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

2012 Fiscal Year Final Research Report

• 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
• 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

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] 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] 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
  • Year and Date: 20130327-30
• [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
  • Year and Date: 20121012-13
• [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
  • Year and Date: 20121010-12
• [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
  • Year and Date: 20120515-17
• [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
  • Year and Date: 20120328-31
• [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
• [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
  • Total Pages: 74-79
• [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
  • Total Pages: 257-28
• [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
  • Total Pages: 9-20
• [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
  • Total Pages: 406-407