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Synthesis and Characterization of Biologically Active NO-donors

Research Project

Project/Area Number 06672245
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field 医薬分子機能学
Research InstitutionNational Institute of Health Sciences(NIHS)

Principal Investigator

MIYATA Naoki  National Institute of Health Sciences, Div.of Org., Head, 有機化学部, 部長 (50114674)

Co-Investigator(Kenkyū-buntansha) TANNO Masayuki  National Institute of Health Sciences, Div.of Org., Senior Researcher, 有機化学部, 主任研究官 (60171914)
SUEYOSHI Shoko  National Institute of Health Sciences, Div.of Org., Section Chief, 有機化学部, 室長 (80171114)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1995: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1994: ¥1,500,000 (Direct Cost: ¥1,500,000)
KeywordsNO / Nitric Oxide / N-nitroso compound / NO-donor / N-nitroso urea / Cytotoxicity / Griess-Salzman method / ニトロソウレア / グリース反応 / ニトロシル錯体 / 細胞毒性
Research Abstract

Nitric oxide (NO) is an important bioregulatory molecule responsible for endothelium-derived relaxation and to be involved in the actions of macrophages.However, the difficulty in handling such a gaseous and labile NO causes problems with the effective and precise studies of the biological effects of NO.In these situations, we have developed an NO-releasing compound under biological conditions that is useful for the chemical and biochemical research of the action of NO.
N-Nitroso compounds were prepared by the nitrosation of the corresponding ureas or amides. Trisubstituted nitrosoureas were obtained by the reaction with N^3 -dialkylated phenylureas and sodium nitrite in formic acid.Disubstituted nitrosoureas were prepared by the nitrosation with isoamyl nitrite in chloroform.The Griess-Salzman method was applied to determine the NO generation from the N-nitroso compounds.The generated NO was changed to NO_2- in the solution of the Griess reagent in the presence of oxygen and subsequent … More ly converted to an azo compound.The synthesized N-nitroso compounds release NO and the sizes of the alkyl substituents at the ureido-N^3 nitrogen of the N-nitrosoureas influenced the ability of NO generation.When the lone pair electrons on the ureide-N^1 nitrogen conjugate with pi-electrons on the aromatic ring, the N-NO bond becomes liable and is homolitically cleaved to generate NO.Aliphatic N-nitroso compounds not having such a conjugated system could never yield NO in our experimental conditions.3,3-Dibenzyl-l-(4-tolyl)-1-nitrosourea had the best NO generating ability at room temperature.The cytotoxic tests of N-nitroso compounds using cultured L-5178 Y cells revealed that the cytotoxic action of the aromatic N-nitroso compounds on the growth inhibition was apparently good. The amount of NO genration was related to the reciprocal of the ID50 values for the N-nitroso compounds.It is revealed that N-nitrosoureas are good candidates for the biologically active NO-donors which can release in the biological conditions. Less

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report

Research Products

(17 results)

All Other

All Publications (17 results)

  • [Publications] M. Tanno: "Nitric Oxide Generation from Aromatic N-Nitrosoureas at Ambient Temperature" Chem. Pharm. Bull. ,. (submitted).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 丹野雅幸: "NO-化学と生物: NO供与剤 (NO Donor)" 化学総説. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 丹野雅幸: "一酸化窒素(NO)発生剤の研究(I): 自発発生化合物の開発とNO検出法" 磁気共鳴と医学. 7. 227-229 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 末吉祥子: "一酸化窒素(NO)発生剤の研究(II): Biotransformation モデル化合物の合成とNO発生及び平滑筋弛緩作用" 磁気共鳴と医学. 7. 230-232 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 丹野雅幸: "生体内でNOを発生する化合物" 現代化学. 227. 36-41 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] M. Tanno: "Transnitrosation by N-Aryl-N-nitrosoureas ; NO-Carring O-Nitrosoisourea" Chem. Pharm. Bull.42. 1760-1767 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Masayuki Tanno, Shoko Sueyoshi, Naoki Miyata, et al.: "Nitric oxide generation from aromatic N-nitrosoureas at ambient temperatre" Chem.Pharm.Bull.(submitted.).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Masayuki Tanno, Shoko Sueyoshi and Naoki Miyata: "Nitric oxide-chemistry and biology : NO-donors" Kagakusousetu.(in press.).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Masayuki Tanno, Shoko Sueyoshi, Naoki Miyata, et al.: "Studies of NO-donors (I) : Synthesis of NO-generating compounds and development of a simple apparatus for the NO determination." Jikikyoumeito igaku. 7. 227-229 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Masayuki Tanno, Shoko Sueyoshi Naoki Miyata, et al.: "Studies of NO-donors (II) : Synthesis of biotransformation model compounds, their NO-generating ability and the relaxation of smooth muscle." Jikikyoumeito igaku. 7. 230-232 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Masayuki Tanno and Naoki Miyata: "NO-generating compounds in biological system" Gendaikagaku. 227. 36-41 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Masayuki Tanno, Shoko Sueyoshi and Naoki Miyata: "Transnitrosation by N-aryl-N-nitrosoureas ; NO-Carrying O-nitrosoureas" Chem.Pharm.Bull.42. 1760-1767 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 丹野雅幸: "NOの化学と生物:NO供与剤(NO Donor)" 化学総説. (in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 丹野雅幸: "一酸化窒素発生剤の研究(I):自発発生化合物の開発とNO検出法" 磁気共鳴と医学. 7. 227-229 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 末吉祥子: "一酸化窒素発生剤の研究(II):Biohansformationモデル化合物の合成" 磁気共鳴と医学. 7. 230-232 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Masayuki,Tanno: "Transnitration by N-Aryl-N-nitrosoureas;NO-Carring O-Nitrosourea," Chem.Pharm.Bull.,. 42. 1760-1767 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 丹野雅幸: "生体内でNOを発生する化合物" 現代化学. 36-41 (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1994-03-31   Modified: 2016-04-21  

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