Study of novel anti-leishmanial drug

2012 Fiscal Year Final Research Report

• Project/Area Number: 23659212
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Parasitology (including Sanitary zoology)
• 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): KIM Hye-sook 岡山大学, 大学院・医歯薬学総合研究科, 准教授 (70314664) ; SATO Akira 岡山大学, 大学院・医歯薬学総合研究科, 助教 (40530663)
• Project Period (FY): 2011 – 2012
• Keywords: リーシュマニア原虫 / アンチモン製剤 / 抗リーシュマニア活性評価 / Geldanamycin / Hsp90 / Leishmania major / Leishmania donovani

Research Abstract

I performed to new drug discovery research for 68 compounds from organic compounds and natural product using promastigotes of Leishmania major. The EC50values among 2 of them for L. majorwere 42 nM and 27 nM. In contrast, Amphotericin B as a positive control was show 63 nM of EC50value for L. majorand selective toxicity of 46-fold compare tomammalian cells of it. The structure-activity relationship study will be need more. I established the mechanism analysis of HSP90 and complex relationship in L. major and also we found the high anti-leishmanial effect for HSP90 inhibitor and it’s analogs include small molecules (EC50values; 30-40 nM) against L. major promastigotes.

Research Products

• [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: 5704-11
  • 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: 3669-77
  • URL: http://www.sciencedirect.com/science/article/pii/S0040402011019727
  • 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: Parasitology International Volume: 60 Pages: 270-3
  • URL: http://dx.doi.org/10.1016/j.parint.2011.04.001
  • Peer Reviewed
• [Journal Article] Schistosomicidal and antifecundity effects of oral treatment of synthetic endo-peroxide 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: Parasitology International Volume: 60 Pages: 231-6
  • URL: http://dx.doi.org/10.1016/j.parint.2011.02.007
  • 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 HS.
  • Journal Title: Parasitol. Int. Volume: 60(4) Pages: 488-92
  • URL: http://www.sciencedirect.com/science/article/pii/S138357691100136X
  • Peer Reviewed
• [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
  • Year and Date: 20130327-30
• [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
  • Year and Date: 20130327-30
• [Presentation] The antimalarial activity of cyclic peroxides. Forum Cheju 15; (2012)
  • Author(s): Wen Jiang, Akira Sato, Masaki Kamata, Hye-Sook Kim.
  • Organizer: The 15th Japan-Korea Parasitologists, Seminar
  • Place of Presentation: Miyazaki, Japan
  • Year and Date: 20120523-25
• [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] 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