Synthesis and evaluation of sulfonium-type alpha-glucosidase inhibitors based on the structure of salacinol

2013 Fiscal Year Final Research Report

• Project/Area Number: 23590140
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Drug development chemistry
• Research Institution: Kinki University
• Principal Investigator: TANABE Genzoh 近畿大学, 薬学部, 准教授 (40217104)
• Co-Investigator(Kenkyū-buntansha): MINEMATSU Toshie 近畿大学, 薬学部, 助手 (60088151)
• Project Period (FY): 2011 – 2013
• Keywords: サラシノール / α-グルコシダーゼ阻害剤

Research Abstract

To develop more potent alpha-glucosidase inhibitors whose seed-compound is salacinol (1), a potent natural alpha-glucosidase inhibitor isolated from Salacia reticulata of Ayurvedic traditional medicine, several candidates with 3'-O-alkyl (CH3, C2H5, C13H27) or benzyl groups (CH2C6H5, CH2C6H4CH3, CH2C6H5Cl, CH2C6H4CF3, CH2C6H4NO2) instead of the 3'-O-sulfate anion in 1 were synthesized. These analogs showed equal or considerably higher inhibitory activity against rat small intestinal alpha-glucosidases than 1. Among the sulfonium salts designed, one with 3'-O-(ortho-nitrobenzyl) moiety was found to be the most potent, and ca. forty times as potent as 1, the compound being the strongest inhibitor among the sulfonium type inhibitors synthesized so far.

Research Products

• [Journal Article] (2012)
  • Author(s): G. Tanabe, S. Nakamura, N. Tsutsui, G. Balakishan, W. Xie, S. Tsuchiya, J. Akaki, T. Morikawa, K. Ninomiya, I. Nakanishi, M.Yoshikawa, O. Muraoka
  • Journal Title: Chem. Commun Volume: 48 Pages: 8646–8648
  • Peer Reviewed
• [Journal Article] (2011)
  • Author(s): G. Tanabe, T. Otani, W. Cong, T. Minematsu, K. Ninomiya, M. Yoshikawa and O. Muraoka
  • Journal Title: Bioorg. Med. Chem. Lett Volume: 21 Pages: 3159–3162
• [Presentation] Structure Activity Relationship Study on Salacinol, a Potentα-Glucosidase Inhibitor from Ayurvedic Traditional Medicine"Salacia": Effect of 3'-O-Aralkylation with Toluic Acid (2013)
  • Author(s): G. Tanabe, S. Nakamura, N. Tsutsui, J. Akaki, T. Morikawa, K. Ninomiya, I. Nakanishi, M. Yoshikawa, O. Muraoka
  • Organizer: 9th AFMS International Medicinal Chemistry Symposium (AIMECS13)
  • Place of Presentation: Taipei, Taiwan
  • Year and Date: 20131016-18
• [Presentation] α-グルコシダーゼ阻害剤, Salacinolの構造活性相関研究―トルイル酸型置換基による3'位疎水化の効果― (2013)
  • Author(s): 田邉元三,中村真也,筒井望,赤木淳二,森川敏生,二宮清文,仲西功,吉川雅之,村岡修
  • Organizer: 第30回メディシナルケミストリーシンポジウム
  • Place of Presentation: 広島
  • Year and Date: 2013-11-22
• [Presentation] α-グルコシダーゼ阻害剤、salacinolの構造活性相関研究:3'位脂溶性化が活性に及ぼす効果 (2013)
  • Author(s): 田邉元三,中村真也,國方雄介,筒井望,赤木淳二,森川敏生,二宮清文,仲西功,吉川雅之,村岡修
  • Organizer: 第5回食品薬学シンポジウム
  • Place of Presentation: 京都
  • Year and Date: 2013-11-02
• [Presentation] α-グルコシダーゼ阻害剤、salacinolの構造活性相関研究:トルイル酸型置換基による3'位疎水化の効果 (2013)
  • Author(s): 田邉元三,中村真也,國方雄介,筒井望,赤木淳二,森川敏生,二宮清文,仲西功,吉川雅之,村岡修
  • Organizer: 第63回日本薬学会近畿支部総会・大会
  • Place of Presentation: 京都
  • Year and Date: 2013-10-12
• [Presentation] Salacinolをシードとするスルホニウム塩型α-グルコシダーゼ阻害剤のin silico設計,合成および評価:3'位アルキル化の効果 (2013)
  • Author(s): 田邉元三,國方雄介,中村真也,筒井望,赤木淳二,森川敏生,二宮清文,仲西功,吉川雅之,村岡修
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 横浜
  • Year and Date: 2013-03-29
• [Presentation] Salacinolをシードとするスルホニウム塩型α-グルコシダーゼ阻害剤のin silico設計,合成および評価 (2012)
  • Author(s): 田邉元三,中村真也,筒井望,赤木淳二,森川敏生,二宮清文,仲西功,吉川雅之,村岡修
  • Organizer: 第30回メディシナルケミストリーシンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2012-11-20
• [Presentation] (2012)
  • Author(s): G. Tanabe, S. Nakamura, N. Tsutsui, Masahiro Yoshinaga, Y. Kunikata, J. Akaki, T. Morikawa, K. Ninomiya,I. Nakanishi, M. Yoshikawa, O. Muraoka
  • Organizer: The 12^<th> International Kyoto Conference on New Aspects of Organic Chemistry
  • Place of Presentation: IKCOC-12, Kyoto, Japan
  • Year and Date: 2012-11-15
• [Presentation] Salacinolをシードとするスルホニウム塩型α-グルコシダーゼ阻害剤のin silico設計,合成及び評価 (2012)
  • Author(s): 田邉元三,中村真也,國方雄介,土屋聡史,吉長正紘,筒井望,赤木淳二,森川敏生,二宮清文,仲西功,吉川雅之,村岡修
  • Organizer: 第62回日本薬学会近畿支部大会
  • Place of Presentation: 武庫川
  • Year and Date: 2012-10-20
• [Presentation] Salacinolをシードとするスルホニウム塩型α-グルコシダーゼ阻害剤のin silico設計,合成及び評価 (2012)
  • Author(s): 田邉元三,中村真也,吉長正紘,筒井望,Gorre Balakishan,赤木淳二,森川敏生,二宮清文,仲西功,吉川雅之,村岡修
  • Organizer: 第54回天然有機化合物討論会
  • Place of Presentation: 東京
  • Year and Date: 2012-09-18
• [Presentation] α-Glucosidase阻害剤salacinolの構造活性相関:3'位ベンジル化の効果 (2012)
  • Author(s): 田邉元三, 土屋聡史, 筒井望, 峯松敏江, 赤木淳二, 中村真也, 仲西功, 吉川雅之, 村岡修
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 札幌
  • Year and Date: 2012-03-31
• [Presentation] α-Glucosidase阻害剤salacinolの3'位アルキル化体の合成および活性評価:3'位疎水性置換基が活性に及ぼす効果 (2012)
  • Author(s): 田邉元三, Balakishan Gorre, 筒井望, 中村真也, 仲西功, 吉川雅之, 村岡修
  • Organizer: 生物分子システムに基づく創薬科学フロンティア研究成果発表会
  • Place of Presentation: 京都
  • Year and Date: 2012-02-18
• [Presentation] Synthesis and Biological Evaluation of 3'-O-Alkylated Salacinols asα-Glucosidase Inhibitors (2011)
  • Author(s): G. Tanabe, T. Otani, H. Takemura, S. Tsuchiya, N. Tsutsui, B. Gorre, M. Yoshikawa, O. Muraoka
  • Organizer: 22^<nd> French- Japanese Symposium on Medicinal and Fine Chemistry
  • Place of Presentation: Rouen, France
  • Year and Date: 20110911-14
• [Presentation] Biological Evaluation of 3'-O-Alkylated Analogs of Salacinol, the Role of Hydrophobic Alkyl Group at 3'Position in the Side Chain on theα-Glucosidase Inhibitory Activity (2011)
  • Author(s): G. Tanabe, N. Tsutsui, M. Oka, B. Gorre, W. Xie, S. Nakamura, I. Nakanishi, M. Yoshikawa, O. Muraoka
  • Organizer: 8^<th > AFMC International Medicinal Chemistry Symposium "Frontier of Medicinal Science"
  • Place of Presentation: Tokyo
  • Year and Date: 2011-11-30
• [Presentation] Salacinolをシードとするスルホニウム塩型α-グルコシダーゼ阻害剤のin silico設計,合成及び評価 (2011)
  • Author(s): 田邉元三,中村真也,國方雄介,土屋聡史,吉長正紘,筒井望,赤木淳二,森川敏生,二宮清文,仲西功,吉川雅之,村岡修
  • Organizer: 第19回天然薬物の開発と応用シンポジウム
  • Place of Presentation: 大阪
  • Year and Date: 2011-11-01
• [Presentation] α-Glucosidase阻害剤salacinolの3'位疎水化の活性に及ぼす効果 (2011)
  • Author(s): 田邉元三, 土屋聡史, 筒井望, 赤木淳二, 中村真也, 仲西功, 吉川雅之, 村岡修
  • Organizer: 第61回日本薬学会近畿支部大会
  • Place of Presentation: 神戸
  • Year and Date: 2011-10-22
• [Presentation] Biological Evaluation of 3'-O-Alkylated Analogs of Salacinol, the Role of Hydrophobic Alkyl Group at 3'Position in the Side Chain on theα-Glucosidase Inhibitory Activity (2011)
  • Author(s): G. Tanabe, T. Otani, N. Tsutsui, H. Takemura, W. Xie, B. Gorre, M. Yoshikawa, O. Muraoka
  • Organizer: 23rd International Congress on Heterocyclic Chemistry
  • Place of Presentation: Glasgow, Scotland
  • Year and Date: 2011-08-01
• [Book] 薬用食品の開発II-薬用・有用植物の機能性食品素材への応用 (2012)
  • Publisher: シーエムシー出版