Structure elucidation of developmental-stage selective cell function regulators that control cellular differentiation

• Project/Area Number: 18K05335
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 37020:Chemistry and chemical methodology of biomolecules-related
• Research Institution: Hiroshima University
• Principal Investigator: Ohta Shinji 広島大学, 統合生命科学研究科(生), 教授 (60185270)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 生物活性物質 / 軟体サンゴ / 昆虫 / 植物 / 生理活性物質 / 棘皮動物 / 胚発生 / 海綿 / 海洋生物 / 細胞分化阻害 / 胚発生阻害

Outline of Final Research Achievements

For the purpose of developing useful cell function regulators, we searched for bioactive natural products that selectively arrest the progression of embryonic development of starfish at the late blastula stage. Bioassay-guided fractionation of the crude extracts resulted in the isolation of new macrocyclic diterpenoids, new sulfated purine glycosides, and new phenanthrene derivatives with an oxadinone ring from soft corals collected in the Red Sea, metabolites of seed-eating bruchid beetles, and roots of Asarum sp. Their structures were elucidated based on NMR and MS spectral data as well as X-ray crystallography. Several of these compounds have been found to inhibit cancer cell proliferation and induce apoptosis.

Academic Significance and Societal Importance of the Research Achievements

海洋生物、昆虫および植物などから得られた新規な骨格構造を有する天然有機化合物は極めて選択的な生理活性を示すことから、モデル生物でもあるイトマキヒトデの胚発生過程における細胞分化などの重要なイベントのメカニズムを明らかにするための有用なツールとなる新規細胞機能調節物質の開発につながるという学術的な意義を有しているとともに、これまでに知られていない作用機構を持った抗がん剤や抗ウィルス剤など有用な医薬品開発のためのリード化合物となりうることも期待される。

Research Products

• [Int'l Joint Research] National Research Centre(エジプト)
• [Int'l Joint Research] MSU-Iligan Institute of Technology(フィリピン)
• [Int'l Joint Research] National Research Centre(エジプト)
• [Int'l Joint Research] MSU-Iligan Institute of Technology(フィリピン)
• [Int'l Joint Research] National Research Centre(エジプト)
• [Int'l Joint Research] MSU-Iligan Institute of Technology(フィリピン)
• [Journal Article] Carotane sesquiterpenes from Ferula vesceritensis: in silico analysis as SARS-CoV-2 binding inhibitors (2020)
  • Author(s): Mohamed Tarik A.、Elshamy Abdelsamed I.、Ibrahim Mahmoud A. A.、Zellagui Ammar、Moustafa Mahmoud F.、Abdelrahman Alaa H. M.、Ohta Shinji、Pare Paul W.、Hegazy Mohamed-Elamir F.
  • Journal Title: RSC Advances Volume: 10 Issue: 57 Pages: 34541-34548
  • DOI: 10.1039/d0ra06901a
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Asaroidoxazines from the Roots of Asarum asaroides Induce Apoptosis in Human Neuroblastoma Cells (2020)
  • Author(s): Ohta Shinji、Oshimo Shiori、Ohta Emi、Nehira Tatsuo、Omura Hisashi、Uy Mylene M.、Ishihara Yasuhiro
  • Journal Title: Journal of Natural Products Volume: 83 Issue: 10 Pages: 3050-3057
  • DOI: 10.1021/acs.jnatprod.0c00574
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Rare sulfated purine alkaloid glycosides from Bruchidius dorsalis pupal case (2020)
  • Author(s): Uyama Yuri、Ohta Emi、Harauchi Yui、Nehira Tatsuo、Omura Hisashi、Kawachi Hiroyuki、Imamura-Jinda Aya、Uy Mylene M.、Ohta Shinji
  • Journal Title: Phytochemistry Letters Volume: 35 Pages: 10-14
  • DOI: 10.1016/j.phytol.2019.10.008
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Nuclear magnetic resonance spectroscopy and mass spectrometry data for sulfated isoguanine glycosides (2020)
  • Author(s): Uyama Yuri、Ohta Emi、Harauchi Yui、Nehira Tatsuo、Omura Hisashi、Kawachi Hiroyuki、Imamura-Jinda Aya、Uy Mylene M.、Ohta Shinji
  • Journal Title: Data in Brief Volume: 28 Pages: 105032-105032
  • DOI: 10.1016/j.dib.2019.105032
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Norbisabolane and bisabolane sesquiterpenoids from the seeds of Angelica keiskei (2019)
  • Author(s): Ohta Shinji、Yuasa Yasunori、Aoki Nobuwa、Ohta Emi、Nehira Tatsuo、Omura Hisashi、Uy Mylene M.
  • Journal Title: Phytochemistry Letters Volume: 33 Pages: 94-101
  • DOI: 10.1016/j.phytol.2019.08.006
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Sarcoehrenbergilides D-F: cytotoxic cembrene diterpenoids from the soft coral Sarcophyton ehrenbergi (2019)
  • Author(s): Hegazy Mohamed-Elamir F.、Mohamed Tarik A.、Elshamy Abdelsamed I.、Hamed Ahmed R.、Ibrahim Mahmoud A. A.、Ohta Shinji、Umeyama Akemi、Pare Paul W.、Efferth Thomas
  • Journal Title: RSC Advances Volume: 9 Issue: 47 Pages: 27183-27189
  • DOI: 10.1039/c9ra04158c
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] NMR and ESIMS data for bisabolane-type sesquiterpenoids (2019)
  • Author(s): Ohta Shinji、Yuasa Yasunori、Aoki Nobuwa、Ohta Emi、Nehira Tatsuo、Omura Hisashi、Uy Mylene M.
  • Journal Title: Data in Brief Volume: 27 Pages: 104780-104780
  • DOI: 10.1016/j.dib.2019.104780
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Sulfated Purine Alkaloid Glycosides from the Pupal Case Built by the Bruchid Beetle Bruchidius dorsalis Inside the Seed of Gleditsia japonica (2018)
  • Author(s): Harauchi Yui、Muranaka Kyo、Ohta Emi、Kawachi Hiroyuki、Imamura-Jinda Aya、Nehira Tatsuo、Omura Hisashi、Ohta Shinji
  • Journal Title: Chemistry & Biodiversity Volume: 15 Issue: 8
  • DOI: 10.1002/cbdv.201800154
  • Peer Reviewed
• [Journal Article] 4′,6-Dimethoxyisoflavone-7-O-β-d-glucopyranoside (wistin) is a peroxisome proliferator-activated receptor α (PPARα) agonist in mouse hepatocytes (2018)
  • Author(s): Suzuki Misato、Nakamura Fumiya、Taguchi Emi、Nakata Maho、Wada Fumi、Takihi Momoka、Inoue Tomoyo、Ohta Shinji、Kawachi Hiroyuki
  • Journal Title: Molecular and Cellular Biochemistry Volume: 446 Issue: 1-2 Pages: 35-41
  • DOI: 10.1007/s11010-018-3270-7
  • Peer Reviewed
• [Journal Article] Cytotoxicity of abietane diterpenoids from Salvia multicaulis towards multidrug-resistant cancer cells (2018)
  • Author(s): Hegazy Mohamed-Elamir F.、Hamed Ahmed R.、El-Halawany Ali M.、Hussien Taha A.、Abdelfatah Sara、Ohta Shinji、Pare Paul W.、Abdel-Sattar Essam、Efferth Thomas
  • Journal Title: Fitoterapia Volume: 130 Pages: 54-60
  • DOI: 10.1016/j.fitote.2018.08.002
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Hydroxylated furanoditerpenoids from pupal cases produced by the bruchid beetle Sulcobruchus sauteri inside the seeds of Caesalpinia decapetala (2018)
  • Author(s): Akihara Yui、Kamikawa Sayuri、Harauchi Yui、Ohta Emi、Nehira Tatsuo、Omura Hisashi、Ohta Shinji
  • Journal Title: Phytochemistry Volume: 156 Pages: 151-158
  • DOI: 10.1016/j.phytochem.2018.09.007
  • Peer Reviewed
• [Journal Article] HPLC profiles and spectroscopic data of cassane-type furanoditerpenoids (2018)
  • Author(s): Akihara Yui、Kamikawa Sayuri、Harauchi Yui、Ohta Emi、Nehira Tatsuo、Omura Hisashi、Ohta Shinji
  • Journal Title: Data in Brief Volume: 21 Pages: 1076-1088
  • DOI: 10.1016/j.dib.2018.10.068
  • Peer Reviewed / Open Access
• [Presentation] Four new oligorhamnosylferulate esters isolated from leaves of Ficus nota (2019)
  • Author(s): Felmer S. Latayada, Mylene M. Uy, Emi Ohta, Shinji Ohta
  • Organizer: 1st International Conference in Science and Mathematics (ICSM 2019)
  • Int'l Joint Research
• [Presentation] ジャノヒゲ種子に含まれる新規長鎖アナカルジン酸誘導体類の構造と生理活性 (2019)
  • Author(s): 竹田 愛実、太田 恵美、根平 達夫、大村 尚、太田 伸二
  • Organizer: 第63回 香料・テルペンおよび精油化学に関する討論会
• [Presentation] マメゾウムシ蛹室由来の新規硫酸化プリンアルカロイド類の構造と生理活性 (2019)
  • Author(s): 宇山優理、原内 優衣、太田 恵美、根平 達夫、大村 尚、河内浩行、今村(陣田)綾、太田 伸二
  • Organizer: 第63回 香料・テルペンおよび精油化学に関する討論会
• [Presentation] Anticancer property of 3-keto-20,22-dimethyl-20-deoxoscalarin isolated from Philippine marine sponge (2019)
  • Author(s): Chona Gelani, Mylene Uy, Shinji Ohta, Emi Ohta
  • Organizer: The 99th CSJ Annual Meeting
• [Presentation] ジャケツイバラ種子内に寄生するザウテルマメゾウムシの代謝成分 (2018)
  • Author(s): 秋原由依、紙川 小百合、原内 優衣、太田 恵美、根平 達夫、大村 尚、太田 伸二
  • Organizer: 第60回天然有機化合物討論会
• [Presentation] サイカチマメゾウムシにより位置選択的に硫酸化されたプレニル化プリンアルカロイド配糖体類 (2018)
  • Author(s): 原内 優衣、太田 恵美、村中 恭、河内浩行、今村(陣田)綾、根平 達夫、大村 尚、太田 伸二
  • Organizer: 第62回 香料・テルペンおよび精油化学に関する討論会