Research on seeds from unique ring skeletal limonoids for drug discovery

• Project/Area Number: 16K08309
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Natural medicines
• Research Institution: Hoshi University
• Principal Investigator: Morita Hiroshi 星薬科大学, 薬学部, 教授 (70220069)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: リモノイド / ceramicine B / 脂肪滴蓄積抑制作用 / メラニン産生抑制作用 / ceramicine / センダン科 / 脂肪細胞分化抑制 / 薬学 / 天然活性物質

Outline of Final Research Achievements

During our search for bioactive limonoids from medicinal plants, we have isolated ceramicines, which are a series of limonoids from the bark of Chisocheton ceramicus (Meliaceae). Ceramicine B has shown a strong lipid droplets accumulation (LDA) inhibitory activity and also anti-melanin deposition activity.
With the purpose of discovering compounds with stronger activity than ceramicine B, we further investigated the constituents of C. ceramicus. As a result, several new ceramicines were isolated, and their structures were determined on the basis of spectroscopic analyses. We also investigated the effect of the substituent by synthesizing several derivatives and evaluating their LDA inhibitory activity. Furthermore, some new limonoids from Walsura chrysogyne and Chukrasia velutina, were isolated and their structures were elucidated.

Academic Significance and Societal Importance of the Research Achievements

これまでリモノイド類の作用として着目されてこなかったメラニン産生抑制作用および脂肪滴蓄積抑制作用の作用機序を解明する。これらの作用機序を解明することにより、特に ceramicine類の活性の本質を解明する。また、Chisocheton ceramicus に主成分として含有されるceramicine B を利用して、構造変換を行うことにより、新たな創薬素材分子を設計する。さらに、熱帯未利用植物抽出エキスをスクリーニングすることで、特異的な環骨格を有するリモノイドの探索を行い天然物特有の多様性に富んだ新規創薬シードを見出す。

Research Products

• [Int'l Joint Research] Malaya University/Faculty of Science(マレーシア)
• [Journal Article] Ceramicines M-P from Chisocheton ceramicus: isolation and structure-activity relationship study (2018)
  • Author(s): Alfarius Eko Nugroho, Akiyo Hashimoto, Chin-Piow Wong, Hiromasa Yokoe, Masayoshi Tsubuki, Toshio Kaneda, A. Hamid A. Hadi, Hiroshi Morita
  • Journal Title: J. Nat. Med. Volume: 72 Issue: 1 Pages: 64-72
  • DOI: 10.1007/s11418-017-1109-2
  • NAID: 40021455888
  • Peer Reviewed
• [Presentation] センダン科 Chisocheton ceramicus の成分研究 (2018)
  • Author(s): Alfarius Eko Nugroho,吉川夏生，岡部真理佳，小室智之，Chin Piow Wong，平澤祐介，金田利夫，A. Hamid A. Hadi，森田博史
  • Organizer: 日本生薬学会第65回年会
• [Presentation] センダン科 Chukrasia velutina の成分探索 (2018)
  • Author(s): 丹下雅貴，日下部寿美，Alfarius Eko Nugroho，平澤祐介，金田利夫，松野倫代，幾井康仁，森田博史
  • Organizer: 日本生薬学会第65回年会
• [Presentation] センダン科 Chisocheton ceramics の成分研究 (2017)
  • Author(s): 吉川夏生、岡部真里佳、Alfarius Eko Nugroho 、小室智之、Chin Piow Wong 、平澤祐介 、金田利夫、A.Hamid A. Hadi、森田博史
  • Organizer: 日本生薬学会
• [Presentation] Ceramicine Bの脂肪細胞分化に対する抑制作用 (2016)
  • Author(s): 万行智愛季、Chin Piow Wong 、Alfarius Eko Nugroho 、飯塚菜々子、金田利夫、森田博史
  • Organizer: 日本生薬学会
  • Place of Presentation: 富山国際会議場
  • Year and Date: 2016-09-24