• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Development of extraction techniques for natural products and discovery of hyaluronan-degrading enzyme inhibitors from natural products

Research Project

Project/Area Number 26870217
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field General internal medicine(including psychosomatic medicine)
Natural medicines
Research InstitutionUniversity of Toyama

Principal Investigator

TOMOHARA KEISUKE  富山大学, 附属病院, 助教 (40711677)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords生薬 / 多成分の分子変換 / アミノ酸誘導体 / ヒダントイン / ヒアルロニダーゼ / 化学的摂動効果 / ジメチルスルホキシド / 非特異的分子間相互作用 / 多成分系の分子変換 / ヒアルロン酸分解酵素 / 化学的直接誘導化 / 非特異的阻害剤 / 複雑系 / 生薬成分抽出 / 化学的一挙誘導化
Outline of Final Research Achievements

We have achieved direct chemical derivatization of natural plant extracts, where electrophilic ketones in the extracts could be selectively converted into the corresponding hydantoins (imidazolidine-2,4-dione) under the Bucherer-Bergs reaction conditions. The derivatization proceeded with enough chemoselectivity, minimizing the complication of the reaction system, and thus realizing the facile identification of unnatural hydantoins from the derivatized extracts.
We have also developed new methodology to highlight promiscuous non-specific binding inhibitors of enzymes by interpreting the behavior of concentration-response curves under in vitro DMSO-perturbing assay conditions. Furthermore, we have discovered novel inhibitors of hyaluronan-degrading enzyme from natural plant extracts.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (23 results)

All 2017 2016 2015 2014

All Journal Article (4 results) (of which Peer Reviewed: 3 results,  Acknowledgement Compliant: 3 results) Presentation (19 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Discovery of hyaluronidase inhibitors from natural products and their mechanistic characterization under DMSO-perturbed assay conditions2017

    • Author(s)
      Keisuke Tomohara, Tomohiro Ito, Saika Onikata, Atsushi Kato, Isao Adachi
    • Journal Title

      Bioorganic & Medicinal Chemistry Letters

      Volume: 27 Issue: 7 Pages: 1620-1623

    • DOI

      10.1016/j.bmcl.2017.01.083

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Interpreting the behavior of concentration-response curves of hyaluronidase inhibitors under DMSO-perturbed assay conditions2016

    • Author(s)
      Keisuke Tomohara, Tomohiro Ito, Saika Onikata, Kota Furusawa, Atsushi Kato, Isao Adachi
    • Journal Title

      Bioorganic & Medicinal Chemistry Letters

      Volume: 26 Issue: 13 Pages: 3153-3157

    • DOI

      10.1016/j.bmcl.2016.04.082

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Another aspect in use of DMSO in medicinal chemistry2016

    • Author(s)
      Keisuke Tomohara
    • Journal Title

      Atlas of Science

      Volume: -

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Direct chemical derivatization of natural plant extract: straightforward synthesis of natural plant-like hydantoin2016

    • Author(s)
      Keisuke Tomohara, Tomohiro Ito, Naoto Hasegawa, Atsushi Kato, Isao Adachi
    • Journal Title

      Tetrahedron Letters

      Volume: 57 Issue: 8 Pages: 924-927

    • DOI

      10.1016/j.tetlet.2016.01.054

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] DMSO摂動条件下での酵素阻害剤の分子間相互作用様式の解析2017

    • Author(s)
      友原啓介,加藤敦,足立伊佐雄
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台
    • Related Report
      2016 Annual Research Report
  • [Presentation] 極性変換を鍵とする多成分系の分子変換2017

    • Author(s)
      古沢晃太,友原啓介,長谷川直人,加藤敦,足立伊佐雄
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台
    • Related Report
      2016 Annual Research Report
  • [Presentation] ピロリジン型イミノ糖を基盤とした新規GCase高親和性リガンドのデザインとファーマコジカルシャペロン効果について2016

    • Author(s)
      加藤敦,山本亜里紗,友原啓介,足立伊佐雄,渡邊靖香,名取良浩,吉村祐一,中込泉,広野修一
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-03-26
    • Related Report
      2015 Research-status Report
  • [Presentation] 生薬抽出エキスの化学的直接誘導化2016

    • Author(s)
      友原啓介
    • Organizer
      平成28年度北信越有機合成化学若手の会
    • Place of Presentation
      金沢
    • Related Report
      2016 Annual Research Report
  • [Presentation] DMSO添加条件下におけるヒアルロニダーゼ阻害剤の活性部位特異性の評価2016

    • Author(s)
      友原啓介,伊藤智裕,鬼形彩花,加藤敦,足立伊佐雄
    • Organizer
      日本生薬学会第63回年会
    • Place of Presentation
      富山
    • Related Report
      2016 Annual Research Report
  • [Presentation] 多成分からなる生薬抽出エキスの化学的直接誘導化による非天然型アミノ酸等価体の一挙創製2016

    • Author(s)
      古沢晃太,友原啓介,長谷川直人,伊藤智裕,加藤敦,足立伊佐雄
    • Organizer
      日本生薬学会第63回年会
    • Place of Presentation
      富山
    • Related Report
      2016 Annual Research Report
  • [Presentation] Synthesis of alpha,alpha-disubstituted hydantoins through chemoselective derivatization of natural product extracts2015

    • Author(s)
      Keisuke Tomohara, Atsushi Kato, Isao Adachi
    • Organizer
      2015 International Chemical Congress of Pacific Basin Societies
    • Place of Presentation
      Honolulu
    • Year and Date
      2015-12-15
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Protective effects of dietary 1,5-Anhydro-D-glucitol in diabetes and metabolic syndrome2015

    • Author(s)
      Atsushi Kato, Keisuke Tomohara, Isao Adachi, Fumihiro Ishikawa, Kei Takeshita, Jacqueline Hollinshead, Robert Nash, Zilei Liu, Sarah Jenkinson, George Fleet
    • Organizer
      2015 International Chemical Congress of Pacific Basin Societies
    • Place of Presentation
      Honolulu
    • Year and Date
      2015-12-15
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 生薬からのヒスチジン脱炭酸酵素阻害物質の探索研究2015

    • Author(s)
      荻原孝史,上出真由,須永百合枝,数馬恒平,紺野勝弘,友原啓介,加藤敦,足立伊佐雄
    • Organizer
      日本薬学会北陸支部第127回例会
    • Place of Presentation
      富山
    • Year and Date
      2015-11-15
    • Related Report
      2015 Research-status Report
  • [Presentation] 化学的摂動法を利用した複雑系生薬研究への挑戦2015

    • Author(s)
      友原啓介
    • Organizer
      平成27年度富山大学若手研究者等の学術交流・発表会
    • Place of Presentation
      富山
    • Year and Date
      2015-09-08
    • Related Report
      2015 Research-status Report
  • [Presentation] 生薬抽出エキスの一挙誘導化によるαーアミノ酸誘導体の創製研究2015

    • Author(s)
      友原啓介,伊藤智裕,長谷川直人,加藤敦,足立伊佐雄
    • Organizer
      フォーラム富山「創薬」第41回研究会
    • Place of Presentation
      富山
    • Year and Date
      2015-05-28
    • Related Report
      2015 Research-status Report
  • [Presentation] 副作用の少ない次世代型食後過血糖改善薬のデザイン研究2015

    • Author(s)
      加藤敦,広上由季,木南今日子,友原啓介,足立伊佐雄
    • Organizer
      フォーラム富山「創薬」第41回研究会
    • Place of Presentation
      富山
    • Year and Date
      2015-05-28
    • Related Report
      2015 Research-status Report
  • [Presentation] 化学的摂動効果を利用した複雑系漢方研究への挑戦2015

    • Author(s)
      友原啓介
    • Organizer
      2015年度北信越有機合成化学若手の会
    • Place of Presentation
      富山
    • Year and Date
      2015-04-04
    • Related Report
      2015 Research-status Report
  • [Presentation] ヒアルロン酸分解酵素活性評価系におけるDMSO添加効果2015

    • Author(s)
      友原啓介、伊藤智裕、加藤敦、足立伊佐雄
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      神戸市
    • Year and Date
      2015-03-28
    • Related Report
      2014 Research-status Report
  • [Presentation] 食後過血糖及び食後高脂血症に対する改善効果が期待される1,5-Anhydro-D-glucitolの有効性と作用メカニズムについて2015

    • Author(s)
      加藤敦、渡辺優樹、辻祐太朗、友原啓介、足立伊佐雄、松上真也、竹下圭、石川文博
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      神戸市
    • Year and Date
      2015-03-27
    • Related Report
      2014 Research-status Report
  • [Presentation] イミノ糖を基盤とした副作用の少ない食後過血糖改善薬の開発研究2015

    • Author(s)
      木南今日子、加藤敦、広上由季、友原啓介、中込泉、広野修一、足立伊佐雄
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      神戸市
    • Year and Date
      2015-03-27
    • Related Report
      2014 Research-status Report
  • [Presentation] イミノ糖を基盤とした次世代型グルコシルトランスフェラーゼ阻害薬の開発基礎研究2015

    • Author(s)
      神守彰子、加藤敦、岩城蓮、友原啓介、足立伊佐雄
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      神戸市
    • Year and Date
      2015-03-27
    • Related Report
      2014 Research-status Report
  • [Presentation] 活性部位特異的なヒアルロニダーゼ阻害剤の探索2015

    • Author(s)
      伊藤智裕、友原啓介、鬼形彩花、加藤敦、足立伊佐雄
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      神戸市
    • Year and Date
      2015-03-26
    • Related Report
      2014 Research-status Report
  • [Presentation] C-N軸性不斉エノラートを経るアミノ酸誘導体の不斉記憶型α-アリール化の開発2014

    • Author(s)
      笠松幸司、友原啓介、百武龍一、楊畔、吉村智之、川端猛夫
    • Organizer
      モレキュラーキラリティー2014
    • Place of Presentation
      仙台市
    • Year and Date
      2014-06-07
    • Related Report
      2014 Research-status Report

URL: 

Published: 2014-04-04   Modified: 2018-03-22  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi