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Development of antimalarial drug targeting plasmodium falciparum dynamin

Research Project

Project/Area Number 23659213
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Parasitology (including Sanitary zoology)
Research InstitutionOkayama University

Principal Investigator

TAKEI Kohji  岡山大学, 医歯(薬)学総合研究科, 教授 (40322226)

Co-Investigator(Kenkyū-buntansha) YAMADA Hiroshi  岡山大学, 大学院・医歯薬学総合研究科, 准教 (80325092)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsマラリア / アクチン / ダイナミン / コルタクチン / 阻害剤 / 感染症
Research Abstract

By in vitro actin polymerization assay, we identified N'-(4-(diethylamino) benzylidene)-4-methoxybenzohydrazide (DBHA) as a dynamin inhibitor. Effects of DBHA on ruffle formation and cell migration were also examined, and the results on DBHA were published in a journal article.
Dynamin isoforms present in plasmodium falciparum, pfDyn1 and pfDyn2, were expressed in insect cells, and they were purified. Using these recombinant proteins, we demonstrated that both pfDyn1 and pfDyn2 have GTPase activity. It was also shown that pfDyn1 and pfDyn2 have an ability to deform lipid membranes. Furthermore, pfDyn2 inhibitor candidate molecules were determined by GTPase activity assay-based drug screening.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (44 results)

All 2014 2013 2012 2011 Other

All Journal Article (15 results) (of which Peer Reviewed: 15 results) Presentation (24 results) Book (1 results) Patent(Industrial Property Rights) (4 results)

  • [Journal Article] N'-[4-(dipropylamino)benzylidene]-2-hydroxybenzohydrazide is a dynamin GTPase inhibitor that suppresses cancer cell migration and invasion by inhibiting actin polymerization2013

    • Author(s)
      Yamada, H., Abe, T., Li, S.A., Tago, S., Huang, P., Watanabe, M., Ikeda, S., Ogo, N., Asai, A., Takei, K
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 443 Issue: 2 Pages: 511-517

    • DOI

      10.1016/j.bbrc.2013.11.118

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Stabilization of actin bundles by a Dynamin 12013

    • Author(s)
      Yamada H, Abe T
    • Journal Title

      Cortactin ring complex is necessary for growth cone filopodia.

      Volume: 33 Issue: 10 Pages: 4514-4526

    • DOI

      10.1523/jneurosci.2762-12.2013

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] REIC/Dkk-3-encoding adenoviral vector as a potentially effective therapeutic agent for bladder cancer.2012

    • Author(s)
      Hirata et al.
    • Journal Title

      Int J Oncol.

      Volume: 41 Issue: 2 Pages: 559-564

    • DOI

      10.3892/ijo.2012.1503

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] A novel gene expression system for detecting viable bladder cancer cells2012

    • Author(s)
      Ueki, H., Watanabe, M., Kaku, H., Huang, P., Li, S.A., Ochiai, K., Hirata, T., Noguchi, H., Yamada, H., Takei, K., Nasu, Y, Kashiwakura Y, and Kumon H
    • Journal Title

      Int J Oncol

      Volume: 41 Pages: 135-140

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] The clathrin assembly protein PICALM is required for erythroid maturation and transferrin internalization in mice.2012

    • Author(s)
      鈴木 麻衣
    • Journal Title

      PLoS ONE

      Volume: 7 Issue: 2 Pages: 31854-31854

    • DOI

      10.1371/journal.pone.0031854

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] A novel gene expression system for detecting viable bladder cancer cells2012

    • Author(s)
      Hideo Ueki, et al
    • Journal Title

      International journal of oncology

      Volume: 41 Pages: 135-140

    • DOI

      10.3892/ijo.2012.1417

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] The clathrin assembly protein PICALM is required for erythroid maturation and transferrin internalization in mice.2012

    • Author(s)
      Suzuki, M.
    • Journal Title

      PLoS One

      Volume: 7

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Receptor Sorting within Endosomal Trafficking Pathway Is Facilitated by Dynamic Actin Filaments2011

    • Author(s)
      Emiko Ohashi, Kenji Tanabe, Yuji Henmi, Kumi Mesaki, Yuka Kobayashi, Kohji Takei
    • Journal Title

      PLoS ONE

      Volume: 6 Issue: 5 Pages: e19942-e19942

    • DOI

      10.1371/journal.pone.0019942

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Fission of tubular endosomes triggers endosomal acidification and movement2011

    • Author(s)
      Kumi Mesaki, Kenji Tanabe, Masanori Obayashi, Natsuko Oe, Kohji Takei
    • Journal Title

      PLoS ONE

      Volume: 6 Issue: 5 Pages: e19764-e19764

    • DOI

      10.1371/journal.pone.0019764

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Dynamin 2 associates with microtubules at mitosis and regulates cell cycle progression2011

    • Author(s)
      Ishida, N., Nakamura, Y., Tanabe, K., Li, S.A., and Takei, K
    • Journal Title

      Cell Struct Funct

      Volume: 36 Pages: 145-154

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Disruption of microtubule network rescues aberrant actin comets in dynamin2-depleted cells2011

    • Author(s)
      Yuji Henmi, Kenji Tanabe, Kohji Takei
    • Journal Title

      PLoS ONE

      Volume: 6 Issue: 12 Pages: e28603-e28603

    • DOI

      10.1371/journal.pone.0028603

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Disruption of microtubule network rescues aberrant actin comets in dynamin2-depleted cells.2011

    • Author(s)
      Henmi, Y.
    • Journal Title

      PLoS One

      Volume: 6

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Receptor sorting within endosomal trafficking pathway is facilitated by dynamic actin filaments.2011

    • Author(s)
      Ohashi, E.
    • Journal Title

      PLoS One

      Volume: 6

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Receptor sorting within endosomal trafficking pathway is facilitated by dynamic actin filaments.2011

    • Author(s)
      Mesaki, K.
    • Journal Title

      PLoS One

      Volume: 6

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Dynamin 2 associates with microtubules at mitosis and regulates cell cycle progression.2011

    • Author(s)
      Ishida, N.
    • Journal Title

      PLoS One

      Volume: 36 Pages: 145-154

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] 熱帯熱マラリア原虫ダイナミンGTPase の膜動態制御2014

    • Author(s)
      竹居孝二
    • Organizer
      第83回日本寄生虫学会大会
    • Place of Presentation
      愛媛大学
    • Related Report
      2013 Final Research Report
  • [Presentation] 熱帯熱マラリア原虫ダイナミンGTPaseの膜動態制御2014

    • Author(s)
      山田浩司、多湖翔太、高柳昌芳、阿部匡史、坪井敬文、金惠淑、竹居孝二
    • Organizer
      第83回日本寄生虫学会大会
    • Place of Presentation
      愛媛大学
    • Related Report
      2013 Annual Research Report
  • [Presentation] 熱帯熱マラリア原虫ダイナミンGTPase の膜動態制御と構造機能相関, 「ライフサイエンスの革新を目指した構造生命科学と先端的基盤技術」2013

    • Author(s)
      山田浩司
    • Organizer
      研究領域CREST/さきがけ合同キックオフミーティング及び研究成果報告会
    • Place of Presentation
      滋賀県守山市ラフォーレ琵琶湖
    • Related Report
      2013 Final Research Report
  • [Presentation] ダイナミンGTP アーゼは生体膜とアクチン細胞骨格をメカニカルに制御する, 「ライフサイエンスの革新を目指した構造生命科学と先端的基盤技術」2013

    • Author(s)
      竹居孝二
    • Organizer
      研究領域CREST/さきがけ合同キックオフミーティング及び研究成果報告会
    • Place of Presentation
      滋賀県守山市ラフォーレ琵琶湖
    • Related Report
      2013 Final Research Report
  • [Presentation] N'-(4-(dipropylamino)benzylidene)-2- hydroxybenzohydrazide is a dynamin GTPase inhibitor and suppresses cancer cell migration and invasion by inhibiting actin polymerization2013

    • Author(s)
      阿部匡史
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜市, パシフィコ横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] A novel mechanism of actin bundle formation supporting the formation of filopodia2013

    • Author(s)
      竹居孝二
    • Organizer
      第65回日本細胞生物学会大会
    • Place of Presentation
      名古屋市ウインクあいち
    • Related Report
      2013 Final Research Report
  • [Presentation] Mechanochemical regulation of actin dynamics by a Dynamin 1 / Cortactin ring complex2013

    • Author(s)
      山田浩司
    • Organizer
      第5回日本生物物理学会中国四国支部大会
    • Place of Presentation
      香川県直島ベネッセハウス
    • Related Report
      2013 Final Research Report
  • [Presentation] フィロポディア形成を担う新規アクチン線維束化機構2013

    • Author(s)
      竹居孝二、山田浩司、阿部匡史
    • Organizer
      第65回日本細胞生物学会大会
    • Place of Presentation
      ウインクあいち(愛媛県産業労働センター)
    • Related Report
      2013 Annual Research Report
  • [Presentation] N'-[4-(diethylamino)benzylidene]-4-methoxybenzohydrazide is a dynamin GTPase inhibitor and suppresses cancer cell migration and invasion by inhibiting actin polymerization.2013

    • Author(s)
      阿部匡史、渡部昌美、池田敏、小郷尚久、浅井章良、竹居孝二、山田浩司
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] ダイナミン2 は微小管を介してアクチンコメットを制御する2012

    • Author(s)
      逸見祐次
    • Organizer
      第53回日本生化学会中国・四国支部例会
    • Place of Presentation
      岡山大学
    • Year and Date
      2012-05-18
    • Related Report
      2013 Final Research Report
  • [Presentation] ホスファチジルイノシトール-4-キナーゼ IIα は初期エンドソームにおける選別 輸送を制御する2012

    • Author(s)
      田邊賢司
    • Organizer
      第53回日本生化学会中国・四国支部例会
    • Place of Presentation
      岡山大学
    • Year and Date
      2012-05-18
    • Related Report
      2013 Final Research Report
  • [Presentation] Dynamin GTPase / Cortactin ring complex is a mechanical devise stabilizing actin bundles2012

    • Author(s)
      竹居孝二
    • Organizer
      第38回生体エネルギー研究会
    • Place of Presentation
      岡山大学
    • Related Report
      2013 Final Research Report
  • [Presentation] Dynamin を標的にした抗がん剤の開発2012

    • Author(s)
      岡崎奈奈
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡国際会議場マリンメッセ福岡
    • Related Report
      2013 Final Research Report
  • [Presentation] Phosphorylation of cortactin by PKC is a key factor for filopodia formation of growth cones2012

    • Author(s)
      山田浩司
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡国際会議場マリンメッセ福岡
    • Related Report
      2013 Final Research Report
  • [Presentation] PKC phosphorylation of cortactin is implicated in the regulation of actin dynamics2011

    • Author(s)
      竹居孝二
    • Organizer
      第51回米国細胞生物学会
    • Place of Presentation
      米国デンバー
    • Related Report
      2013 Final Research Report
  • [Presentation] ダイナミン・コルタクチン複合体によるアクチン細胞骨格制御機構2011

    • Author(s)
      竹居孝二
    • Organizer
      第33回生体膜と薬物の相互作用シンポジウム
    • Place of Presentation
      岡山大学
    • Related Report
      2013 Final Research Report
  • [Presentation] Phosphorylation of Cortactin by PKC alpha is involved in formation of filopodia of growth cones2011

    • Author(s)
      山田浩司
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      国立京都国際会館
    • Related Report
      2013 Final Research Report
  • [Presentation] Receptor Sorting Within Endosomal Trafficking Pathway Is Facilitated By Dynamic Actin Filaments2011

    • Author(s)
      逸見祐次
    • Organizer
      第63回日本細胞生物学会大会
    • Place of Presentation
      北海道大学
    • Related Report
      2013 Final Research Report
  • [Presentation] Phosphatidylinositol 4-kinase II alpha is required for receptor sorting at early endosomes2011

    • Author(s)
      田邊賢司
    • Organizer
      第63回日本細胞生物学会大会
    • Related Report
      2013 Final Research Report
  • [Presentation] Phosphorylation of cortactin by PKC is a key factor for filopodia formation of growth cone

    • Author(s)
      山田 浩司
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡国際会議場・マリンメッセ福岡(福岡)
    • Related Report
      2012 Research-status Report
  • [Presentation] Dynaminを標的にした抗遊走、浸潤薬の開発

    • Author(s)
      岡﨑 奈奈
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡国際会議場・マリンメッセ福岡(福岡)
    • Related Report
      2012 Research-status Report
  • [Presentation] Dynamin GTPase / Cortactin ring complex is a mechanochemical device stabilizing actin bundles

    • Author(s)
      竹居 孝二
    • Organizer
      日本生体エネルギー研究会 第38回討論会
    • Place of Presentation
      岡山大学薬学部(岡山)
    • Related Report
      2012 Research-status Report
  • [Presentation] ダイナミン・コルタクチン複合体によるアクチン細胞骨格制御機構

    • Author(s)
      竹居孝二
    • Organizer
      第33回生体膜と薬物の相互作用シンポジウム
    • Place of Presentation
      岡山市、岡山大学創立五十周年記念館
    • Related Report
      2011 Research-status Report
  • [Presentation] PKC phosphorylation of cortactin is implicated in the regulation of actin dynamics

    • Author(s)
      竹居孝二
    • Organizer
      第51回米国細胞生物学会
    • Place of Presentation
      米国、デンバー
    • Related Report
      2011 Research-status Report
  • [Book] Etiological role of dynamin in Charcot-Marie-Tooth disease. "Peripheral Neuropathy - Advances in Diagnostic and Therapeutic Approaches"2012

    • Author(s)
      Takei, K. and Tanabe, K
    • Publisher
      InTech (Rijeka, Croatia)
    • Related Report
      2013 Final Research Report
  • [Patent(Industrial Property Rights)] 抗浸潤薬の新規スクリーニング法および抗浸潤剤2012

    • Inventor(s)
      山田浩司, 竹居孝二, 道上宏之, 松井秀樹, 浅井章良
    • Industrial Property Rights Holder
      山田浩司, 竹居孝二, 道上宏之, 松井秀樹, 浅井章良
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2012-137489
    • Filing Date
      2012-06-19
    • Related Report
      2013 Final Research Report
  • [Patent(Industrial Property Rights)] フルボキサミンを配合することを特徴とする分子標的型抗癌剤(特に抗脳腫瘍治療薬剤:第二医薬品用途)2012

    • Inventor(s)
      道上宏之, 林圭一郎, 松井秀樹, 山田浩司, 竹居孝二, 宮地弘幸, 浅井章良
    • Industrial Property Rights Holder
      道上宏之, 林圭一郎, 松井秀樹, 山田浩司, 竹居孝二, 宮地弘幸, 浅井章良
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2012-263317
    • Filing Date
      2012-11-30
    • Related Report
      2013 Final Research Report
  • [Patent(Industrial Property Rights)] 抗浸潤薬の新規スクリーニング法および抗浸潤剤2012

    • Inventor(s)
      山田浩司、竹居 孝二、道上宏之、 松井秀樹、浅井 章良
    • Industrial Property Rights Holder
      山田浩司、竹居 孝二、道上宏之、 松井秀樹、浅井 章良
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2012-137489
    • Filing Date
      2012-06-19
    • Related Report
      2012 Research-status Report
  • [Patent(Industrial Property Rights)] フルボキサミンを配合することを特徴とする分子標 的型抗癌剤(特に抗脳腫瘍治療薬剤:第二医薬品 用途)2012

    • Inventor(s)
      道上宏之 他6名
    • Industrial Property Rights Holder
      道上宏之 他6名
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2012-263317
    • Filing Date
      2012-11-30
    • Related Report
      2012 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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