Development of ROS (Reactive Oxygen Species) Generating Agents for Photodynamic Therapy

• Project/Area Number: 19790043
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Physical pharmacy
• Research Institution: National Institute of Radiological Sciences
• Principal Investigator: NAKANISHI Ikuo National Institute of Radiological Sciences, 重粒子医科学センター, 主任研究員 (70356137)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,630,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2007: ¥2,200,000 (Direct Cost: ¥2,200,000)
• Keywords: 癌 / 薬学 / 有機化学 / 活性酸素種 / 放射線 / ラジカル / 光線力学療法 / 反応機構 / 活性酸素

Research Abstract

低酸素状態の固形腫瘍に有効な光線力学療法剤を開発する目的で、非酸素存在下、ピリジンN-オキシド構造を有する化合物を光電子移動還元し、その活性酸素種生成反応について検討した。その結果、ニトロ基などの電子求引性置換基を有するピリジンN-オキシドの一電子還元体は比較的安定であるのに対し、無置換のピリジンN-オキシドの場合には、N-O結合が開裂してヒドロキシルラジカルを生成することがわかった。以上の知見に基づき、新規化合物の設計を行った。

Research Products

• [Journal Article] Detection of Free Radical Reactions in an Aqueous Sample Induced by Low Linear-Energy-Transfer Irradiation (2009)
  • Author(s): 松本謙一郎、岡城 彩、永田 桂、William G. DeGraff、乳井美奈子、上野恵美、中西郁夫、小澤俊彦、James B. Mitchell、Murari C. Krishna、山本晴彦、遠藤和豊、安西和紀
  • Journal Title: Biol. Pharm. Bull. 32 Pages: 542-547
  • NAID: 110007160705
  • Peer Reviewed
• [Journal Article] Intracellular and Extracellular Redox Environment Surrounding Redox-Sensitive Contrast Agents under Oxidative Atmosphere (2009)
  • Author(s): 岡城 彩、宇井伊織、Sushma Manda、中西郁夫、松本謙一郎、安西和紀、遠藤和豊
  • Journal Title: Biol. Pharm. Bull. 32 Pages: 535-541
  • NAID: 110007160706
  • Peer Reviewed
• [Journal Article] Intracellular and Extracellular Redox Environment Surrounding Redox-Sensitive Contrast Agents under Oxidative Atmosphere (2009)
  • Author(s): A. Okajo, et al.
  • Journal Title: Biol. Pharm. Bull. 32 Pages: 535-541
  • Peer Reviewed
• [Journal Article] Detection of Free Radical Reactions in an Aqueous Sample Induced by Low Linear-Energy-Transfer Irradiation (2009)
  • Author(s): K. Matsumoto, et al.
  • Journal Title: Biol. Pharm. Bull. 32 Pages: 542-547
  • Peer Reviewed
• [Journal Article] Effect of Metal Ions on the Radical-Scavenging Rates of Hydroquinones (2008)
  • Author(s): I. Nakanishi, et al.
  • Journal Title: J. Pharm. Soc. Jpn. 128 Pages: 71-71
• [Journal Article] Structure-Activity Relationship in Radical-Scavenging Reactions of Naturally-Oriented Artepillin C Derivatives (2008)
  • Author(s): I. Nakanishi, et al.
  • Journal Title: Prog. Biochem. Biophys. 35 Pages: 290-290
• [Journal Article] Free Radical Reactions in an Aqueous Sample Caused by Heavy-Ion (Carbon) Beam Irradiation (2008)
  • Author(s): K. Matsumoto, et al.
  • Journal Title: Free Radical Biol. Med. 45
  • Peer Reviewed
• [Journal Article] One-Step Hydrogen Atom Transfer in Radical-Scavenging Reactions by Artepillin C Derivatives Enhanced by Electron-Donating Groups (2008)
  • Author(s): I. Nakanishi, et al.
  • Journal Title: Free Radical Biol. Med. 45
  • Peer Reviewed
• [Journal Article] Enhanced Radical-Scavenging Activity of Naturally-Oriented Artepillin C Derivatives (2008)
  • Author(s): S. Manda, et. al.
  • Journal Title: Chem. Commun. 2008 Pages: 626-628
  • Peer Reviewed
• [Journal Article] Effect of Methyl Substitution on Antioxidative Property and Genotoxicity of Resveratrol (2008)
  • Author(s): K. Fukuhara, et. al.
  • Journal Title: Chem. Res. Toxicol. 21 Pages: 282-287
  • Peer Reviewed
• [Journal Article] Enhanced Radical-Scavenging Activity of Artepillin C Derivatives (2008)
  • Author(s): I. Nakanishi, et. al.
  • Journal Title: FASEB J. 21
• [Journal Article] Nitroxyl Radicals: Electrochemical Redox Behaviour and Structure-Activity Relationships (2007)
  • Author(s): Sushma Manda、中西郁夫、大久保 敬、薬丸晴子、松本謙一郎、小澤俊彦、伊古田暢夫、福住俊一、安西和紀
  • Journal Title: Org. Biomol. Chem. 5 Pages: 3951-3955
  • Peer Reviewed
• [Journal Article] Effect of Solvent Polarity on the One-Electron Oxidation of Cyclic Nitroxyl Radidals (2007)
  • Author(s): Sushma Manda、中西郁夫、大久保 敬、川島知憲、松本謙一郎、小澤俊彦、福住俊一、伊古田暢夫、安西和紀
  • Journal Title: Chem. Lett. 36 Pages: 914-915
  • Peer Reviewed
• [Journal Article] Effect of Solvent Polarity on the One-Electron Oxidation of Cyclic Nitroxyl Radicals (2007)
  • Author(s): S. Manda, et. al.
  • Journal Title: Chem. Lett. 36 Pages: 914-915
  • Peer Reviewed
• [Journal Article] A Long-Lived σSemiquinone Radical Anion is Formed from N-β-Alany1-5-glutathiony1-3,4-dihydroxyphenylaranine(5-S-GAD), an Insect-Derived Antibacterial Substance (2007)
  • Author(s): N. Akiyama, et. al.
  • Journal Title: J. Biochem. 142 Pages: 41-48
  • Peer Reviewed
• [Journal Article] Involvement of Electron Transfer in the Radical-Scavenging Reaction of Resveratrol (2007)
  • Author(s): I. Nakanishi, et. al.
  • Journal Title: Chem. Lett. 36 Pages: 1276-1277
  • NAID: 10019962015
  • Peer Reviewed
• [Journal Article] Nitroxyl Radicals: Electrochemical Redox Behaviour and Structure-Activity Relationships (2007)
  • Author(s): S. Manda, et. al.
  • Journal Title: Org. Biomol. Chem. 5 Pages: 3915-3955
  • Peer Reviewed
• [Journal Article] Effects of Bio-Related Metal Ions on the Radical-Scavenging Reactions by Curcumin (2007)
  • Author(s): T. Kawashima, et. al.
  • Journal Title: J. Pharm. Soc. Jpn. 127 Pages: 76-76
• [Journal Article] Electro-Transfer Mechanism in the Radical-Scavenging Reaction of Resveratrol (2007)
  • Author(s): I. Nakanishi, et. al.
  • Journal Title: Free Radical Biol. Med. 43
  • Peer Reviewed
• [Journal Article] Intramolecular Base-Accelerated Radical-Scavenging Reaction of a Planar Catechin Derivative Having a Lysine Moiety (2007)
  • Author(s): K. Fukuhara, et. al.
  • Journal Title: Free Radical Biol. Med. 43
  • Peer Reviewed
• [Journal Article] Radical-Scavenging Rates of Biosynthetic Precursors of Vitamin E and Their Acyclic Analogues (2007)
  • Author(s): I. Nakanishi, et. al.
  • Journal Title: J. Clin. Biochem. Nutr. 41 Pages: 140-140
  • Peer Reviewed
• [Journal Article] Effect of Methyl Substitution of Antioxidative Properties and Genotoxicity of Resveratrol (2007)
  • Author(s): K. Fukuhara, et. al.
  • Journal Title: J. Clin. Biochem. Nutr. 41 Pages: 155-155
  • Peer Reviewed
• [Presentation] ラジカル消去活性の増強を目的としたビタミンE誘導体の開発 (2009)
  • Author(s): 中西郁夫 ら
  • Organizer: 第20回ビタミンE研究会
  • Place of Presentation: 奈良
• [Presentation] 抗酸化物質が関与するフリーラジカル反応のメカニズム解明に体する物理化学的アプローチ (2008)
  • Author(s): 中西郁夫
  • Organizer: 第23回日本酸化ストレス学会関東支部会
  • Place of Presentation: 横浜
  • Year and Date: 2008-12-13
• [Presentation] 天然抗酸化物質の生合成前駆体およびその類縁体のラジカル消去活性 (2008)
  • Author(s): 中西郁夫ら
  • Organizer: 第8回AOB(Antioxidant Biofactor)研究会
  • Place of Presentation: 東京
  • Year and Date: 2008-06-13
• [Presentation] Free Radical Reactions in an Aqueous Sample Caused by Heavy-Ion (Carbon) Beam Irradiation (2008)
  • Author(s): 松本謙一郎、中西郁夫、遠藤和豊、安西和紀
  • Organizer: 15th Annual Meeting of the Society for Free Radial and Medicine
  • Place of Presentation: 米国インディアナポリス
• [Presentation] 電子スピン共鳴(ESR)法を用いた生体関連酸化還元反応機構の解明 (2008)
  • Author(s): 中西郁夫
  • Organizer: 第47回電子スピンサイエンス学会年会
  • Place of Presentation: 福岡
• [Presentation] Detection of Heavy-Ion Particle Radiation-Generated Free Radicals and Modification of Their Biological Effects (2008)
  • Author(s): 安西和紀、盛武 敬、松本謙一郎、中西郁夫、Kailash Manda、上野恵美
  • Organizer: A Joint Conference of 13th In Vivo EPR Spectroscopy & Imaging and 10th International EPR Spin Trapping/Spin Labeling
  • Place of Presentation: 福岡
• [Presentation] Evaluation of Antioxidative Ability of Antioxidative Food Factors by EPR Spin-Trapping, Stopped-Flow Kinetic Analysis, and Mitochondrial ROS Assay (2008)
  • Author(s): I. Nakanishi, et al.
  • Organizer: A Joint Conference of 13th In Vivo EPR Spectroscopy & Imaging and 10th International EPR Spin Trapping/Spin Labeling
  • Place of Presentation: 福岡
• [Presentation] Detection of Heavy-Ion Particles Radiation-Generated Free Radicals and Modification of Their Biological Effects (2008)
  • Author(s): K. Anzai, et al.
  • Organizer: A Joint Conference of 13th In Vivo EPR Spectroscopy & Imaging and 10th International EPR Spin Trapping/Spin Labeling
  • Place of Presentation: 福岡
• [Presentation] Analysis of Free Radical Reactions in an Aqueous Sample Caused by Heavy-Ion (Carbon) Beam Irradiation (2008)
  • Author(s): K. Matsumoto, et al.
  • Organizer: A Joint Conference of 13th In Vivo EPR Spectroscopy & Imaging and 10th International EPR Spin Trapping/Spin Labeling
  • Place of Presentation: 福岡
• [Presentation] Structure-Activity Relationship in Radical-Scavenging Reactions of Naturally-Oriented Artepillin C Derivatives (2008)
  • Author(s): I. Nakanishi, et al.
  • Organizer: XIV Biennial Meeting of the Society for Free Radial Research International
  • Place of Presentation: 北京
• [Presentation] Free Radical Reactions in an Aqueous Sample Caused by Heavy-Ion (Carbon) Beam Irradiation (2008)
  • Author(s): K. Matsumoto, et al.
  • Organizer: 15th Annual Meeting of the Society for Free Radical Biology and Medicine
  • Place of Presentation: 米国インディアナポリス
• [Presentation] One-Step Hydrogen Atom Transfer in Radical-Scavenging Reactions by Artepillin C Derivatives Enhanced by Electron-Donating Groups (2008)
  • Author(s): I. Nakanishi, et al.
  • Organizer: 15th Annual Meeting of the Society for Free Radical Biology and Medicine
  • Place of Presentation: 米国インディアナポリス
• [Presentation] Radical-Scavenging Rates of Biosynthetic Precursors of Vitamin E and Their Acyclic Analogues (2007)
  • Author(s): I. Nakanishi, et. al.
  • Organizer: International Conference on Food Factors for Health Promotion (ICoFF2007)
  • Place of Presentation: 京都
  • Year and Date: 2007-11-30
• [Presentation] Intramolecular Base-Accelerated Radical-Scavenging Reaction of a Planar Catechin Derivative Having a Lysine Moiety (2007)
  • Author(s): K. Fukuhara, et. al.
  • Organizer: 14th Annual Meeting of the Society for Free Radical Biology and Medicine
  • Place of Presentation: 米国ワシントンD.C.
  • Year and Date: 2007-11-16
• [Presentation] Electron-Transfer Mechanism in the Radical-Scavenging Reaction of Resveratrol (2007)
  • Author(s): I. Nakanishi, et. al.
  • Organizer: 14th Annual Meeting of the Society for Free Radical Biology and Medicine
  • Place of Presentation: 米国ワシントンD.C.
  • Year and Date: 2007-11-15
• [Presentation] Structure-Activity Correlation in the Scavenging Reaction of Cumylperoxyl Radical by Polyphenolic Flavones (2007)
  • Author(s): I. Nakanishi, et. al.
  • Organizer: A Joint Conference of the International Symposium on Electron Spin Science and the 46th Annual Meeting of the Society of Electron Spin Science and Technology (ISESS-SEST2007)
  • Place of Presentation: 静岡
  • Year and Date: 2007-11-08
• [Presentation] フェノール性抗酸化物質によるフリーラジカル消去反応の分子ダイナミクス (2007)
  • Author(s): 中西郁夫
  • Organizer: 第29回日本フリーラジカル学会学術集会・第31回日本過酸化脂質・フリーラジカル学会大会合同学会
  • Place of Presentation: 名古屋
  • Year and Date: 2007-06-09
• [Presentation] Electrochemical of Cyclic Nitroxyl Radicals. Solvent Effect on the One-Electron Oxidation Potentials (2007)
  • Author(s): Sushma Mandaら
  • Organizer: 第29回日本フリーラジカル学会学術集会・第31回日本過酸化脂質・フリーラジカル学会大会合同学会
  • Place of Presentation: 名古屋
  • Year and Date: 2007-06-09
• [Presentation] 天然フェノール性抗酸化物質を基本骨格にした新規抗酸化物質の開発 (2007)
  • Author(s): 中西郁夫ら
  • Organizer: 第7回AOB研究会
  • Place of Presentation: 台北
  • Year and Date: 2007-06-01
• [Presentation] Enhanced Radical-Scavenging Activity of Artepillin C Derivatives (2007)
  • Author(s): I. Nakanishi, et. al.
  • Organizer: Experimental Biology Annual Meeting 2007
  • Place of Presentation: 米国ワシントンD.C.
  • Year and Date: 2007-05-02
• [Book] 放射線科学 (2009)
  • Author(s): 中西郁夫
  • Total Pages: 3
  • Publisher: 独立行政法人 放射線医学総合研究所
• [Book] 電子スピンサイエンス (2009)
  • Author(s): 中西郁夫
  • Total Pages: 6
  • Publisher: 電子スピンサイエンス学会
• [Book] XIV Biennial Meeting of the Society for Free Radical Research International (2009)
  • Author(s): 中西郁夫、宇都義浩、大久保 敬、川島知憲、Sushma Manda、松本謙一郎、堀 均、福原 潔、奥田晴宏、伊古田暢夫、福住俊一、小澤俊彦、安西和紀
  • Total Pages: 4
  • Publisher: International Proceedings
• [Book] ビタミンE研究の進歩XIII (2009)
  • Author(s): 中西郁夫ら
  • Total Pages: 4
  • Publisher: ビタミンE研究会
• [Book] XIV Biennial Meeting of the Society for Free Radical Research International (2009)
  • Author(s): I. Nakanishi, et al.
  • Total Pages: 4
  • Publisher: International Proceedings
• [Book] 第6回AOB研究会プロシーディング (2008)
  • Author(s): 川島知憲ら
  • Total Pages: 4
  • Publisher: AOB研究会
• [Book] 電子スピンサイエンス (2007)
  • Author(s): 福原 潔、中西郁夫
  • Total Pages: 6
  • Publisher: 電子スピンサイエンス学会
• [Book] 電子スピンサイエンス (2007)
  • Author(s): 福原 潔, ら
  • Total Pages: 6
  • Publisher: 電子スピンサイエンス学会