Comprehensive natural products study for development of small molecules targeting signaling pathways

2009 Fiscal Year Final Research Report

• Project/Area Number: 19310136
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Living organism molecular science
• Research Institution: Chiba University
• Principal Investigator: ISHIBASHI Masami Chiba University, 大学院・薬学研究院, 教授 (90212927)
• Co-Investigator(Kenkyū-buntansha): A. ARAI Midori 千葉大学, 大学院・薬学研究院, 准教授 (40373261) ; OHTSUKI Takashi 千葉大学, 大学院・薬学研究院, 助教 (30401011)
• Project Period (FY): 2007 – 2009
• Keywords: 天然物有機化学

Research Abstract

In our laboratory, we are interested in comprehensive natural products chemistry study based on search for bioactive small molecules from unexplored natural resources. We recently examined extracts of various natural resources including unexplored myxomycetes, marine organisms, as well as several medicinal plants collected in South Asia. Recently we are particularly interested in screening studies targeting TRAIL, Wnt, and Hedgehog signaling pathways which are related to cancer diseases. As a result of these screening programs we have isolated a number of new bioactive natural products and investigated their unique biological effects.

Research Products

• [Journal Article] Activity of mangosteen xanthones and teleocidin A-2 in death-receptor expression enhancement and tumor necrosis-factor related apoptosis-inducing ligand assays (2010)
  • Author(s): Kikuchi, H., Ohtsuki, T., Koyano, T., Kowithayakorn, T., Sakai, T., Ishibashi, M.
  • Journal Title: J.Nat.Prod. 73 Pages: 452-455
• [Journal Article] A method for the rapid discovery of naturally occurring products by 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
• [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
• [Journal Article] Death receptor 5 promoter-enhancing compounds isolated from Catimbium speciosum and their enhancement effect on TRAIL-induced apoptosis (2009)
  • Author(s): Ohtsuki, T., Kikuchi, H., Koyano, T., Kowithayakorn, T., Sakai, T., Ishibashi, M.
  • Journal Title: Bioorg.Med.Chem. 17 Pages: 6748-6754
• [Journal Article] Cardenolide glycosides of Thevetia peruviana and triterpenoid saponins of Sapindus emarginatus as TRAIL resistance-overcoming compounds (2009)
  • Author(s): Miyagawa, T., Ohtsuki, T., Koyano, T., Kowithayakorn, T., Ishibashi, M.
  • Journal Title: J.Nat.Prod. 72 Pages: 1507-1511
• [Journal Article] Cassaine diterpenoid dimers isolated from Erythrophleum succirubrum with TRAIL-resistance overcoming activity (2009)
  • Author(s): Miyagawa, T., Ohtsuki, T., Koyano, T., Kowithayakorn, T., Ishibashi, M.
  • Journal Title: Tetrahedron Lett. 50 Pages: 4658-4662
• [Journal Article] Fuligoic acid, a new yellow pigment with a chlorinated polyene-pyrone acid structure isolated from the myxomycete Fuligo septica f. flava (2009)
  • Author(s): Shintani, A., Ohtsuki, T., Yamamoto, Y., Hakamatsuka, T., Kawahara, N., Goda, Y., Ishibashi, M.
  • Journal Title: Tetrahedron Lett. 50 Pages: 3189-3190
• [Journal Article] Death receptor 5 targeting activity-guided isolation of isoflavones from Millettia brandisiana and Ardisia colorata and evaluation of ability to induce TRAIL-mediated apoptosis (2009)
  • Author(s): Kikuchi, H., Ohtsuki, T., Koyano, T., Kowithayakorn, T., Sakai, T., Ishibashi, M.
  • Journal Title: Bioorg.Med.Chem. 17 Pages: 1181-1186
• [Journal Article] New Wnt/β-catenin signaling inhibitors isolated from Eleutherine palmifolia (2009)
  • Author(s): Li, X., Ohtsuki, T., Koyano, T., Kowithayakorn, T., Ishibashi, M.
  • Journal Title: Chem.Asian J. 4 Pages: 540-547
• [Journal Article] Isolation of new carbamate-or pyridine-containing natural products, fuzanins A, B, C, and D from Kitasatospora sp. IFM10917 (2009)
  • Author(s): Aida, W., Ohtsuki, T., Li, X., Ishibashi, M.
  • Journal Title: Tetrahedron 65 Pages: 369-373
• [Journal Article] Two new cadinane sesquiterpenes from Curcuma parviflora (2009)
  • Author(s): Sadhu, S. K., Tamaki, M., Ohtsuki, T., Toume, K., Koyano, T., Kowithayakorn, T., Ishibashi, M.
  • Journal Title: J.Nat.Prod. 72 Pages: 782-783
• [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
• [Journal Article] Tyrosine derivatives isolated from Streptomyces sp. IFM 10937 in a screening program for TRAIL-resistance overcoming activity (2008)
  • Author(s): Ahmed, F., Ohtsuki, T., Aida, W., Ishibashi, M.
  • Journal Title: J.Nat.Prod. 71 Pages: 1963-1966
• [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., Ishibashi, M.
  • Journal Title: Chem.Asian J. 3 Pages: 2056-2064
• [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
• [Journal Article] A novel sesquiterpenoid dimer parviflorene F induces apoptosis by upregulating the expression of TRAIL-R2 and a caspase-dependent mechanism (2008)
  • Author(s): Ohtsuki, T., Tamaki, M., Toume, K., Ishibashi, M.
  • Journal Title: Bioorg.Med.Chem. 16 Pages: 1756-1763
• [Journal Article] Determination of absolute stereochemistry, total synthesis, and evaluation of peptides from the myxomycete Physarum melleum (2008)
  • Author(s): Hanazawa, S., Arai, M. A., Li, X., Ishibashi, M.
  • Journal Title: Bioorg.Med.Chem.Lett. 18 Pages: 95-98
• [Journal Article] Brandisianins A-F, isoflavonoids isolated from Millettia brandisiana in a screening program for death-receptor expression enhancement activity (2007)
  • Author(s): Kikuchi, H., Ohtsuki, T., Koyano, T., Kowithayakorn, T., Sakai, T., Ishibashi, M.
  • Journal Title: J.Nat.Prod. 70 Pages: 1910-1914
• [Journal Article] A novel natural compound, a cycloanthranilylproline-derivative (Fuligocandin B), sensitizes leukemia cells to TRAIL-induced apoptosis through 15d-PGJ_2 production (2007)
  • Author(s): Hasegawa, H., Yamada, Y., Komiyama, K., Hayashi, M., Ishibashi, M., Sunazuka, T., Izuhara, T., Sugahara, K., Tsuruda, K., Masuda, M., Takasu, N., Tsukasaki, K., Tomonaga, M., Kamihira, S.
  • Journal Title: Blood 110 Pages: 1664-1674
• [Journal Article] Synthesis, determination of stereochemistry, and evaluation of new bisindole alkaloids from the myxomycete Arcyria ferruginea ; an approach for Wnt signal inhibitor (2007)
  • Author(s): Kaniwa, K., Arai, M. A., Li, X., Ishibashi, M.
  • Journal Title: Bioorg.Med.Chem.Lett. 17 Pages: 4254-4257
• [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要旨集
  • Place of Presentation: 東京大学
  • Year and Date: 20090000
• [Presentation] Approaches for discovery of naturally occurring products using immobilized proteins (2009)
  • Author(s): Midori A. Arai, Masami Ishibashi
  • Organizer: The 11th International Kyoto Conference on New Aspects of Organic Chemistry
  • Place of Presentation: Kyoto
  • Year and Date: 20090000
• [Presentation] デス受容体誘導作用をもつ天然物の探索 : マンゴスチン (Garcinia mangostana), 月桃 (Catimbium speciosum) 等からの活性成分の単離とTRAIL耐性克服作用 (2009)
  • Author(s): 菊地博之, 大槻崇, 小谷野喬, Thaworn Kowithayakorn, 酒井敏行, 石橋正己
  • Organizer: 第3回食品薬学シンポジウム講演要旨集
  • Place of Presentation: 大阪
  • Year and Date: 20090000
• [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, 小畠英史, 正田亜矢子, 石橋正己
  • Organizer: 第51回天然有機化合物討論会講演要旨集
  • Place of Presentation: 名古屋
  • Year and Date: 20090000
• [Presentation] Excoecaria indica からの Wnt シグナルを活性化する天然物の探索 (2009)
  • Author(s): 山口達弘, 大槻崇, 李暁帆, Alok K. Paul, M. Iqbal Ahmed, Samir K. Sadhu, 石橋正己
  • Organizer: 日本薬学会第129年会講演要旨集
  • Place of Presentation: 京都
  • Year and Date: 20090000
• [Presentation] シグナル伝達分子を標的とする天然物の探索 (2009)
  • Author(s): 石橋正己
  • Organizer: 第7回機能性分子シンポジウム
  • Place of Presentation: 筑波大学
  • Year and Date: 2009-10-31
• [Presentation] 抗がん剤薬理活性化合物のスクリーニング―シグナル阻害を中心に (2009)
  • Author(s): 石橋正己
  • Organizer: 第1回ちばバイオ交流フォーラム
  • Place of Presentation: グリーンタワーホテル幕張
  • Year and Date: 2009-09-16
• [Presentation] 癌に関するシグナルを標的とした天然物の探索 (2009)
  • Author(s): 石橋正己
  • Organizer: 第3回日本化学会関東支部大会講演要旨集
  • Place of Presentation: 早稲田大学
  • Year and Date: 2009-09-04
• [Presentation] Hedgehog signaling inhibitors isolated from myxomycetes and a Solanaceae plant (2008)
  • Author(s): M. Ishibashi, T. Hosoya, C. Tateno, M. A. Arai
  • Organizer: 7th Joint Meeting of AFERP, ASP, GA, PSE & SIF (49th Annual Meeting of the American Society of Pharmacognosy)
  • Place of Presentation: Athens, Greece
  • Year and Date: 20080803-20080808
• [Presentation] Search for bioactive natural products targeting signaling molecules mainly related to cancer-diseases (2008)
  • Author(s): M. Ishibashi
  • Organizer: 4th Korea-Japan-China Joint Symposium on Pharmacognosy
  • Place of Presentation: Gangneung, Korea
  • Year and Date: 20080618-20080620
• [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, 佐藤未奈, 澤田圭輔, 細谷孝博, 森實孟生, 石橋正己
  • Organizer: 第38回複素環化学討論会講演要旨集
  • Place of Presentation: 福山
  • Year and Date: 20080000
• [Presentation] デス受容体誘導作用をもつ天然物の探索 : 新規イソフラボン等の単離とTRAIL耐性克服作用 (2008)
  • Author(s): 菊地博之, 大槻崇, 小谷野喬, T. Kowithayakorn, 酒井敏行, 石橋正己
  • Organizer: 第17回天然薬物の開発と応用シンポジウム講演要旨集
  • Place of Presentation: 福岡
  • Year and Date: 20080000
• [Presentation] Wnt シグナル阻害作用をもつ天然物の探索 (2008)
  • Author(s): 李暁帆, 大槻崇, 小谷野喬, T. Kowithayakorn, 石橋正己
  • Organizer: 第17回天然薬物の開発と応用シンポジウム講演要旨集
  • Place of Presentation: 福岡
  • Year and Date: 20080000
• [Presentation] Studies on natural constituents inducing expression of death receptor 5 (2008)
  • Author(s): T. Ohtsuki, H. Kikuchi, T. Sakai, M. Ishibashi
  • Organizer: 第67回日本癌学会学術総会要旨集
  • Place of Presentation: 名古屋
  • Year and Date: 20080000
• [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, 花澤修和, 内野祐次郎, 李暁帆, 沼田輝美, 杉光則子, 石橋正己
  • Organizer: 第50回天然有機化合物討論会講演要旨集
  • Place of Presentation: 福岡
  • Year and Date: 20080000
• [Presentation] Discovering the Hedgehog/GLI Signaling Inhibitor with Frameworks Trusted in Nature (2008)
  • Author(s): M. A. Arai, M. Ishibashi
  • Organizer: 第22回内藤コンファレンス・ケミカルバイオロジー[I]講演案旨集
  • Place of Presentation: 札幌
  • Year and Date: 20080000
• [Presentation] 熱帯植物由来のデスレセプター誘導作用をもつ天然物 (2008)
  • Author(s): 大槻崇, 菊地博之, 酒井敏行, 石橋正己
  • Organizer: 第12回がん分子標的治療研究会学術総会抄録集
  • Place of Presentation: 東京
  • Year and Date: 20080000
• [Presentation] Wnt, Hedgehog シグナル阻害剤の探索と合成 (2008)
  • Author(s): 荒井緑, 石橋正己
  • Organizer: シンポジウムモレキュラー・キラリティー2008
  • Place of Presentation: 岡山
  • Year and Date: 20080000
• [Presentation] Wnt, Hedgehog シグナル阻害剤の天然物からの探索と合成研究 (2008)
  • Author(s): 荒井緑
  • Organizer: 神経組織の成長・再生・移植研究会第23回学術集会要旨集
  • Place of Presentation: 千葉
  • Year and Date: 20080000
• [Presentation] タンデム反応を用いるフラボノイド誘導体の合成と天然物探索のためのprotein-または cell-based assay の構築 (2008)
  • Author(s): 荒井緑
  • Organizer: 日本薬学会第128年会シンポジウム講演要旨集
  • Place of Presentation: 横浜
  • Year and Date: 20080000
• [Presentation] Synthesis of small molecules based on natural products targeting signaling pathways (2007)
  • Author(s): M. A. Arai, M. Ishibashi
  • Organizer: The 2007 International Symposium on Catalysis and Fine Chemicals (C&FC2007)
  • Place of Presentation: Singapore
  • Year and Date: 20071216-20071221
• [Presentation] Search for bioactive natural products targeting signaling molecules in cancer-related biological pathways (2007)
  • Author(s): M. Ishibashi
  • Organizer: The 6^<th> Princess Chulabhorn International Science Congress (PC VI)
  • Place of Presentation: Bangkok, Thailand
  • Year and Date: 20071125-20071129
• [Presentation] Search for Unexplored Natural Products Targeting Signaling Molecules (2007)
  • Author(s): M. Ishibashi
  • Organizer: 2nd International Conference on Cutting-Edge Organic Chemistry in Asia
  • Place of Presentation: Pusan, Korea
  • Year and Date: 20070902-20070906
• [Presentation] Listen to natural products : Synthesis and biological evaluation of flavonoid-framework (2007)
  • Author(s): M. A. Arai
  • Organizer: 2nd International Conference on Cutting-Edge Organic Chemistry in Asia
  • Place of Presentation: Pusan, Korea
  • Year and Date: 20070902-20070906
• [Presentation] Studies on death receptor 5 inducing natural products of tropical medicinal plants (2007)
  • Author(s): T. Ohtsuki, H. Kikuchi, T. Sakai, M. Ishibashi
  • Organizer: 第66回日本癌学会学術総会要旨集
  • Year and Date: 20070000
• [Presentation] ヘッジホッグシグナル伝達経路を阻害する天然物の探索 (2007)
  • Author(s): 細谷孝博, 荒井緑, 舘野史, 小谷野喬, T. Kowithayakorn, 石橋正己
  • Organizer: 第49回天然有機化合物討論会講演要旨集
  • Year and Date: 20070000
• [Presentation] 真性粘菌からの生理活性物質の探索 (2007)
  • Author(s): 石橋正己
  • Organizer: 第25回日本植物細胞分子生物学会千葉大会シンポジウム講演要旨集
  • Year and Date: 20070000
• [Book] ソレル有機化学(上) (2009)
  • Author(s): 村田道雄, 石橋正己, 木越英夫, 佐々木誠, 監訳 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, 共訳
  • Publisher: 東京化学同人
• [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, 監訳 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, 共訳
  • Publisher: 東京化学同人
• [Book] 抗菌, 抗かび活性物質(天然物化学―海洋生物編, 山村庄介・長谷川宏司・木越英夫編) (2008)
  • Author(s): 石橋正己
  • Total Pages: 182-190
  • Publisher: アイピーシー
• [Book] 脂肪酸とポリケタイド, パートナー天然物化学(海老塚豊・森田博史編) (2007)
  • Author(s): 石橋正己
  • Total Pages: 62-95
  • Publisher: 南江堂
• [Remarks] ホームページ等
  • URL: http://www.p.chiba-u.ac.jp/lab/kouzou/index.html
• [Patent(Industrial Property Rights)] ツビフェラールAおよびツビフェラールB (2010)
  • Inventor(s): 石橋正己・鎌田和明
  • Industrial Property Rights Holder: 千葉大学
  • Industrial Property Number: 特許第4465466号
  • Acquisition Date: 2010-03-05
• [Patent(Industrial Property Rights)] エリスロフレシンA, B, C及びD (2009)
  • Inventor(s): 石橋正己・宮川高・大槻崇・小谷野喬
  • Industrial Property Rights Holder: 千葉大学
  • Industrial Property Number: 特許特願2009-108489
  • Filing Date: 2009-04-27
• [Patent(Industrial Property Rights)] パルビフロレンHおよびパルビフロレンI (2009)
  • Inventor(s): 石橋正己・當銘一文・小谷野喬
  • Industrial Property Rights Holder: 千葉大学
  • Industrial Property Number: 特許第4359683号
  • Acquisition Date: 2009-08-21
• [Patent(Industrial Property Rights)] フザニンA, B, C及びD (2008)
  • Inventor(s): 石橋正己・会田渉・大槻崇
  • Industrial Property Rights Holder: 千葉大学
  • Industrial Property Number: 特許特願2008-088760
  • Filing Date: 2008-03-28
• [Patent(Industrial Property Rights)] エレウテリノシドA, B, C (2008)
  • Inventor(s): 石橋正己・李暁帆・大槻崇・小谷野喬
  • Industrial Property Rights Holder: 千葉大学
  • Industrial Property Number: 特許特願2008-20163
  • Filing Date: 2008-01-31
• [Patent(Industrial Property Rights)] フラボノイドの製造方法 (2007)
  • Inventor(s): 荒井緑・佐藤未奈・石橋正己
  • Industrial Property Rights Holder: 千葉大学
  • Industrial Property Number: 特許特願2007-224850
  • Filing Date: 2007-08-30