WEKO3
アイテム
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Identification of 3,4-Dihydro-2H,6H-pyrimido[1,2-c][1,3]benzothiazin-6-imine Derivatives as Novel Selective Inhibitors of Plasmodium falciparum Dihydroorotate Dehydrogenase
http://hdl.handle.net/10069/00041253
http://hdl.handle.net/10069/00041253dd53d4b6-ed00-4bac-ba20-8b6345071ee4
名前 / ファイル | ライセンス | アクション |
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ISYK1370_Hartuti.pdf (1.5 MB)
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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公開日 | 2022-02-10 | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | Identification of 3,4-Dihydro-2H,6H-pyrimido[1,2-c][1,3]benzothiazin-6-imine Derivatives as Novel Selective Inhibitors of Plasmodium falciparum Dihydroorotate Dehydrogenase | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Plasmodium falciparum | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | dihydroorotate dehydrogenase | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | inhibitor screening | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | ubiquinone | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | antimalarial drug | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||
資源タイプ | doctoral thesis | |||||
アクセス権 | ||||||
アクセス権 | open access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
著者 |
Hartuti, Endah Dwi
× Hartuti, Endah Dwi |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Plasmodium falciparum’s resistance to available antimalarial drugs highlights the need for the development of novel drugs. Pyrimidine de novo biosynthesis is a validated drug target for the prevention and treatment of malaria infection. P. falciparum dihydroorotate dehydrogenase (PfDHODH) catalyzes the oxidation of dihydroorotate to orotate and utilize ubiquinone as an electron acceptor in the fourth step of pyrimidine de novo biosynthesis. PfDHODH is targeted by the inhibitor DSM265, which binds to a hydrophobic pocket located at the N-terminus where ubiquinone binds, which is known to be structurally divergent from the mammalian orthologue. In this study, we screened 40,400 compounds from the Kyoto University chemical library against recombinant PfDHODH. These studies led to the identification of 3,4-dihydro-2H,6H-pyrimido[1,2-c][1,3]benzothiazin-6-imine and its derivatives as a new class of PfDHODH inhibitor. Moreover, the hit compounds identified in this study are selective for PfDHODH without inhibition of the human enzymes. Finally, this new scaffold of PfDHODH inhibitors showed growth inhibition activity against P. falciparum 3D7 with low toxicity to three human cell lines, providing a new starting point for antimalarial drug development. | |||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 長崎大学学位論文 学位記番号:博(医歯薬)甲第1370号 学位授与年月日:令和3年9月17日 | |||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Author: Endah Dwi Hartuti, Takaya Sakura, Mohammed S. O. Tagod, Eri Yoshida, Xinying Wang, Kota Mochizuki, Rajib Acharjee, Yuichi Matsuo, Fuyuki Tokumasu, Mihoko Mori, Danang Waluyo, Kazuro Shiomi, Tomoyoshi Nozaki, Shinjiro Hamano, Tomoo Shiba, Kiyoshi Kita and Daniel Ken Inaoka | |||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Citation: International Journal of Molecular Sciences, 22(13), art. no. 7236; 2021 | |||||
書誌情報 |
International Journal of Molecular Sciences 巻 22, 号 13, p. 7236, 発行日 2021-09-17 |
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EISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 1422-0067 | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | 10.3390/ijms22137236 | |||||
権利 | ||||||
権利情報 | © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). | |||||
著者版フラグ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
その他のタイトル | ||||||
その他のタイトル | 熱帯熱マラリア原虫ジヒドロオロト酸脱水素酵素の新規選択的阻害剤の同定 | |||||
出版者 | ||||||
出版者 | MDPI | |||||
関係URI | ||||||
識別子タイプ | HDL | |||||
関連識別子 | http://hdl.handle.net/10069/00040957 | |||||
学位名 | ||||||
学位名 | 博士(医学) | |||||
学位授与機関 | ||||||
学位授与機関識別子Scheme | kakenhi | |||||
学位授与機関識別子 | 17301 | |||||
学位授与機関名 | Nagasaki University (長崎大学) | |||||
学位授与年月日 | ||||||
学位授与年月日 | 2021-09-17 | |||||
学位授与番号 | ||||||
学位授与番号 | 甲医歯薬第1370号 | |||||
学位の種類 | ||||||
課程博士 | ||||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Nagasaki University (長崎大学), 博士(医学) (2021-09-17) |