Design, Synthesis, and Structure-Activity Relationship Study of Novel Neuro-Protecting Drugs Based on Natural Product Hybridization

• Project/Area Number: 25460010
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Chemical pharmacy
• Research Institution: University of Toyama
• Principal Investigator: Matsuya Yuji 富山大学, 大学院医学薬学研究部(薬学), 教授 (50255858)
• Co-Investigator(Renkei-kenkyūsha): SUGIMOTO KENJI 富山大学, 大学院医学薬学研究部, 准教授 (60400264) ; TOHDA CHIHIRO 富山大学, 和漢医薬学総合研究所, 准教授 (10272931)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: ハイブリッド化 / 天然物 / 神経賦活作用 / カップリング反応 / ハブリッド化 / デノソミン

Outline of Final Research Achievements

Novel hybridization compounds between steroidal natural product "denosomin" and its potential molecular target receptor "vitamin D3" were designed for the purpose of development of novel neuro-protecting agent toward Alzheimer disease chemotherapy. The syntheses were achieved by means of convergent synthetic strategy using palladium-catalyzed coupling reactions. The synthesized hybrid compounds were subjected to assay for their neuro-protecting activity, and new derivatives showing more potent activity than positive control compound "denosomin" were discovered.

Research Products

• [Journal Article] Synthesis of Denosomin-Vitamin D3 Hybrids and Evaluation of their Anti-Alzheimer’s Disease Activities. (2015)
  • Author(s): Sugimoto K, Yajima H, Hayashi Y, Minato D, Terasaki S, Tohda C, Matsuya Y.
  • Journal Title: Organic Lett. Volume: 17(23) Issue: 23 Pages: 5910-5913
  • DOI: 10.1021/acs.orglett.5b03138
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] アルツハイマー症治療薬開発を指向した Denosomin-Vitamin D3 ハイブリッドの設計と合成 (2016)
  • Author(s): 村田 賢信, 矢島 久成, 林 祐介, 湊 大志郎, 寺崎 紗有里, 杉本 健士, 東田 千尋, 松谷裕二
  • Organizer: 日本薬学会第１３６年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-03-27
• [Presentation] Design, synthesis, and biological evaluation of promising anti-Alzheimer’s compounds having dihydropyrone unit as a key component. (2015)
  • Author(s): Sugimoto K, Yajima H, Tohda C, Matsuya Y.
  • Organizer: The XVI International Conference on Heterocycles in Bioorganic Chemistry
  • Place of Presentation: Metz (France)
  • Year and Date: 2015-06-08
  • Int'l Joint Research
• [Presentation] 創薬に生かされている化学 (2014)
  • Author(s): 松谷裕二
  • Organizer: 高教研大会化学部会
  • Place of Presentation: 富山
  • Year and Date: 2014-10-02
  • Invited
• [Presentation] 生理活性天然物を基盤とした分子設計と有機合成 (2014)
  • Author(s): 松谷裕二
  • Organizer: 東邦大学特別セミナー講演会
  • Place of Presentation: 千葉
  • Year and Date: 2014-06-14
  • Invited
• [Presentation] 新規神経系賦活薬創成を目指したデノソミン-Vitamin D3ハイブリッドの合成 (2013)
  • Author(s): 矢島久成，杉本健士，東田千尋，湊大志郎，松谷裕二
  • Organizer: 有機合成化学北陸セミナー
  • Place of Presentation: 金沢
• [Presentation] デノソミン－VD3ハイブリッドの設計と合成を基盤とした新規アルツハイマー治療薬の開発研究 (2013)
  • Author(s): 矢島久成，杉本健士，湊大志郎，東田千尋，松谷裕二
  • Organizer: 第43回複素環化学討論会
  • Place of Presentation: 岐阜