Study of new broad spectrum of anti-parasitic agent and basis of molecular base of it

• Project/Area Number: 22390024
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Environmental pharmacy
• Research Institution: Okayama University
• Principal Investigator: WATAYA Yusuke 岡山大学, 大学院・医歯薬学総合研究科, 名誉教授 (90127598)
• Co-Investigator(Kenkyū-buntansha): SATO Akira 岡山大学, 大学院・医歯薬学総合研究科, 助教 (40530663) ; KIM Hye-sook 岡山大学, 大学院・医歯薬学総合研究科, 准教授 (70314664) ; DOI Hiroyuki 岡山大学, 大学院・医歯薬学総合研究科, 教授 (20452568)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2012: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2011: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2010: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
• Keywords: 住血吸虫 / マラリア / 分子生物学 / 抗寄生虫薬 / ゲノミクス / プロテオミクス / マンソン住血吸虫 / マラリア原虫 / 広範囲抗寄生虫薬 / シストソミューラ / N-89 / 標的分子

Research Abstract

The mechanism of action of N-89 for malaria and schistosomiasis;
(1) Total 11 of proteins were changed by N-89 in Schistosoma mansoniusing comprehensive proteomics. Among them, paramyosin was reduced to 30% of control after 24hr treatment with N-89. Malaria parasite and S. mansoniwere not similar target molecules in proteomics with N-89 in the study and it will be necessary to validate further the differences in both 2 pathogens.
(2) Body length of S. mansoni was shorted by N-89 administration and production of hemozoin also decreased in vivo experiment.
(3) Rhodamine-N-89 adducts will may act incorporated into the parasite body clearly.

Research Products

• [Journal Article] Applications of triphenylpyrylium salt-sensitized electron transfer photo-oxygenation reactions to the synthesis of benzo-fused 1,4-diaryl-2,3- dioxabicyclo[2.2.2]octanes as new antimalarial cyclic peroxides. (2013)
  • Author(s): Kamata, M., Hagiwara, J., Hokari,T., Suzuki,C., Fujino,R., Kobayashi,S., Kim,H.-S.and Wataya, Y
  • Journal Title: Research on Chemical Intermediate Volume: 39 Pages: 127-137
  • URL: http://link.springer.com/article/10.1007/s11164-012-0637-3
  • Peer Reviewed
• [Journal Article] Plasmodium falciparumendoplasmic reticulum-resident calcium binding protein is a possible target of synthetic antimalarial endoperoxides, N-89 and N-251. (2012)
  • Author(s): Morita, M., Sanai, H., Hiramoto, A., Sato, A., Hiraoka, O., Sakura, T., Kaneko, O., Masuyama, A., Nojima, M., Wataya, Y. and Kim, H.-S.
  • Journal Title: J Proteome Res. Volume: 11 Pages: 5704-5711
  • URL: http://pubs.acs.org/doi/pdf/10.1021/pr3005315
  • Peer Reviewed
• [Journal Article] Andirolides HeP from the flower of andiroba (Carapa guianensis, Meliaceae). (2012)
  • Author(s): Tanaka, Y., Sakamoto, A., Inoue, T., Yamada, T., Kikuchi, T., Kajimoto, T., Muraoka, O., Sato, A., Wataya, Y., Kim, H.-S, and Tanaka, R.
  • Journal Title: Tetrahedron Volume: 68 Pages: 3669-3677
  • URL: http://www.sciencedirect.com/science/article/pii/S0040402011019727
  • Peer Reviewed
• [Journal Article] Plasmodium falciparum endoplasmic reticulum-resident calcium binding protein is a possible target of synthetic antimalarial endoperoxides, N-89 and N-251 (2012)
  • Author(s): Morita M., Sanai H., Hiramoto A., Sato A., Hiraoka O., Sakura T., Kaneko O., Masuyama A., Nojima M., Wataya Y., Kim H.-S.
  • Journal Title: Journal of Proteome Research Volume: 11 Pages: 5704-5711
  • DOI: 10.1021/pr3005315
  • Peer Reviewed
• [Journal Article] Andirolides H-P from the flower of andiroba (Carapa guianensis, Meliaceae). (2012)
  • Author(s): Tanaka Y., Sakamoto A., Inoue T., Yamada T., Kikuchi T., Kajimoto T., Muraoka O., Sato A., Wataya Y., Kim H.-S., Tanaka R.
  • Journal Title: Tetrahedron Volume: 68 Pages: 3669-3677
  • DOI: 10.1016/j.tet.2011.12.076
  • Peer Reviewed
• [Journal Article] tetraoxaspiro [7.11]nonadec-4-yl)hexan- 1-ol (N-251) and its carboxylic acid derivatives (2011)
  • Author(s): Sato, A, Kawai, S., Hiramoto, A., Morita, M., Tanigawa, N., Nakase, Y., Komichi, Y., Matsumoto, M., Hiraoka, O., Hiramoto, K., Tokuhara, H., Masuyama, A., Nojima, M., Higaki, K., Hayatsu, H., Wataya,Y., Kim, H.-S.
  • Journal Title: Parasitol. Int Volume: 60 (4) Pages: 488-492
  • URL: http://www.sciencedirect.com/science/article/pii/S138357691100136X
  • Peer Reviewed
• [Journal Article] Antimalarial Activity of Endoperoxide Compound 6-(1,2,6,7- Tetraoxaspiro[7.11]nonadec-4-yl)hexan-1-ol. (2011)
  • Author(s): Sato, A., Hiramoto, A., Morita, M., Matsumoto, M., Komich, Y., Nakase, Y., Tanigawa, N., Hiraoka, O., Hiramoto, K., Hayatsu, H., Higaki, K., Kawai, S., Masuyama, A., Nojima, M., Wataya,Y., Kim, H.-S.
  • Journal Title: Parasitol. Int. Volume: 60 Pages: 270-273
  • URL: http://www.sciencedirect.com/science/article/pii/S1383576911000444
  • Peer Reviewed
• [Journal Article] Schistosomicidal and antifecundity effects of oral treatment of synthetic endoperoxide N-89. (2011)
  • Author(s): Taniguchi, T., Kumagai, T., Shimogawara, R., Ichinose, S., Hiramoto, A., Sato, A., Morita, M., Nojima, M., Kim, H.-S., Wataya, Y., Ohta, N.
  • Journal Title: arasitology International Volume: 60 Pages: 231-236
  • URL: http://www.sciencedirect.com/science/article/pii/S1383576911000225
  • Peer Reviewed
• [Journal Article] Antimalarial Activity of 6-(1,2,6,7-Tetraoxaspiro[7.11]nonadec-4-yl) hexan-1-ol (N-251) and Its Carboxylic Acid Derivatives (2011)
  • Author(s): Sato A., Kawai S., Hiramoto A., Morita M., Tanigawa N., Nakase Y., Komichi Y., Matsumoto M., Hiraoka O., Hiramoto K., Tokuhara H., Masuyama A., Nojima M., Higaki K., Hayatsu H., Wataya Y., Kim H.-S.
  • Journal Title: Parasitology International Volume: 60 Pages: 488-492
  • DOI: 10.1016/j.parint.2011.08.017
  • Peer Reviewed
• [Journal Article] Antimalarial Activity of Endoperoxide Compound 6-(1,2,6,7-Tetraoxaspiro[7.11]nonadec-4-yl)hexan-1-ol (2011)
  • Author(s): Sato A., Hiramoto A., Morita M., Matsumoto M., Komichi Y., Nakase Y., Tanigawa N., Hiraoka O., Hiramoto K., Hayatsu H., Higaki K., Kawai S., Masuyama A., Nojima M., Wataya Y., Kim H.-S.
  • Journal Title: Parasitology International Volume: 60 Pages: 270-273
  • DOI: 10.1016/j.parint.2011.04.001
  • Peer Reviewed
• [Journal Article] Schistosomicidal and antifecundity effects of oral treatment of synthetic endoperoxide N-89 (2011)
  • Author(s): Taniguchi T, Kumagai T, Shimogawara R, Ichinose S, Hiramoto A, Sato A, Morita M, Nojima M, Kim HS, Wataya Y, Ohta N
  • Journal Title: Parasitol Int Volume: 60 Pages: 231-236
  • DOI: 10.1016/j.parint.2011.02.007
  • Peer Reviewed
• [Journal Article] Schistosomicidal and antifecundity effects of oral treatment of synthetic endoperoxide N-89. (2011)
  • Author(s): Taniguchi T, Kumagai T, Shimogawara R, Ichinose S, Hiramoto A, Sato A, Morita M, Nojima M, Kim HS, Wataya Y, Ohta N.
  • Journal Title: Parasitol Int. Volume: (in press)
  • Peer Reviewed
• [Journal Article] Antimalarial activity of endoperoxide compound 6-(1,2,6,7-tetraoxaspiro [7.11]nonadec-4-yl)hexan-1-ol. (2011)
  • Author(s): Sato, A., Hiramoto, A., Morita, M., Matsumoto M., Komichi Y., Nakase, Y., Tanigawa N., Hiraoka, O., Hiramoto, K., Hayatsu, H., Higaki, K., Kawai, A., Masuyama, A., Nojima, M., Wataya, Y., Kim, H.-S.
  • Journal Title: Parasitol Int. Volume: (in press)
  • Peer Reviewed
• [Journal Article] Geranyl derivatices of isoquinoline alkaloids show increased biological activities. (2010)
  • Author(s): Nishiyama, Y., Iwasa, K., Okada, S., Takeuchi, S., Moriyasu, M., Kamigauchi, M., Koyama, J., Takeuchi, A., Tokuda, H., Kim, H.-S., Wataya, Y., Takeda, K., Liu, Y., Wu, P., Bastow, K., Akiyama, T. and Lee, K
  • Journal Title: Heterocycles Volume: 81 Pages: 1193-1229
  • URL: http://www.heterocycles.jp/newlibrary/downloads/PDF/21203/81/5
  • Peer Reviewed
• [Journal Article] Protein expression profiles of necrosis and apoptosis induced by 5-Fluoro-2´-deoxyuridine in mouse cancer cells. (2010)
  • Author(s): Sato, A., Hiramoto, A., Wataya, Y. and Kim, H.-S.
  • Journal Title: Journal of Proteome Research Volume: 9 Pages: 1329-2338
  • URL: http://pubs.acs.org/doi/abs/10.1021/pr9010537
  • Peer Reviewed
• [Journal Article] Selective accumulation of rhodacyanine in plasmodial mitochondria is related to the growth inhibition of malaria parasites (2010)
  • Author(s): Morisaki, D., Kim, H.-S., Inoue, H., Terauchi, H., Kuge, S., Naganuma, A., Wataya, Y., Tokuyama, H., Ihara, M. and Takasu, K
  • Journal Title: Chemical Science Volume: 1 Pages: 206-209
  • URL: http://pubs.rsc.org/en/content/articlepdf/2010/sc/c0sc00125b
  • Peer Reviewed
• [Presentation] 経皮吸収型抗マラリア薬の開発研究 (2013)
  • Author(s): 中村由香、片本 茜、佐藤 聡、檜垣和孝、綿矢有佑、金 惠淑
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 横浜、神奈川
• [Presentation] In vivoにおける抗マラリア活性評価システムの開発 (2013)
  • Author(s): 大里泰規、片本 茜、中村由香、佐藤 聡、金 惠淑
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 横浜、神奈川
• [Presentation] 難治性感染症治療薬の開発研究 (2013)
  • Author(s): 金 惠淑、佐藤 聡、森田将之、綿矢有佑、熊谷 貴、下河原理江子、太田伸生
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 横浜、神奈川
• [Presentation] 環状過酸化化合物N-251 の生物学的利用能向上を目的とする開発研究 (2012)
  • Author(s): 片本 茜、脇本達也、渡部裕紀、森田将之、林 孝輔、佐藤 聡、綿矢有佑、高橋拓真、今田智加子、檜垣和孝、金 惠淑
  • Organizer: 第72回日本寄生虫学会東日本支部会, 第10回分子寄生虫・マラリアフォーラム
  • Place of Presentation: 前橋、群馬
• [Presentation] 薬剤耐性マラリアを如何に制御できるか?ー日本から発信する新しい抗マラリア薬ー (2012)
  • Author(s): 金 惠淑
  • Organizer: Bio Japan 2012 (World Business Forum)
  • Place of Presentation: 横浜
• [Presentation] New antimalarial endopero- xides -Bench to bed for malaria control (2012)
  • Author(s): Kim, H.-S
  • Organizer: The 5th ASEAN congress of tropical medicine and parasitology.
  • Place of Presentation: Manila, Philippine
• [Presentation] 新規抗マラリア薬・環状過酸化化合物の開発研究 (2012)
  • Author(s): 森田 将之、平本 晃子、佐藤 聡、岡田 和朗、鎌井 一気、脇本 達也、林 孝輔、片本 茜、渡部 裕紀、高橋 拓真、今田 智加子、平岡 修、野島 正朋、檜垣 和孝、綿矢有佑,金 惠淑
  • Organizer: 日本薬学会第132 年会
  • Place of Presentation: 札幌
• [Presentation] 環状過酸化化合物N-251の生物学的利用能向上を目的とする開発研究 (2012)
  • Author(s): 片本 茜、脇本達也、渡部裕紀、森田将之、林 孝輔、佐藤 聡、綿矢有佑、高橋拓真、今田智加子、檜垣和孝、金 惠淑
  • Organizer: 第72回日本寄生虫学会東日本支部会, 第10回分子寄生虫・マラリアフォーラム
  • Place of Presentation: 前橋、群馬
• [Presentation] Drug development research for antimalarial endoperoxide N-251 (2012)
  • Author(s): Masayuki Morita, Akiko Hiramoto, Kazuaki Okada, Tatsuya Wakimoto, Akane Katamoto, Hiroki Watanabe, Takuma Takahashi, Chikako Imada, Akira Sato, Kazutaka Higaki, Yusuke Wataya, Hye-Sook Kim
  • Organizer: Forum Cheju 15; The 15th Japan-Korea Parasitologists’ Seminar
  • Place of Presentation: Miyazaki, Japan
• [Presentation] The antimalarial activity of cyclic peroxides (2012)
  • Author(s): Wen Jiang, Akira Sato, Masaki Kamata, Hye-Sook Kim
  • Organizer: Forum Cheju 15; The 15th Japan-Korea Parasitologists’ Seminar
  • Place of Presentation: Miyazaki, Japan
• [Presentation] 合成環状過酸化化合物N-89投与によるマンソン住血吸虫体内のヘモゾイン蓄積量に与える影響 (2011)
  • Author(s): 谷口斎恵、熊谷貴、下河原理江子、平本晃子、佐藤聡、金惠淑、綿矢有佑、太田伸生
  • Organizer: 第80回日本寄生虫学会大会
  • Place of Presentation: 東京
  • Year and Date: 2011-07-18
• [Presentation] 新規抗住血吸虫薬の開発研究 (2010)
  • Author(s): 金 惠淑、平本晃子、佐藤 聡、森田将之、熊谷 貴、下河原理江子、谷口斎恵、奈良 武司、太田伸生、綿矢有佑
  • Organizer: 第33回日本分子生物学会年会、第83回日本生化学会大会 合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-08
• [Presentation] 新規抗住血吸虫薬の開発研究 (2010)
  • Author(s): 金惠淑、平本晃子、佐藤聡、森田将之、熊谷貴、下河原理江子、谷口斎恵、奈良武司、太田伸生、綿矢有佑
  • Organizer: 第33回 日本分子生物学会年会 第83回 日本生化学会大会 合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-08
• [Presentation] 環状過酸化化合物N-89投与時のマンソン住血吸虫プロテオーム解析 (2010)
  • Author(s): 平本晃子、佐藤聡、森田将之、綿矢有佑、熊谷貴、下河原理江子、谷口斎恵、太田伸生、金惠淑
  • Organizer: 第79回 日本寄生虫学会大会
  • Place of Presentation: 旭川
  • Year and Date: 2010-05-21
• [Presentation] 合成環状過酸化化合物N-89投与によるマンソン住血吸虫のヘモグロビン代謝への影響 (2010)
  • Author(s): 谷口斎恵、熊谷貴、下河原理江子、平本晃子、佐藤聡、金惠淑、綿矢有佑、太田伸生
  • Organizer: 第79回 日本寄生虫学会大会
  • Place of Presentation: 旭川
  • Year and Date: 2010-05-21
• [Book] 薬剤耐性マラリアに対する新規治療薬開発の現況。最新医学、67 (11) (2012)
  • Author(s): 金 惠淑、佐藤 聡、森田将之、綿矢有佑
• [Book] 旅行医学・旅行薬学の視点より論考する釜山(韓国)-心身の健康対策と旅による薬学的知見-。松山大学論集23(6 (2012)
  • Author(s): 牧純、玉井栄治、関谷洋志、廣瀬恭子、秋山伸二、難波弘行、金 惠淑、坂上 宏
• [Book] 最新医学「感染症医薬品開発の現状」薬剤耐性マラリアに対する新規治療薬開発の現状 (2012)
  • Author(s): 金 惠淑、佐藤 聡、森田将之、綿矢有佑
  • Publisher: 最新医学社
• [Book] 薬学の新領域としての「旅行医学」の提唱。愛媛県病薬会誌通巻 109号 (2011)
  • Author(s): 牧純、難波弘行、秋山伸二、玉井栄治、関谷洋志、金 惠淑、廣瀬恭子、坂上宏、柴田和彦、八重徹司、山口功、相良英憲、出石文男
• [Book] 核膜の裏打ちタンパク質Lamin-B1。生体の科学, Vol.62 (5) (2011)
  • Author(s): 佐藤聡、金 惠淑、綿矢有佑
• [Remarks]
  • URL: http://www.pharm.okayama-u.ac.jp/lab/joho/research/02.html
• [Remarks]
  • URL: http://www.pharm.okayama-u.ac.jp/lah/joho/