永浜政博,櫻井純,久保美和,牧野宏章,福山愛保
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 札幌
  • Year and Date: 20120328-31