Development of specific inhibitors of juvenile hormone(JH)and their application for elucidation of mechanism of JH action

• Project/Area Number: 17208007
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied entomology
• Research Institution: Kyushu University
• Principal Investigator: KUWANO Eiichi Kyushu University, 大学院・農学研究院, 教授 (00108672)
• Co-Investigator(Kenkyū-buntansha): 塩月 孝博 九州大学, 農業生物資源研究所, 研究チーム長 (80355734) ; 篠田 徹郎 九州大学, 農業生物資源研究所, 主任研究官 (10355620)
• Co-Investigator(Renkei-kenkyūsha): SHIOTSUKI Takahiro 農業生物資源研究所, 主任研究員 (80355734) ; SHINODA Tetsuro 農業生物資源研究所, 主任研究員 (10355620)
• Project Period (FY): 2005 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥35,880,000 (Direct Cost: ¥27,600,000、Indirect Cost: ¥8,280,000); Fiscal Year 2008: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000); Fiscal Year 2007: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000); Fiscal Year 2006: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000); Fiscal Year 2005: ¥14,170,000 (Direct Cost: ¥10,900,000、Indirect Cost: ¥3,270,000)
• Keywords: 幼若ホルモン / 抗幼若ホルモン / カイコ / 早熟変態 / 成育制御剤 / クロメン誘導体 / インドール誘導体 / ベンゾジオキサン誘導体 / インドリン誘導体 / エポキシダーゼ / 幼若ホルモンエステラーゼ / アポリポフォリンIII / 体液タンパク質 / 幼若ホルモン生合成 / メチル基転移酵素 / アリルフォリン

Research Abstract

昆虫の各成育段階において多様な生理作用を示す幼若ホルモン(JH)の作用機構の解明に役立つ分子プローブとして、また、新規昆虫成育制御剤のリード化合物となりうる数種のJH特異的阻害剤を分子設計・創製した。阻害剤の構造は、活性発現に共通な必須部位と、それ以外のアルキル鎖、芳香環あるいは複素環から成り立っており多様であった。これらはカイコ幼虫に対して、体液中のJH濃度を顕著に低下させたことから、その作用機構はアラタ体におけるJH生合成阻害と考えられる。

Research Products

• [Journal Article] Ethyl 4-[(1-sub-stituted indol-2-yl)methoxy]benzo-ates and indoline derivatives : Anti-juvenile hormone and juvenile hormone activities (2009)
  • Author(s): Kenjiro Furuta, Shuhei Yoshida, Norihiro Fujita, Naotaka Yamada and Eiichi Kuwano
  • Journal Title: J. Pestic. Sci. (in press)
  • NAID: 130004445157
  • Peer Reviewed
• [Journal Article] Ethyl 4-[2-(Substi-tuted Benzyl)hexyloxy]benzoates : Anti-Juvenile Hormone Agents with Juvenile Hormone Activity (2009)
  • Author(s): Shuhei Yoshida, Kenjiro Furuta, Kiyo Ashibe, Norihiro Fujita, Seiji Nishikawa, Naotaka Yamada and Eiichi Kuwano
  • Journal Title: J. Fac. Agr., Kyushu Univ. 54 Pages: 185-190
• [Journal Article] Synthesis and Struc-ture-Activity Relationship of a New Series of Anti-Juvenile Hormone Agents : Alkyl 4-(2-Benzylhexyloxy)-benzoates and Ethyl 4-Substituted Benzoates (2009)
  • Author(s): Shuhei Yoshida, Kenjiro Furuta, Hiromitsu Shirahashi, Kiyo Ashibe, Norihiro Fujita, Naotaka Yamada and Eiichi Kuwano
  • Journal Title: J. Fac. Agr., Kyushu Univ. 54 Pages: 179-184
• [Journal Article] Synthesis and structure-activity relationship of a new series of anti-juvenile hormone agents : Alkyl 4-(2-benzylhexyloxy)benzoates and Ethyl 4-substituted benzoates (2009)
  • Author(s): Yoshida, et al.
  • Journal Title: Journal of the Faculty of Agriculture, Kyushu University 54 Pages: 179-184
• [Journal Article] Ethyl 4-[2-(substituted benzyl)hexyloxy]benzoates : Anti-juvenile hormone Agents with juvenile hormone activity (2009)
  • Author(s): Yoshida, et al.
  • Journal Title: Journal of the Faculty of Agriculture, Kyushu University 54 Pages: 185-190
• [Journal Article] Ethyl 4-[(1-substituted indol-2-yl)methoxy]benzoates and indoline derivatives : Anti-juvenile hormone and juvenile hormone activities (2009)
  • Author(s): Furuta, et al.
  • Journal Title: Journal of Pesticide Science 34(In press)
  • Peer Reviewed
• [Journal Article] Juvenile hormone activity of optically active ethyl 4-(2-benzylalkyloxy)benzoates inducing precocious metamorphosis (2008)
  • Author(s): Norihiro Fujita, Kenjiro Furuta, Kiyo Ashibe, Shuhei Yoshida, Naotaka Yamada, Takahiro Shiotsuki, Makoto Kiuchi and Eiichi Kuwano
  • Journal Title: J. Pestic. Sci. 33 Pages: 383-386
  • NAID: 110006989913
  • Peer Reviewed
• [Journal Article] Juvenile hormone activity of optically active ethyl 4-(2-benzylalkyloxy)-Benzoates inducing precocious metamorphosis (2008)
  • Author(s): Fujita, et al.
  • Journal Title: Journal of Pesticide Science 33 Pages: 383-386
  • Peer Reviewed
• [Journal Article] Synthesis and biological activity of novel anti-juvenile hormone agents (2008)
  • Author(s): E.Kuwano, et. al.
  • Journal Title: Journal of Pesticide Science 33 Pages: 14-16
  • NAID: 110006614063
  • Peer Reviewed
• [Journal Article] Juvenile hormone activity of ethyl 4-(2-aryloxybexyloxy)benzoates with precocious metamorphosis-inducing activity (2007)
  • Author(s): Norihiro Fujita, Kiyo Ashibe, Naotaka Yamada, Takahiro Shiotsuki, Makoto Kiuchi and Eiichi Kuwano
  • Journal Title: Biosci. Biotechnol. Biochem. 71 Pages: 2333-2334
  • Peer Reviewed
• [Journal Article] Synthesis and anti-juvenile hormone activity of ethyl 4-(2-benzylalkyloxy)benzoates and their enantiomers (2007)
  • Author(s): Kenjiro Furuta, Kiyo Ashibe, Hiromitsu Shirahashi, Norihiro Fujita, Haruna Yamashita, Naotaka Yamada and Eiichi Kuwano
  • Journal Title: J. Pestic. Scil 32 Pages: 99-105
  • NAID: 110006273852
  • Peer Reviewed
• [Journal Article] Juvenile hormone activity of ethyl 4-(2-aryloxyhexyloxy)benzoates with Precocious metamorphosis-inducing activity (2007)
  • Author(s): N.Fujita, et. al.
  • Journal Title: Bioscience, Biotechnology and Biochemistry 71 Pages: 2333-2334
  • Peer Reviewed
• [Journal Article] Synthesis and anti-juvenile hormone activity of ethyl 4-(2-benzylalkyloxy) benzoates and their enantiomers (2007)
  • Author(s): K.Furuta et al.
  • Journal Title: Journal of Pesticide Science 32 (In press)
• [Journal Article] Synthesis and anti-juvenile hormone activity of alkyl 4-(2-phenoxyalkyloxy)benzoates and related compounds (2006)
  • Author(s): Kenjiro Furuta, Hiromitsu Shirahashi, Kiyo Ashibe, Haruna Yamashita, Seiji Nishikawa, Norihiro Fujita, Naotaka Yamada and Eiichi Kuwano
  • Journal Title: J. Fac. Agr., Kyushu Univ. 51 Pages: 303-308
• [Journal Article] Synthesis and anti-juvenile hormone activity of ethyl 4-(2-aryloxyhexyloxy)benzoates (2006)
  • Author(s): Kenjiro Furuta, Hiromitsu Shirahashi, Haruna Yamashita, Kiyo Ashibe and Eiichi Kuwano
  • Journal Title: Biosci. Biotechnol. Biochem 70 Pages: 746-748
  • NAID: 10018533784
  • Peer Reviewed
• [Journal Article] Synthesis and anti-juvenile hormone activity of alkyl 4-(2-phenoxyalkyloxy) benzoates and related compounds (2006)
  • Author(s): K.Furuta et al.
  • Journal Title: Journal of the Faculty of Agriculture, Kyushu University 51・2 Pages: 303-308
• [Journal Article] Synthesis and anti-juvenile hormone activity of ethyl 4-(2-Aryloxyhexyloxy)benzoates (2006)
  • Author(s): K.Furuta et al.
  • Journal Title: Bioscience, Biotechnology and Biochemistry 70(In press)
• [Journal Article] Synthesis and anti-juvenile hormone activity of ethyl 4-[2-(6-methyl-3-pyridyloxy)alkyloxy]benzoates (2005)
  • Author(s): Norihiro Fujita, Kenjiro Furuta, Hiromitsu Shirahashi, Soonsung Hong, Takahiro Shiotsuki and Eiichi Kuwano
  • Journal Title: J. Pestic. Sci. 30 Pages: 192-198
  • NAID: 110001788820
  • Peer Reviewed
• [Presentation] 1,4-benzodioxan環を有する抗JH活性物質の創製 (2009)
  • Author(s): 中村美穂
  • Organizer: 日本農芸化学会2009年度大会
  • Place of Presentation: 福岡
  • Year and Date: 2009-09-29
• [Presentation] 早熟変態誘導活性物質KF-13のカイコ体液中の昆虫ホルモンに与える影響 (2009)
  • Author(s): 古田賢次郎, et al.
  • Organizer: 日本農芸化学会2009年度大会
  • Place of Presentation: 福岡
  • Year and Date: 2009-03-29
• [Presentation] 1, 4-benzodioxan環を有する抗JH活性物質の創製 (2009)
  • Author(s): 中村美穂, et al.
  • Organizer: 日本農芸化学会2009年度大会
  • Place of Presentation: 福岡
  • Year and Date: 2009-03-29
• [Presentation] カイコの早熟変態誘導の機能解析 (2009)
  • Author(s): 塩月孝博, et al
  • Organizer: 日本農芸化学会2009年度大会
  • Place of Presentation: 福岡
  • Year and Date: 2009-03-29
• [Presentation] chromene環を有する新規抗幼若ホルモン活性物質の合成とKF-38の体液中のJH濃度に与える影響 (2009)
  • Author(s): 古田賢次郎
  • Organizer: 日本農薬学会第34回大会
  • Place of Presentation: 東京
  • Year and Date: 2009-03-19
• [Presentation] クロメン及びベンゾジオキサン環を有する新規昆虫成育制御剤の合成探索 (2008)
  • Author(s): 山路英臣, et al
  • Organizer: 日本農芸化学会2008年度西日本支部大会
  • Place of Presentation: 長崎
  • Year and Date: 2008-09-20
• [Presentation] 含窒素複素環を有する新規抗幼若ホルモン活性物質の合成探索 (2008)
  • Author(s): 坂本佳彦, et al.
  • Organizer: 日本農芸化学会2008年度西日本支部大会
  • Place of Presentation: 長崎
  • Year and Date: 2008-09-20
• [Presentation] 早熟変態誘導物質KF-13のカイコ体液中幼若ホルモン濃度に及ぼす影響 (2008)
  • Author(s): 飯伏 翼, et al.
  • Organizer: 日本農芸化学会2008年度西日本支部大会
  • Place of Presentation: 長崎
  • Year and Date: 2008-09-20
• [Presentation] chromene環を有する新規昆虫成育制御物質の構造活性相関とその作用特性 (2008)
  • Author(s): 古田賢次郎, et al.
  • Organizer: 第45回化学関連支部合同九州大会
  • Place of Presentation: 北九州
  • Year and Date: 2008-07-05
• [Presentation] chromene環を有する新規昆虫成育制御物質の合成探索と生理活性 (2008)
  • Author(s): 古田賢次郎
  • Organizer: 日本農薬学会第33回大会
  • Place of Presentation: 奈良
  • Year and Date: 2008-03-30
• [Presentation] 新規幼若ホルモン阻害物質の分子設計および合成探索 (2008)
  • Author(s): 吉田周平
  • Organizer: 日本農芸化学会2008年度大会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-03-27
• [Presentation] Action of a novel anti-juvenile hormone agent, KF-13, in Bombyx mori larvae (2007)
  • Author(s): N. Fujita
  • Organizer: 9th International Conference on Juvenile Hormones
  • Place of Presentation: Yorkshire Museum Gardens, York U.K.
  • Year and Date: 2007-08-10
• [Presentation] Novel anti-juvenile hormone agents : Structure-activity relationship of ethyl 4-(2-substituted benzyl-alkyloxy)benzoates (2007)
  • Author(s): K. Furuta
  • Organizer: 9th International Conference on Juvenile Hormones
  • Place of Presentation: Yorkshire Museum Gardens, York U.K.
  • Year and Date: 2007-08-10
• [Presentation] Optimization of LC-MS analysis for JH concentration in larval hemolymph of silkworm, Bombyx mori. (2007)
  • Author(s): T. Shiotsuki
  • Organizer: 9th International Conference on Juvenile Hormones
  • Place of Presentation: Yorkshire Museum Gardens, York U.K.
  • Year and Date: 2007-08-10
• [Presentation] Action of a novel anti-juvenile hormone agent,KF-13,in Bombyx morilarvae. (2007)
  • Author(s): N.Fujita, et. al.
  • Organizer: 9th International Conference on Juvenile Hormones
  • Place of Presentation: York,U.K
  • Year and Date: 2007-08-10
• [Presentation] Novel anti-juvenile hormone agents: Structure-activity relationship of ethyl 4-(2-substituted benzylalkyloxy)benzoates. (2007)
  • Author(s): K.Furuta, et. al.
  • Organizer: 9th International Conference on Juvenile Hormones
  • Place of Presentation: York,U.K
  • Year and Date: 2007-08-10
• [Presentation] 新規抗幼若ホルモン活性物質ethyl 4-(2-benzylheptyloxy)benzoate(KA-1)の作用特性 (2007)
  • Author(s): 藤田雄大
  • Organizer: 第51回日本応用動物昆虫学会大会
  • Place of Presentation: 広島
  • Year and Date: 2007-03-29
• [Presentation] 4-(2-置換ベンジルアルキルオキシ)ベンゾエート類の抗幼若ホルモン活性 (2007)
  • Author(s): 西川誠志
  • Organizer: 日本農芸化学会2007年度大会
  • Place of Presentation: 東京
  • Year and Date: 2007-03-25
• [Presentation] エチル4-(2-ベンジルヘプチルオキシ)ベンゾエート(KA-1)両鏡像体の抗幼若ホルモン活性と幼若ホルモン活性 (2007)
  • Author(s): 芦邊 希代, et. al.
  • Organizer: 日本農芸化学会2007年度大会
  • Place of Presentation: 東京
• [Presentation] Synthesis and anti-juvenile hormone activity of optically active ethyl 4-(2-benzylalkyloxy)benzoates (2006)
  • Author(s): K. Ashibe
  • Organizer: 11th IUPAC International Congress of Pesticide Chemistry
  • Place of Presentation: Kobe
  • Year and Date: 2006-08-09
• [Presentation] Characterization of ethyl 4-(2-substituted alkyloxy)benzoates with precocious metamorphosis-inducing activity (2006)
  • Author(s): N. Fujita
  • Organizer: 11th IUPAC International Congress of Pesticide Chemistry
  • Place of Presentation: Kobe
  • Year and Date: 2006-08-08