Natural Products based Chemical Biology for Regenerative Medicine

2010 Fiscal Year Final Research Report

• Project/Area Number: 20681021
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Living organism molecular science
• Research Institution: Chiba University
• Principal Investigator: ARAI A.Midori Chiba University, 大学院・薬学研究院, 准教授 (40373261)
• Project Period (FY): 2008 – 2010
• Keywords: ケミカルバイオロジー / 天然物 / 有機化学 / 再生医療 / 神経幹細胞

Research Abstract

We have developed "protein- and cell-based screen methods" to find regenerative medicine of neuron. Several active natural products were isolated, which act on transcriptional factors in neural stem cells. Moreover, from synthetic compound library based on natural products several new active compounds were found.

Research Products

• [Journal Article] Approaches to Neural Stem Cells and Cancer Cells based on Natural Products (2011)
  • Author(s): Arai, M.A.
  • Journal Title: Chem.Pharm.Bull. 59 Pages: 417-426
  • Peer Reviewed
• [Journal Article] New Hedgehog/GLI-signaling inhibitors from Adenium obesum (2011)
  • Author(s): Arai, M.A., Tateno, C., Koyano, T., Kowithayakorn, T., Kawabe, S., Ishibashi, M.
  • Journal Title: Org.Biomol.Chem. 9 Pages: 1133-1139
  • Peer Reviewed
• [Journal Article] Total synthesis and evaluation of Wnt signal inhibition of melleumin A, B and their derivatives (2011)
  • Author(s): Arai, M.A., Hanazawa, S., Uchino, Y., Li, X., Ishibashi, M.
  • Journal Title: Org.Biomol.Chem. 8 Pages: 5285-5293
  • Peer Reviewed
• [Journal Article] Tubiferic acid, a new 9,10-secocycloartane triterpenoid acid isolated from the myxomycete (2011)
  • Author(s): Ippongi, Y., Ohtsuki, T., Toume, K., Arai, M.A., Yamamoto, Y., Ishibashi, M.
  • Journal Title: Tubulifera arachnoidea, Chem.Pharm.Bull. 59 Pages: 279-281
  • Peer Reviewed
• [Journal Article] New Hedgehog/GLI signaling inhibitors from Excoecaria agallocha (2010)
  • Author(s): Rifai, Y., Arai, M.A., Sadhu, S.K., Ahmed, F., Ishibashi, M.
  • Journal Title: Bioorg.Med.Chem.Lett. 21 Pages: 718-722
  • Peer Reviewed
• [Journal Article] Practical Total Synthesis of Fuligocandins A, B (2010)
  • Author(s): Arai, M.A., Seto, J., Ahmed, F., Uchiyama, K., Ishibashi, M.
  • Journal Title: Synlett 16 Pages: 2498-2502
  • Peer Reviewed
• [Journal Article] Constituents of Amoora cucullata with TRAIL resistance overcoming activity (2010)
  • Author(s): Ahmed, F., Toume, K., Sadhu, S.K., Ohtsuki, T., Arai, M.A., Ishibashi, M.
  • Journal Title: Org.Biomol.Chem. 8 Pages: 3696-3703
  • Peer Reviewed
• [Journal Article] Terpenoids and flavonoid glycoside from Acacia pennata as Hedgehog/GLI-mediated transcriptional inhibitors (2010)
  • Author(s): Rifai, Y., Arai, M.A., Koyano, T., Kowithayakorn, T., Ishibashi, M.
  • Journal Title: J.Nat.Prod. 73 Pages: 995-997
  • Peer Reviewed
• [Journal Article] A Method for the Rapid Discovery of Naturally Occurring Products using Proteins Immobilized on Magnetic Beads and Reverse Affinity Chromatography (2009)
  • Author(s): Arai, M.A., Kobatake, E., Koyano, T., Kowithayakorn, T., Kato, S., Ishibashi, M.
  • Journal Title: Chem.Asian J. 4 Pages: 1802-1808
  • Peer Reviewed
• [Journal Article] The first Hes1 dimer inhibitors from natural products (2009)
  • Author(s): Arai, M.A., Masada, A., Ohtsuka, T., Kageyama, R., Ishibashi, M.
  • Journal Title: Bioorg.Med.Chem.Lett. 19 Pages: 5778-5781
  • Peer Reviewed
• [Journal Article] Search for Bioactive Natural Products Targeting Cancer-Related Signaling Pathways (2009)
  • Author(s): Ishibashi, M., Arai, M.A.
  • Journal Title: J.Synth.Org.Chem., Jpn. 67 Pages: 1094-1104
• [Journal Article] 天然物を基盤とするWntおよびHedgehogシグナル阻害剤の探索 (2009)
  • Author(s): 荒井緑, 石橋正己
  • Journal Title: ファルマシア 45 Pages: 197-202
• [Journal Article] Naturally Occurring Small-molecule Inhibitors of Hedgehog/GLI-mediated Transcription (2008)
  • Author(s): Hosoya, T., Arai, M.A., Koyano, T., Kowithayakorn, T., Ishibashi, M.
  • Journal Title: ChemBioChem 9 Pages: 1082-1092
  • Peer Reviewed
• [Journal Article] Hedgehog/GLI-mediated transcriptional inhibitors from Zizyphus cambodiana (2008)
  • Author(s): Arai, M.A., Tateno, C., Hosoya, T., Koyano, T., Kowithayakorn, T., Ishibashi, M.
  • Journal Title: Bioorg.Med.Chem. 16 Pages: 9420-9424
  • Peer Reviewed
• [Journal Article] Efficient Synthesis of Chromone and Flavonoid Derivatives with Diverse Heterocyclic Units (2008)
  • Author(s): Arai, M.A., Sato, M., Sawada, K., Hosoya, T., Masami Ishibashi, M.
  • Journal Title: Chem.Asian J. 3 Pages: 2056-2064
  • Peer Reviewed
• [Journal Article] Synthesis and Evaluation of Isomers of Melleumin B from the Myxomycete Physarum melleum ; An Approach for Wnt Signal Inhibitor Trusted in Nature (2008)
  • Author(s): Arai, M.A., Uchino, Y., Hanazawa, S.Li, X., Kimura, N., Ishibashi, M.
  • Journal Title: Heterocycles 76 Pages: 1425-1438
  • Peer Reviewed
• [Journal Article] Determination of absolute stereochemistry, total synthesis, and evaluation of peptides from the myxomycete (2008)
  • Author(s): Hanazawa, S., Arai, M.A., Li, X., Ishibashi, M.
  • Journal Title: Physarum melleum, Bioorg.Med.Chem.Lett. 18 Pages: 95-98
  • Peer Reviewed
• [Presentation] 天然物を基盤とした神経幹細胞,癌細胞へのアプローチ (2011)
  • Author(s): 荒井緑
  • Organizer: 第27回「ケミカルバイオロジー研究領域」勉強会(理研セミナー)(招待講演)
  • Place of Presentation: 理化学研究所和光本所
  • Year and Date: 2011-02-23
• [Presentation] Chromone and flavonoid library with diverse heterocyclic units and their bioactivity on neural stem cells (2010)
  • Author(s): M.A.Arai, N.Yanase Maekawa, M.Ishibashi
  • Organizer: Pacifichem 2010
  • Place of Presentation: Honolulu, U.S.A.
  • Year and Date: 2010-12-18
• [Presentation] Hedgehog/GLI Signaling Inhibitors from Acacia pennata and Excoecaria agallocha (2010)
  • Author(s): Y.Rifai, M.A.Arai, S.K.Sadhu, T.Koyano, T.Kowithayakorn, M.Ishibashi
  • Organizer: 第18回天然薬物の開発と応用シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2010-11-12
• [Presentation] 変形菌Tubulifera arachnoidea由来新規トリテルペンTA1の立体化学の決定 (2010)
  • Author(s): 石井健祐, 荒井緑, 一本木之人, 石橋正己
  • Organizer: 36回反応と合成の進歩シンポジウム
  • Place of Presentation: 名古屋
  • Year and Date: 2010-11-02
• [Presentation] 神経再生医薬を目指した「フラボノイド+ヘテロ環」ライブラリーの構築 (2010)
  • Author(s): 荒井緑, 柳瀬なつき, 小柳津和音, 石橋正己
  • Organizer: 第36回反応と合成の進歩シンポジウム
  • Place of Presentation: 名古屋
  • Year and Date: 2010-11-01
• [Presentation] 天然物骨格+複素環化合物の創製と生物活性 (2010)
  • Author(s): 荒井緑, 瀬戸淳也, 柳瀬なつき, 小柳津和音, 前川雄一, 内山健人, 石橋正己
  • Organizer: 第40回複素環化学討論会
  • Place of Presentation: 仙台
  • Year and Date: 2010-10-14
• [Presentation] チャームブレスレット型Hes1阻害剤の設計と合成 (2010)
  • Author(s): 荒井緑, 森實孟生, 石橋正己
  • Organizer: 第54回日本薬学会関東支部大会
  • Place of Presentation: 八王子
  • Year and Date: 2010-10-02
• [Presentation] TRAILシグナルを介してがん選択的にアポトーシスを誘導する天然物の探索 (2010)
  • Author(s): 當銘一文, Firoj Ahmed, 中澤孝文, 大槻崇, 荒井緑, 石橋正己
  • Organizer: 第52回天然有機化合物討論会
  • Place of Presentation: 静岡
  • Year and Date: 2010-09-30
• [Presentation] Butea superbaからの神経幹細胞で働く転写因子Ngn2誘導作用を指標とした天然物の探索 (2010)
  • Author(s): 荒井緑, 小柳津和音, 石橋正己, 大塚俊之, 影山龍一郎, 小谷野喬, T.Kowithayakorn
  • Organizer: 日本生薬学会第57年会
  • Place of Presentation: 徳島
  • Year and Date: 2010-09-25
• [Presentation] Approaches to neural stem cells based on natural products (2010)
  • Author(s): M.A.Arai
  • Organizer: The 1^<st> Joint Symposium on Pharmaceutical Sciences between College of Pharmacy, Seoul National University and Graduate School of Pharmaceutical Sciences, Chiba University(招待講演)
  • Place of Presentation: Chiba
  • Year and Date: 2010-08-27
• [Presentation] 天然物様化合物を軸とした神経幹細胞,癌細胞へのアプローチ (2010)
  • Author(s): 荒井緑
  • Organizer: 日本薬学会第130年会 奨励賞受賞講演(招待講演)
  • Place of Presentation: 岡山大学
  • Year and Date: 2010-03-29
• [Presentation] 天然物様化合物を軸とした癌細胞へのアプローチ (2010)
  • Author(s): 荒井緑
  • Organizer: 日本薬学会第130年会シンポジウム(招待講演)
  • Place of Presentation: 岡山
  • Year and Date: 2010-03-28
• [Presentation] 天然物様化合物を軸とした癌細胞へのアプローチ (2010)
  • Author(s): 荒井緑
  • Organizer: 日本薬学会第130年会 シンポジウム(招待講演)
  • Place of Presentation: 岡山大学
  • Year and Date: 2010-03-28
• [Presentation] 天然物様化合物を軸とした神経幹細胞,癌細胞へのアプローチ (2010)
  • Author(s): 荒井緑
  • Organizer: 理化学研究所理研シンポジウム(招待講演)
  • Place of Presentation: 理化学研究所和光本所
  • Year and Date: 2010-01-29
• [Presentation] 神経幹細胞を標的とする有用低分子の探索～天然物を基盤として～ (2009)
  • Author(s): 荒井緑
  • Organizer: 第28回メディシナルケミストリーシンポジウム 若手研究者シンポジウム「次世代創薬」(招待講演)
  • Place of Presentation: 東京
  • Year and Date: 2009-11-27
• [Presentation] Fuligocandin A,Bの合成と癌細胞のTRAIL耐性克服を目指した誘導体の合成 (2009)
  • Author(s): 荒井緑
  • Organizer: 第35回反応と合成の進歩シンポジウム
  • Place of Presentation: 金沢
  • Year and Date: 2009-11-15
• [Presentation] 脊髄損傷後の神経再生を目指した化合物の合成と活性評価 (2009)
  • Author(s): 荒井緑
  • Organizer: 第35回反応と合成の進歩シンポジウム
  • Place of Presentation: 金沢
  • Year and Date: 2009-11-15
• [Presentation] Approaches for discovery of naturally occurring products using immobilized proteins (2009)
  • Author(s): 荒井緑
  • Organizer: The 11th Intemational Kyoto Conference on New Aspects of Organic Chemistry
  • Place of Presentation: Nagoya
  • Year and Date: 2009-11-13
• [Presentation] 標的タンパク質相互作用を指標とした天然物探索 (2009)
  • Author(s): 荒井緑
  • Organizer: 第51回天然有機化合物討論会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-10-07
• [Presentation] 天然物骨格を基盤とする多様性化合物の効率的合成法と活性評価 (2008)
  • Author(s): 荒井緑
  • Organizer: 第38回複素環化学討論会
  • Place of Presentation: 福山
  • Year and Date: 2008-11-21
• [Presentation] タンデム型マイケルアルドール反応を利用した固相合成によるクロモン、フラボノイド誘導体のライブラリー構築研究 (2008)
  • Author(s): 荒井緑
  • Organizer: 第34回反応と合成の進歩シンポジウム
  • Place of Presentation: 京都
  • Year and Date: 2008-11-05
• [Presentation] 変形菌由来天然物メレウミン類の全合成研究とそのWntシグナル阻害活性 (2008)
  • Author(s): 荒井緑
  • Organizer: 第34回反応と合成の進歩シンポジウム
  • Place of Presentation: 京都
  • Year and Date: 2008-11-04
• [Presentation] Wntシグナル阻害剤の天然物を基盤とする開発研究 (2008)
  • Author(s): 荒井緑
  • Organizer: 第50回天然有機化合物討論会,2008
  • Place of Presentation: 福岡
  • Year and Date: 2008-10-02
• [Presentation] Wnt, Hedgehogシグナル阻害剤の探索と合成 (2008)
  • Author(s): 荒井緑
  • Organizer: モレキュラー・キラリティー2008
  • Place of Presentation: 岡山
  • Year and Date: 2008-05-23
• [Book] 千葉学ブックレット,千葉の健康6,薬学の世界をのぞく (2011)
  • Author(s): 荒井緑
  • Total Pages: 50-51
  • Publisher: 千葉日報社
• [Book] ソレル有機化学(下) (2009)
  • Author(s): 村田道雄, 石橋正己, 木越英夫, 佐々木誠, 荒井孝義, 荒井緑, 有本博一, 石橋正己, 及川雅人, 大石徹, 木越英夫, 北将樹, 此木敬一, 佐竹真幸, 佐々木誠, 末永聖武, 早川一郎, 松岡茂, 松森信明, 村田道雄
  • Total Pages: 645-675,759-785
  • Publisher: 東京化学同人
• [Remarks] ホームページ等
  • URL: http://www.p.chiba-u.ac.jp/lab/kouzou/index.html
• [Patent(Industrial Property Rights)] フラボノイト由来Hes1プロモーター阻害剤 (2010)
  • Inventor(s): 荒井緑・柳瀬なつき・小柳津和音・石橋正己
  • Industrial Property Rights Holder: 千葉大学
  • Industrial Property Number: 特許,特願2010-167577
  • Filing Date: 2010-07-26