Discovery of antitumor drug candidates from rainforest plants

• Project/Area Number: 25293024
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Natural medicines
• Research Institution: Kanazawa University
• Principal Investigator: Goto Kyoko 金沢大学, 薬学系, 准教授 (50180245)
• Co-Investigator(Kenkyū-buntansha): 三宅 克典 東京薬科大学, 薬学部, 助教 (20597687)
• Research Collaborator: GOTO Masuo Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Research Professor
• Project Period (FY): 2013-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000); Fiscal Year 2016: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2015: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2014: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
• Keywords: 熱帯雨林産植物 / 熱帯林産植物 / 抗がん剤リード / 熱帯林植物 / 抗がん剤候補 / 生理活性天然物 / 発がん予防効果 / 熱帯林植物産天然物

Outline of Final Research Achievements

Over 60 of novel natural products were isolated from six rainforest plant extracts, which were provided by National Cancer Institute in USA. Among them, the potent antitumor compounds were selected and constructed their total synthetic routes. Further preparations of their derivatives and study of structure-activity relationship were carried out.

Research Products

• [Int'l Joint Research] ノースカロライナ大学/国立がん研究所(米国)
• [Int'l Joint Research] アカデミアシニカ(台湾)
• [Int'l Joint Research] Academia Sinica(Taiwan)
• [Int'l Joint Research] National Cancer Institute/University of North Carolina(米国)
• [Int'l Joint Research] ノースカロライナ大学(米国)
• [Int'l Joint Research] アカデミアシニカ 中央研究院農業生物科技研究所(台湾)
• [Journal Article] Secondary Metabolites, Monoterpene?Polyketides Containing a Spiro[3.5]nonane from Cryptocarya laevigata (2018)
  • Author(s): Tsurumi Fumika、Miura Yuta、Saito Yohei、Miyake Katsunori、Fujie Tetsuo、Newman David J.、O’Keefe Barry R.、Lee Kuo-Hsiung、Nakagawa-Goto Kyoko
  • Journal Title: Organic Letters Volume: 20 Issue: 8 Pages: 2282-2286
  • DOI: 10.1021/acs.orglett.8b00624
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Total Synthesis of Antiproliferative Parvifloron F (2018)
  • Author(s): Saito Yohei、Goto Masuo、Nakagawa-Goto Kyoko
  • Journal Title: Organic Letters Volume: 20 Issue: 3 Pages: 628-631
  • DOI: 10.1021/acs.orglett.7b03763
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Corymbulosins I-W, Cytotoxic Clerodane Diterpenes from the Bark of Laetia corymbulosa (2018)
  • Author(s): Aimaiti Simayijiang、Suzuki Airi、Saito Yohei、Fukuyoshi Shuichi、Goto Masuo、Miyake Katsunori、Newman David J.、O’Keefe Barry R.、Lee Kuo-Hsiung、Nakagawa-Goto Kyoko
  • Journal Title: The Journal of Organic Chemistry Volume: 83 Issue: 2 Pages: 951-963
  • DOI: 10.1021/acs.joc.7b02951
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Phytoagent deoxyelephantopin derivative inhibits triple negative breast cancer cell activity by inducing oxidative stress-mediated paraptosis-like cell death (2017)
  • Author(s): Shiau Jeng-Yuan、Nakagawa-Goto Kyoko、Lee Kuo-Hsiung、Shyur Lie-Fen
  • Journal Title: Oncotarget Volume: 8 Issue: 34 Pages: 56942-56958
  • DOI: 10.18632/oncotarget.18183
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Antitubulin effects of aminobenzothiophene-substituted triethylated chromones (2017)
  • Author(s): Kobayashi Yukiko、Saito Yohei、Goto Masuo、Nakagawa-Goto Kyoko
  • Journal Title: Bioorganic & Medicinal Chemistry Letters Volume: 27 Issue: 12 Pages: 2731-2735
  • DOI: 10.1016/j.bmcl.2017.04.055
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Phytoagent Deoxyelephantopin and Its Derivative Inhibit Triple Negative Breast Cancer Cell Activity through ROS-Mediated Exosomal Activity and Protein Functions (2017)
  • Author(s): Shiau Jeng-Yuan、Chang Yong-Qun、Nakagawa-Goto Kyoko、Lee Kuo-Hsiung、Shyur Lie-Fen
  • Journal Title: Frontiers in Pharmacology Volume: 8 Pages: 1-15
  • DOI: 10.3389/fphar.2017.00398
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Corymbulosins D-H, 2-hydroxy- and 2-oxo-clerodane diterpenes from the bark of Laetia corymbulosa (2017)
  • Author(s): Suzuki A, Fukuyoshi S, Saito Y, Goto M, Miyake K, Newman DJ, O’Keefe BR, Lee KH, Nakagawa-Goto K
  • Journal Title: Journal of Natural Products Volume: ASAP Issue: 4 Pages: 1065-1072
  • DOI: 10.1021/acs.jnatprod.6b01151
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] (－)-Neocaryachine, An antiproliferative pavine alkaloid from Cryptocarya laevigata Induces DNA Double-strand Breaks (2017)
  • Author(s): Suzuki Y, Saito Y, Goto M, Newman DJ, O’Keefe BR, Lee KH, Nakagawa-Goto K
  • Journal Title: Journal of Natural Products Volume: 80 Issue: 1 Pages: 220-224
  • DOI: 10.1021/acs.jnatprod.6b01153
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A Novel Clerodane Diterpene from <i>Vitex cofassus</i> (2017)
  • Author(s): Rasyid FA, Fukuyoshi S, Ando H, Miyake K, Atsumi T, Fujie T, Saito Y, Goto M, Shinya T, Mikage M, Sasaki, Nakagawa-Gotoa K
  • Journal Title: Chemical and Pharmaceutical Bulletin Volume: 65 Issue: 1 Pages: 116-120
  • DOI: 10.1248/cpb.c16-00775
  • NAID: 130005187753
  • ISSN: 0009-2363, 1347-5223
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Phenylethylchromones with in vitro antitumor promoting activity from Aquilaria filarial (2017)
  • Author(s): Suzuki A, Miyake K, Saito Y, Faradiba, Tokuda H, Takeuchi M, Suzuki N, Ichiishi E, Fujie T, Goto M, Sasaki S, Nakagawa-Goto K
  • Journal Title: Planta Medica Volume: 83 Issue: 03/04 Pages: 300-305
  • DOI: 10.1055/s-0042-110858
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Total synthesis and in vitro anti tumor-promoting activity of racemic acetophenone monomers from Acronychia trifoliolata (2016)
  • Author(s): Morita C, Kobayashi Y, Tokuda H, Saito Y, Miyake M, Suzuki N, Ichiishi E, Lee KH, Nakagawa-Goto K
  • Journal Title: Journal of Natural Products Volume: 79 Issue: 11 Pages: 2890-2897
  • DOI: 10.1021/acs.jnatprod.6b00646
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Acetophenone monomers from Acronychia trifoliolata (2016)
  • Author(s): Miyake M, Suzuki A, Morita C, Goto M, Newman DJ, O’Keefe B, Morris-Natschke SL, Lee KH, Nakagawa-Goto K
  • Journal Title: Journal of Natural Products Volume: 79 Issue: 11 Pages: 2883-2889
  • DOI: 10.1021/acs.jnatprod.6b00645
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Triethylated chromones with substituted naphthalenes as novel tubulin inhibitors (2016)
  • Author(s): Nakagawa-Goto K, Taniguchi Y, Watanabe Y, Oda A, Ohkoshi E, Hamel E, Lee KH, Goto M
  • Journal Title: Bioorganic & Medicinal Chemistry Volume: 24 Pages: 6048-6057
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Novel sesquiterpene lactone analogues as potent anti-breast cancer agents (2016)
  • Author(s): Nakagawa-Goto K, Chen JY, Cheng YT, Lee WL, Takeya, M, Saito Y, Lee KH, Shyur LF
  • Journal Title: Molecular Oncology Volume: - Issue: 6 Pages: 921-937
  • DOI: 10.1016/j.molonc.2016.03.002
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A novel plant sesquiterpene lactone derivative DETD-35 suppresses BRAFV600E mutant melanoma growth and overcomes acquired vemurafenib resistance in mice (2016)
  • Author(s): Feng JH, Nakagawa-Goto K, Lee KH, Shyur LF
  • Journal Title: Molecular Cancer Therapeutics Volume: - Issue: 6 Pages: 1163-1176
  • DOI: 10.1158/1535-7163.mct-15-0973
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Development of a novel class of tubulin inhibitor from desmosdumotin B with a hydroxylated bicyclic B-ring (2015)
  • Author(s): Nakagawa-Goto K, Oda A, Hamel E, Ohkoshi E, Bastow KF, Lee KH, Goto M
  • Journal Title: J Med Chem Volume: 58 Issue: 5 Pages: 2378-2389
  • DOI: 10.1021/jm501859j
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 熱帯雨林植物ハスノハギリ科Hernandia peltataの成分研究 (2018)
  • Author(s): Simayijiang Aimaiti、斎藤洋平、後藤益生、David J. Newman、Barry R. O’Keefe、 Kuo-Hsiung Lee、後藤（中川）享子
  • Organizer: 日本薬学会第138年会
• [Presentation] Noreremophilane誘導体の合成とトリプルネガティブ乳がん細胞選択的増殖抑制効果 (2018)
  • Author(s): 佐賀野桃子、齋藤洋平、後藤益生、後藤（中川）享子
  • Organizer: 日本薬学会第138年会
• [Presentation] 新規ラクトン化合物Cryptolaevilactones AーCの合成と絶対立体構造の決定 (2018)
  • Author(s): 三浦悠太、齋藤洋平、後藤（中川）享子
  • Organizer: 日本薬学会第138年会
• [Presentation] 新規ラクトン化合物Cryptolaevilactone M の合成と絶対立体構造の決定 (2018)
  • Author(s): 中野美咲、齋藤洋平、後藤（中川）享子
  • Organizer: 日本薬学会第138年会
• [Presentation] ベンゾチオフェンフラボノイド誘導体のがん細胞増殖抑制効果と構造活性相関 (2018)
  • Author(s): 平澤幸香、谷口由花子、齋藤洋平、後藤益生、後藤（中川）享子
  • Organizer: 日本薬学会第138年会
• [Presentation] 去勢抵抗性前立腺がん克服を目指したカルコン誘導体の創出 (2018)
  • Author(s): 齋藤洋平、溝上敦、泉浩二、内藤伶奈人、後藤 益生、後藤（中川）享子
  • Organizer: 日本化学会第98春季年会
• [Presentation] 抗腫瘍活性を有するパビンアルカロイドの合成、構造活性相関研究ならびに作用機序の解明 (2017)
  • Author(s): 三浦悠太、鈴木結貴、斎藤洋平、後藤益生、後藤（中川）享子
  • Organizer: 日本薬学会第137年会
  • Place of Presentation: 仙台
  • Year and Date: 2017-03-27
• [Presentation] 去勢抵抗性前立腺がんに有効なフラボノイド誘導体の創出研究 (2017)
  • Author(s): 斎藤洋平、溝上 敦、泉 浩二、武澤 雄太、後藤益生、後藤（中川）享子
  • Organizer: 日本薬学会第137年会
  • Place of Presentation: 仙台
  • Year and Date: 2017-03-27
• [Presentation] ヤナギ科Laetia corymbulosaから単離された新規クレロダンジテルペン, corymbulosins D-Lと抗腫瘍活性 (2017)
  • Author(s): 鈴木愛理，SIMAYIJIANG AIMAITI、福吉修一、斎藤洋平、後藤益生、David J. Newman、Barry R. O’Keefe、 Kuo-Hsiung Lee、後藤（中川）享子
  • Organizer: 日本薬学会第137年会
  • Place of Presentation: 仙台
  • Year and Date: 2017-03-26
• [Presentation] 4-epi-Parvifloron類の合成と抗トリプルネガティブ乳がん選択性向上にむけての試み (2017)
  • Author(s): 宮島由衣、竹谷宗久、斎藤洋平、後藤益生、後藤（中川）享子
  • Organizer: 日本薬学会第137年会
  • Place of Presentation: 仙台
  • Year and Date: 2017-03-26
• [Presentation] 熱帯雨林植物の成分研究：Acronychia trifoliolata に含有されるアセトフェノンダイマー (2017)
  • Author(s): 三宅克典、鈴木愛理、後藤益生、David J. Newman、Gordon M. Cragg、Barry O’Keefe、Kuo-Hsiung Lee、後藤（中川）享子
  • Organizer: 日本薬学会第137年会
  • Place of Presentation: 仙台
  • Year and Date: 2017-03-26
• [Presentation] 生理活性ジテルペン、パルビフロロンFの全合成 (2017)
  • Author(s): 齋藤洋平、後藤益生、後藤（中川）享子
  • Organizer: 日本化学会第97春季年会
  • Place of Presentation: 東京
  • Year and Date: 2017-03-22
• [Presentation] 4-epi-Parvifloron類の合成と抗トリプルネガティブ乳がん選択性向上にむけての試み (2017)
  • Author(s): 宮島由衣、 竹谷宗久、 斎藤洋平、 後藤益生、 後藤（中川）享子
  • Organizer: 第15回次世代を担う若手のためのフィジカル・フォーラム
• [Presentation] Total Synthesis of Bioactive Diterpene, Parvifloron F (2017)
  • Author(s): Saito Y, Goto M, Nakagawa-Goto K
  • Organizer: 254th ACS National Meeting & Exposition
  • Int'l Joint Research
• [Presentation] 天然物基本骨格から細胞周期阻害剤の創成 (2017)
  • Author(s): 後藤（中川）享子
  • Organizer: 第129回薬学会北陸支部例会
  • Invited
• [Presentation] ズキ科Alangium longiforumから単離されたアルカロイド成分 (2016)
  • Author(s): 竹内美沙、斎藤洋平、後藤益生、David J. Newman、Gordon M. Cragg、Barry O’Keefe、Kuo-Hsiung Lee、後藤（中川）享子
  • Organizer: 日本生薬学会第63回年会
  • Place of Presentation: 富山
  • Year and Date: 2016-09-24
• [Presentation] Parvifloron類を含むアビエタン誘導体の抗腫瘍活性評価と構造活性相関 (2016)
  • Author(s): 宮島由衣、斎藤洋平、竹谷宗久、後藤益生、後藤（中川）享子
  • Organizer: 日本薬学会第136年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-03-27
• [Presentation] Acronychia trifoliolata含有のアセトフェノンモノマー体の合成 (2016)
  • Author(s): 森田千尋、小林佑希子、斎藤洋平、三宅克典、後藤（中川）享子
  • Organizer: 日本薬学会第136年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-03-27
• [Presentation] 熱帯雨林植物の成分研究 Acronychia trifoliolataに含有されるアセトフェノンモノマー (2016)
  • Author(s): 三宅克典、鈴木愛理、後藤益生、David J.Newman、Gordon M. Cragg、Barry O’Keefe、Kuo-Hsiung Lee、後藤（中川）享子
  • Organizer: 日本薬学会第136年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-03-27
• [Presentation] インドネシア産Agarwoodから単離された2-(2-Phenylethyl)chromone類と発がん抑制効果 (2016)
  • Author(s): 鈴木愛理，FARADIBA AbdulRasyid、三宅克典、斎藤洋平、徳田春邦、鈴木信孝、後藤益生、 佐々木陽平、後藤（中川）享子
  • Organizer: 日本薬学会第136年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-03-27
• [Presentation] A novel plant sesquiterpene lactone derivative DETD-35 suppresses BRAFV600E mutant melanoma growth and overcomes acquired vemurafenib resistance in mice (2015)
  • Author(s): Jia-Hua Feng, Kyoko Nakagawa-Goto, Kuo-Hsiung Lee, Lie-Fen Shyur
  • Organizer: AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics
  • Place of Presentation: アメリカ ボストン
  • Year and Date: 2015-11-05
  • Int'l Joint Research
• [Presentation] Parviflorone 類の全合成と triple negative 乳がんを標的とした抗腫瘍活性評価 (2015)
  • Author(s): 竹谷宗久、斎藤洋平、後藤益生、後藤（中川）享子
  • Organizer: 日本薬学会第１３５年会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-26 – 2015-03-28
• [Patent(Industrial Property Rights)] トリプルネガティブ乳がん選択的抗腫瘍活性を有するパルビフロロン誘導体 (2018)
  • Inventor(s): 後藤享子、斎藤洋平、宮島由衣
  • Industrial Property Rights Holder: 後藤享子、斎藤洋平、宮島由衣
  • Industrial Property Rights Type: 特許
  • Filing Date: 2018
• [Patent(Industrial Property Rights)] エピミノジベンゾアヌレン骨格を有する新規抗がん剤候補 (2016)
  • Inventor(s): 後藤享子、鈴木結貴、齋藤洋平
  • Industrial Property Rights Holder: 後藤享子、鈴木結貴、齋藤洋平
  • Industrial Property Rights Type: 特許
  • Filing Date: 2016-04-01
• [Patent(Industrial Property Rights)] Preparation of novel sesquiterpene derivatives and their use in inflammation and cancer treatment (2015)
  • Inventor(s): Lee KH, Nakagawa-Goto K, et al
  • Industrial Property Rights Holder: Lee KH, Nakagawa-Goto K, et al
  • Industrial Property Rights Type: 特許
  • Filing Date: 2015-12-10
  • Overseas
• [Patent(Industrial Property Rights)] Novel sesquiterpene derivatives and their use in inflammation or cancer treatment (2015)
  • Inventor(s): Shyur LF, Nakagawa-Goto K, et al
  • Industrial Property Rights Holder: Shyur LF, Nakagawa-Goto K, et al
  • Industrial Property Rights Type: 特許
  • Filing Date: 2015-05-06
  • Overseas