荒井 緑 (アライ ミドリ)

Arai, Midori

写真a

所属(所属キャンパス)

理工学部 生命情報学科 (矢上)

職名

教授

HP

経歴 【 表示 / 非表示

  • 2000年04月
    -
    2003年03月

    大阪大学産業科学研究所, 学術振興会特別研究員(PD)

  • 2001年01月
    -
    2002年03月

    Harvard University, 博士研究員

  • 2003年04月
    -
    2004年03月

    理化学研究所, 基礎科学特別研究員

  • 2004年04月
    -
    2006年03月

    帝京大学薬学部, 助教

  • 2006年04月
    -
    2008年03月

    千葉大学大学院薬学研究院, 助教授

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学歴 【 表示 / 非表示

  • 1991年04月
    -
    1995年03月

    東京大学, 薬学部, 製薬化学科

    大学, 卒業, その他

  • 1995年04月
    -
    1997年03月

    東京大学, 大学院薬学研究科

    大学院, 修了, 修士

  • 1997年04月
    -
    2000年03月

    東京大学, 大学院薬学研究科

    大学院, 修了, 博士

学位 【 表示 / 非表示

  • 博士(薬学), 東京大学, 課程, 2000年03月

免許・資格 【 表示 / 非表示

  • 薬剤師, 2000年06月

 

研究分野 【 表示 / 非表示

  • ライフサイエンス / 薬系化学、創薬科学 (天然物化学,ケミカルバイオロジー)

研究キーワード 【 表示 / 非表示

  • ケミカルバイオロジー

  • 天然物化学

研究テーマ 【 表示 / 非表示

  • 天然物ケミカルバイオロジー, 

    2020年04月
    -
    継続中

 

論文 【 表示 / 非表示

  • Identification of 1β,2α-epoxytagitinin C as a Notch inhibitor, oxidative stress mechanism and its anti-leukemia activity

    Makita Y., Saito S., Tsuchiya A., Ishibashi M., Arai M.A.

    Journal of Natural Medicines (Journal of Natural Medicines)  76 ( 1 ) 234 - 243 2022年01月

    ISSN  13403443

     概要を見る

    Notch signaling plays crucial roles in cell differentiation and proliferation, but aberrant activation of this signaling results in tumorigenesis and cancer progression. Notch signaling is thus a promising drug target for oncotherapy, and the development of Notch signaling inhibitors is eagerly awaited. Notch inhibitory activity-guided fractionation of a Spilanthes acmella extract led to the identification of five sesquiterpene lactones: tagitinin A (1), 1β,2α-epoxytagitinin C (2), tagitinin C (3), orizabin (4), and 2α-hydroxytirotundin (5). 1β,2α-Epoxytagitinin C (2) exhibited Notch signaling inhibition, with an IC50 of 25.6 μM, and was further evaluated for its activity against HPB-ALL, a Notch-activated leukemia cell line. Compound 2 showed potent cytotoxicity against HPB-ALL (IC50 1.7 μM) and arrested the cell cycle at the G2/M phase, but did not induce apoptotic cell death. Notch inhibitory mechanism analysis suggested that compound 2 transcriptionally suppresses Notch1 mRNA. In addition, we found that oxidative stress induction is critical for Notch signaling inhibition and the cytotoxicity of compound 2. This is the first mechanism of small molecule Notch inhibition. Our results demonstrate that 1β,2α-epoxytagitinin C (2) is a potential anti-leukemia agent and further investigation of this compound is warranted. Graphical abstract: [Figure not available: see fulltext.].

  • Evaluation of Naturally Occurring HIF-1 Inhibitors for Pulmonary Arterial Hypertension

    Arai M.A., Sakuraba K., Makita Y., Hara Y., Ishibashi M.

    ChemBioChem (ChemBioChem)  22 ( 18 ) 2799 - 2804 2021年09月

    ISSN  14394227

     概要を見る

    Pulmonary arterial hypertension (PAH) is a rare and severe progressive disorder characterized by high pulmonary artery pressure. Chronic hypoxia causes a metabolic disorder and the Warburg effect in pulmonary arterial smooth muscle cells (PASMCs). Pyruvate dehydrogenase kinase 1 (PDK1) is a key enzyme in Warburg effect increased by hypoxia-inducible factor (HIF-1). We constructed a cell-based luciferase assay system for HIF-1 inhibitors. Using this system, six HIF-1 inhibitors were identified. Among these inhibitors, the effect of tagitinin C (1) on PASMC was investigated. Tagitinin C (1) clearly decreased the amount of HIF-1β and the HIF-1 target PDK1. This result indicates that HIF-1 inhibitors effectively decrease PDK1 activity, which is a cause of the metabolic disorder and Warburg effect observed in PASMCs. Identifying naturally occurring HIF-1 inhibitors could provide novel insights into the development of PAH medications.

  • Target protein-oriented isolations for chemical biology based on natural products

    Arai M.A., Ishibashi M.

    Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry (Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry)  79 ( 7 ) 684 - 693 2021年07月

    ISSN  00379980

     概要を見る

    Natural products have contributed to development of medicine for a long time. The structures and bioactivities of natural products often exceed the human knowledge and imagination. We have developed target protein-oriented natural products isolation methods to quick find bioactive compounds from natural resources(compounds mixture). This review summarizes our recent results including protein beads methods and protein plate method for neural stem cells differentiation differentiation activators and and /or new showed cancer cytotoxicity drug candidates. against Isolated cancer compounds cells. Syntheses accelerated of isolated neural compounds stem cells were also described. As protein binding ability tightly related bioactivity, protein based natural products isolation would be a powerful way to find new candidate of medicines.

  • Target protein-oriented isolations for bioactive natural products

    Arai M.A.

    Chemical and Pharmaceutical Bulletin (Chemical and Pharmaceutical Bulletin)  69 ( 6 ) 503 - 515 2021年06月

    ISSN  00092363

     概要を見る

    Natural products are very attractive for development of medicine. Their structure and bioactivities are often beyond human knowledge and imagination. We have developed isolation methods for target protein-oriented natural products so as quickly to discover bioactive compounds from natural resources. This review summarizes our recent results including protein beads methods for neural stem cells differentiation activators and new cancer drug candidates. Syntheses of isolated compounds are described. We also developed protein plate method for identification of protein-protein interaction inhibitors. Because protein binding ability is tightly related to bioactivity, protein-based natural products isolation is a powerful means to find new candidate medicines.

  • Practical Stereoselective Synthesis of C3-Spirooxindole- and C2-Spiropseudoindoxyl-Pyrrolidines via Organocatalyzed Pictet-Spengler Reaction/Oxidative Rearrangement Sequence

    Kondo M., Matsuyama N., Aye T.Z., Mattan I., Sato T., Makita Y., Ishibashi M., Arai M.A., Takizawa S., Sasai H.

    Advanced Synthesis and Catalysis (Advanced Synthesis and Catalysis)  363 ( 10 ) 2648 - 2663 2021年05月

    ISSN  16154150

     概要を見る

    A stereoselective synthetic route to chiral C3-spirooxindole- and C2-spiropseudoindoxyl-pyrrolidines was accomplished by an enantioselective organocatalyzed Pictet-Spengler reaction of tryptamines and isotryptamines followed by a diastereoselective oxidative rearrangement using eco-friendly oxidants (i. e., NaOCl ⋅ 5H2O and Oxone®). This sequential reaction enables rapid access to chiral C3-spirooxindole- and C2-spiropseudoindoxyl-pyrrolidines in a one-pot process. A Wnt signaling inhibitory assay of the prepared enantioenriched spiro compounds demonstrated that they exhibited moderate activities. (Figure presented.).

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KOARA(リポジトリ)収録論文等 【 表示 / 非表示

総説・解説等 【 表示 / 非表示

  • Spirit of south countrywoman in research

    Arai M.A.

    Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry (Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry)  79 ( 1 ) 56 - 58 2021年01月

    ISSN  00379980

競争的研究費の研究課題 【 表示 / 非表示

  • 病原微生物の「浸潤進化」に学ぶ休眠遺伝子活性化と創薬シード分子の創製

    2021年04月
    -
    2024年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 荒井 緑, 基盤研究(B), 補助金,  研究代表者

 

担当授業科目 【 表示 / 非表示

  • 生命システム情報特別講義B

    2022年度

  • 生命情報特別講義第1

    2022年度

  • 生命情報輪講

    2022年度

  • 学外実習第3

    2022年度

  • 学外実習第2

    2022年度

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