| Project/Area Number |
12672170
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
医薬分子機能学
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| Research Institution | National Institute of Health Sciences (NIHS) |
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Principal Investigator |
TANNO Masayuki (2001) National Institute of Health Sciences, Div. of Org., Senior Researcher, 有機化学部, 主任研究官 (60171914)
末吉 祥子 (2000) 国立医薬品食品衛生研究所, 有機化学部, 室長 (80171114)
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| Co-Investigator(Kenkyū-buntansha) |
MIYATA Naoki National Institute of Health Sciences, Div. of Org., Head, 有機化学部, 部長 (50114674)
FUKUHARA Kiyoshi National Institute of Health Sciences, Div. of Org., Section Chief, 有機化学部, 室長 (70189968)
丹野 雅幸 国立医薬品食品衛生研究所, 有機化学部, 主任研究官 (60171914)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2000: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | Nitric Oxide / Hydroxyl / Nitosamine / Amidoxime / グルコースオキシダーゼ / ヒドロキシルラジカル / ニトロソアミン / DNA切断活性 |
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| Research Abstract |
Nitric oxide (NO) is an important bioregulatory molecule responsible for endothelium-derived relaxaoon. NO reacts with a superoxide radical anion which is called active oxygen to give a peroxymtnte. However, there are many points to be indistinct aboout the influence of the same active, ve oxygen species, a hydroxy radical (hydroxyl). In the purpose of clearing this, we have developed the NO generating compounds with hydroxyl releasing ability
1.Synthesis of aromatic N-nitrosamines : We synthesized several aromatic compounds having both N-nitroso and N-oxido groups. Phenylpyridylnitrosamines were prepared by nitrosation of the corespondmg amines with sodium nitrite in formic acid.
2.Synthesis of amidoximes and hydroxyguanidines : We also synthesized several compounds having an N-hydroxyamidino group which is a partial structure of N-hydroxy-L-arginine which is a key intermediate in the biosynthesis of NO from L-arginine. Amidoximes and hydroxyguanidines were prepared by the reaction of the corresponding nitrites with hydroxylamine in dioxane.
3.Determination of NO and hydroxyl : Nitrosamines generated NO and hydroxyl by light irradiation and these radicals were detected in ESR spectroscopy. The quantity of NO was measured using the Griess-Saltzman method. Amidoxime derivatives released NO when they were oxidized with Fenton reagent. In case of amidoxime N-oxide derivatives, NO was produced by the reacton with glucoseoxidase in the presence of glucose and Fe(II) under anaerobic conditions
Now synthesized compounds will be useful for the chemical and biochemical research of the action of NO with active oxygen species.
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