Control of epigenetics by chemical modulator based on natural products

• Project/Area Number: 15K14974
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Drug development chemistry
• Research Institution: Hokkaido University
• Principal Investigator: ICHIKAWA Satoshi 北海道大学, 薬学研究院, 教授 (60333621)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: エピジェネティックス / 創薬化学 / 抗がん剤 / 有機化学 / エピジェネテッィクス / 天然物

Outline of Final Research Achievements

Analogues of DNA bisintercalating natural products were designed and synthesized and their DNA binding properties as well as cytotoxicity against human cancer cells were evaluated. Several analogues exhibit a potent cytotoxicity against a panel of human cancer cells with nM level and some of the analogues also show in vivo antitumor activity in the experiments using mouse xenograft model. As a result, we were able to find a promising anticancer lead compound.

Research Products

• [Journal Article] Natural Product Synthesis by Multicomponent Reaction and Structure-activity Relationship Study (2016)
  • Author(s): 千葉拓也、仲谷岳志、片山勝史、松田彰、市川聡
  • Journal Title: Journal of Synthetic Organic Chemistry, Japan Volume: 74 Issue: 5 Pages: 426-440
  • DOI: 10.5059/yukigoseikyokaishi.74.426
  • NAID: 130005159415
  • ISSN: 0037-9980, 1883-6526
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Design, synthesis and biological evaluation of 5′-C-piperidinyl-5′-O-aminoribosyluridines as a potential antibacterial agent. (2015)
  • Author(s): Nakaya, Takeshi; Matsuda, Akira; Ichikawa, Satoshi*
  • Journal Title: Org. Biomol. Chem Volume: 14 Issue: 28 Pages: 7720-7735
  • DOI: 10.1039/c5ob01037c
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Structure and activity relationship study of syringolin A as a potential anticancer agent. (2015)
  • Author(s): Chiba, Takuya; Matsuda, Akira; Ichikawa, Satoshi*
  • Journal Title: Bioorg. Med. Chem. Lett. Volume: 25 Issue: 21 Pages: 4872-4877
  • DOI: 10.1016/j.bmcl.2015.06.015
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Carbacaprazamycins: Chemically Stable Analogues of the Caprazamycin Nucleoside Antibiotics. (2015)
  • Author(s): Satoshi Ichikawa,* Mayumi Yamaguchi, Lee Shang Hsuan, Yuta Kato, and Akira Matsuda.
  • Journal Title: ACS Infect. Dis. Volume: １ Issue: 4 Pages: 151-156
  • DOI: 10.1021/id5000376
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Antibacterial nucleoside natural products inhibiting phospho-MurNAc-pentapeptide translocase; chemistry and structure-activity relationship. (2015)
  • Author(s): Ichikawa, Satoshi; Yamaguchi, Mayumi; Matsuda, Akira.
  • Journal Title: Current Med. Chem. Volume: 22 Issue: 34 Pages: 3951-3979
  • DOI: 10.2174/0929867322666150818103502
  • Peer Reviewed
• [Presentation] Echinomycinの合成研究 (2016)
  • Author(s): 小嶋 啓太、市川 聡
  • Organizer: 日本薬学会北海道支部143回例会
  • Place of Presentation: 札幌コンベンションセンター（北海道札幌市）
  • Year and Date: 2016-05-14
• [Presentation] 芳香族求核置換反応を利用したDNAメチル化酵素阻害剤の創製研究 (2016)
  • Author(s): 笠井由起子、佐藤浩輔、市川聡
  • Organizer: 日本薬学会第136年会 （口頭発表）
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2016-03-29
• [Presentation] エピジェネティック制御を指向した非環式C-ヌクレオシドの合成と性質 (2016)
  • Author(s): 内海翔平、佐藤浩輔、市川聡
  • Organizer: 日本薬学会第136年会 （口頭発表）
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2016-03-29
• [Presentation] Design and synthesis of simplified caprazamycin analogs. (2015)
  • Author(s): Nakaya, T.; Matsuda, A.; Ichikawa, S.
  • Organizer: PACIFICHEM, The International Chemical Congress of Pacific Basin Societies
  • Place of Presentation: Honolulu (Hawaii, USA)
  • Year and Date: 2015-12-15
• [Presentation] Design and synthesis of conformationally restricted caprazamycin analogs as antibacterial agents. (2015)
  • Author(s): Yamaguchi, M.; Ichikawa, S.; Matsuda, A.
  • Organizer: PACIFICHEM, The International Chemical Congress of Pacific Basin Societies 2015 (Poster Presentation)
  • Place of Presentation: Honolulu (Hawaii, USA)
  • Year and Date: 2015-12-15
• [Presentation] Synthetic study of plusbacin A3 (2015)
  • Author(s): Katsuyama, A.; Matsuda, A.; Ichikawa, S.
  • Organizer: PACIFICHEM, The International Chemical Congress of Pacific Basin Societies 2015 (Poster Presentation)
  • Place of Presentation: Honolulu (Hawaii, USA)
  • Year and Date: 2015-12-15
• [Presentation] Improvement of biological activities of syringolin A (2015)
  • Author(s): Chiba, T.; Matsuda, A.; Ichikawa, S.
  • Organizer: PACIFICHEM, The International Chemical Congress of Pacific Basin Societies 2015 (Poster Presentation)
  • Place of Presentation: Honolulu (Hawaii, USA)
  • Year and Date: 2015-12-15
• [Presentation] syrbactin類を基盤とした新規プロテアソーム阻害剤の開発研究 (2015)
  • Author(s): 北畑舜、千葉拓也、市川聡
  • Organizer: 第33回メディシナルケミストリーシンポジウム（口頭発表&ポスター発表）
  • Place of Presentation: 幕張国際研修センター（千葉県・幕張市）
  • Year and Date: 2015-11-26
• [Presentation] Synthetic study of plusbacin A3 (2015)
  • Author(s): Katsuyama, A.; Matsuda, A.; Ichikawa, S.
  • Organizer: 第52回ペプチド討論会( 口頭発表)
  • Place of Presentation: 中央公民館（神奈川県・平塚市）
  • Year and Date: 2015-11-16
• [Presentation] Design, synthesis and biological evaluation of 5′-C-piperidinyl-5′-aminoribosyluridines as potential antibacterial agents. (2015)
  • Author(s): Nakaya, T.; Matsuda, A.; Ichikawa, S.
  • Organizer: The 42nd International Symposium on Nucleic Acids Chemistry 2015 (Oral Presentation)
  • Place of Presentation: イーグレ姫路（兵庫県・姫路市）
  • Year and Date: 2015-09-23
• [Presentation] Syringolin類の合成と構造活性相関研究 (2015)
  • Author(s): 北畑舜、千葉拓也、市川聡
  • Organizer: 第57回天然物有機化学討論会 （ポスター発表）
  • Place of Presentation: 神奈川県民ホール（神奈川県・横浜市）
  • Year and Date: 2015-09-10
• [Presentation] Plusbacin A3の全合成研究 (2015)
  • Author(s): 勝山彬、松田彰、市川聡
  • Organizer: 第27回万有札幌シンポジウム （ポスター発表、ベストポスター賞）
  • Place of Presentation: 北海道大学（北海道・札幌市）
  • Year and Date: 2015-07-04
• [Presentation] 新規抗菌剤開発を指向したリポヌクレオシド系抗菌抗生物質の単純化研究 (2015)
  • Author(s): 山口繭美、松田彰、市川聡
  • Organizer: 第13回次世代を担う有機化学シンポジウム （口頭発表）
  • Place of Presentation: 立命館大学（滋賀県・草津市）
  • Year and Date: 2015-05-22