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Mitochondria as a Potential Target for the Development of Prophylactic and Therapeutic Drugs against Schistosoma mansoni Infection
http://hdl.handle.net/10069/00041551
http://hdl.handle.net/10069/00041551abc229bb-5c33-44fe-8980-aea4680a1dfd
名前 / ファイル | ライセンス | アクション |
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ISYK1386_Talaam.pdf (1.6 MB)
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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公開日 | 2022-05-24 | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | Mitochondria as a Potential Target for the Development of Prophylactic and Therapeutic Drugs against Schistosoma mansoni Infection | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | schistosomiasis | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | mitochondria | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | electron transport chain | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | fumarate respiration | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | in vivo model | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | drug development | |||||
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 |
Talaam, Keith Kiplangat
× Talaam, Keith Kiplangat |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | The emergence of parasites resistant to praziquantel, the only therapeutic agent, and its ineffectiveness as a prophylactic agent (inactive against the migratory/juvenile Schistosoma mansoni), make the development of new antischistosomal drugs urgent. The parasite’s mitochondrion is an attractive target for drug development, because this organelle is essential for survival throughout the parasite’s life cycle. We investigated the effects of 116 compounds against Schistosoma mansoni cercaria motility that have been reported to affect mitochondrion-related processes in other organisms. Next, eight compounds plus two controls (mefloquine and praziquantel) were selected and assayed against the motility of schistosomula (in vitro) and adults (ex vivo). Prophylactic and therapeutic assays were performed using infected mouse models. Inhibition of oxygen consumption rate (OCR) was assayed using Seahorse XFe24 analyzer. All selected compounds showed excellent prophylactic activity, reducing the worm burden in the lungs to less than 15% of that obtained in the vehicle control. Notably, ascofuranone showed the highest activity, with a 98% reduction of the worm burden, suggesting the potential for the development of ascofuranone as a prophylactic agent. The worm burden of infected mice with S. mansoni at the adult stage was reduced by more than 50% in mice treated with mefloquine, nitazoxanide, amiodarone, ascofuranone, pyrvinium pamoate, or plumbagin. Moreover, adult mitochondrial OCR was severely inhibited by ascofuranone, atovaquone, and nitazoxanide, while pyrvinium pamoate inhibited both mitochondrial and nonmitochondrial OCRs. These results demonstrate that the mitochondria of S. mansoni are a feasible target for 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1386号 学位授与年月日:令和3年12月1日 | |||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Author: Keith Kiplangat Talaam, Daniel Ken Inaoka, Takeshi Hatta, Daigo Tsubokawa, Naotoshi Tsuji, Minoru Wada, Hiroyuki Saimoto, Kiyoshi Kita, Shinjiro Hamano |
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内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Citation: Antimicrobial Agents and Chemotherapy, 65(10), art. no. e00418-21; 2021 | |||||
書誌情報 |
Antimicrobial Agents and Chemotherapy 巻 65, 号 10, p. e00418-21, 発行日 2021-12-01 |
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ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 0066-4804 | |||||
EISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 1098-6596 | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1128/AAC.00418-21 | |||||
権利 | ||||||
権利情報 | © 2021 American Society for Microbiology. All Rights Reserved. | |||||
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 | マンソン住血吸虫のミトコンドリアは予防と治療効果が期待できる創薬標的である | |||||
出版者 | ||||||
出版者 | American Society for Microbiology | |||||
関係URI | ||||||
識別子タイプ | HDL | |||||
関連識別子 | http://hdl.handle.net/10069/00041147 | |||||
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 | 2021-12-01 | |||||
学位授与番号 | ||||||
学位授与番号 | 甲医歯薬第1386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) (2021-12-01) |