New Antimalarial Drug Development Research

• Project/Area Number: 22590099
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Drug development chemistry
• Research Institution: Okayama University
• Principal Investigator: KIM Hye-sook 岡山大学, 大学院・医歯薬学総合研究科, 准教授 (70314664)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2012: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 多剤耐性マラリア / 投与ルート / 抗マラリア薬効 / 有意合成化合物 / 天然生薬資源 / 体内動態 / 剤形工夫 / 医薬品化学 / マラリア / 熱帯熱マラリア / 過酸化物 / 皮下投与 / 径皮投与 / 新規治療薬 / 薬剤耐性マラリア / 有機合成化合物 / マラリア薬 / 作用機序解析 / 薬学 / 国際貢献 / 伝承薬

Research Abstract

I found several results for new antimalarial drug development study against multi-drug resistant Plasmodium falciparum.
1. A few numbers of compounds indicating the 1μM of antimalarial activity for P. falciparum (FCR-3 strain) were acquired using 40 kinds of organic synthetic compounds having peroxide structure in the body and 20 kinds of compounds from the natural product.
2. To evaluate of antimalarial activity for N-89 in clinical model system of malaria patients, N-89 has high and strong antimalarial activity in more than 5% of parasitemia of P. bergheiinfected-mice model on oral route of it.
3. I prepared several kinds of N-89 formula for long lasting effect in blood concentration of mice model. As results, the different formulation of N-89 has weak antimalarial activity compare of oil-N-89 but they did not changed pharmacokinetic parameters in mice compare of oil-N-89.

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
• [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
• [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
• [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
  • Journal Title: J Proteome Res Volume: 11 Pages: 5704-5711
  • Peer Reviewed
• [Journal Article] Andirolides HeP from the flower of andiroba (Carapa guianensis, Meliaceae) (2012)
  • Author(s): Tanaka Y
  • Journal Title: Tetrahedron Volume: 68 Pages: 3669-3677
  • 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: 488-492
  • URL: http://www.sciencedirect.com/science/article/pii/S138357691100136X
• [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
• [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 Issue: 3 Pages: 270-273
  • DOI: 10.1016/j.parint.2011.04.001
  • 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 Issue: 4 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, A., Masuyama, A., Nojima, M., Wataya, Y., Kim, H.-S.
  • Journal Title: Parasitology Intentional 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
• [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
• [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., Takasu, K.
  • Journal Title: Chemical Science Volume: 1(2) Pages: 206-209
  • Peer Reviewed
• [Journal Article] Geranyl derivatives 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, YN., Wu, PC., Bastow, KF., Akiyama, T., Lee, KH.
  • Journal Title: Heterocycles Volume: 81(5) Pages: 1193-1229
  • Peer Reviewed
• [Journal Article] Different Behavior of Artemisinin and Tetraoxane in the Oxidative Degradation of Phospholipid. (2009)
  • Author(s): Kumura, N., Furukawaa, H., Onyangob, A.,Izumia, M., Nakajimaa, S.,Ito, H., Hatano, T., Kim, H.-S., Wataya, Y. and Baba.
  • Journal Title: Chemistry and Physics of Lipids Volume: 160(2) Pages: 114-120
  • URL: http://www.sciencedirect.com/science/article/pii/S0009308409000796
• [Journal Article] Synthesis of novel conjugates of tetraoxane endoperoxide with bis (quaternary ammonium salts). (2009)
  • Author(s): Kumura, N., Furukawa, H., Kobayashi, M., Onyango, A. N., Izumi, M., Nakajima, S., Kim, H.-S., Wataya, Y. and Baba, N.
  • Journal Title: Biosci. Biotecgnol. Biochem. Volume: 73 (1) Pages: 217-220
  • URL: https://www.jstage.jst.go.jp/article/bbb/73/1/73_80571/_pdf
• [Journal Article] Applications of triphenylpyrylium salt-sensitized electron transfer photo-oxygenation reactions to the synthesis of benzo-fused 1,4-diary1-2,3-dioxabicyclo[2.2.2]octanes as new antimalarial cyclic peroxides
  • Author(s): Kamata, M., Hagiwara, J., Hokari, T., Suzuki, C., Fujino, R., Kobayashi, S., Kim, H.-S., Wataya, Y.
  • Journal Title: Research on Chemical Intermediate Volume: (In press)
  • Peer Reviewed
• [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] 薬剤耐性マラリアの最新の知見ー新規治療薬開発研究の現況ー (2012)
  • Author(s): 金 惠淑
  • Organizer: 第60回日本化学療法学会学術集会
  • Place of Presentation: 長崎
  • Invited
• [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 Endoperoxides - 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
• [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): 金恵淑、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、金恵淑
  • 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、金恵淑、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] 最新医学、67 (11) (2012)
  • Author(s): 金 惠淑、佐藤 聡、森田将之、綿矢 有佑
• [Remarks]
  • URL: http://www.pharm.okayama-u.ac.jp/lab/joho/