並列タイトル等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
タイトル（掲載誌）Antimicrobial Agents and Chemotherapy
授与機関名Nagasaki University (長崎大学)
一般注記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.
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
Author: Keith Kiplangat Talaam, Daniel Ken Inaoka, Takeshi Hatta, Daigo Tsubokawa, Naotoshi Tsuji, Minoru Wada, Hiroyuki Saimoto, Kiyoshi Kita, Shinjiro Hamano
Citation: Antimicrobial Agents and Chemotherapy, 65(10), art. no. e00418-21; 2021
identifier:Nagasaki University (長崎大学), 博士(医学) (2021-12-01)
http://hdl.handle.net/10069/00041147
DOIinfo:doi/10.1128/AAC.00418-21
コレクション（個別）国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文
受理日（W3CDTF）2022-06-05T18:01:14+09:00
連携機関・データベース国立国会図書館 : 国立国会図書館デジタルコレクション