| Project/Area Number |
10672102
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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 |
SUEYOSHI Shoko NIHS, Div.of Org., Section Chief, 有機化学部, 室長 (80171114)
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| Co-Investigator(Kenkyū-buntansha) |
MIYATA Naoki NIHS, Div.of Org., Head, 有機化学部, 部長 (50114674)
TANNO Masayuki NIHS, Div.of Org., Senior Researcher, 有機化学部, 主任研究官 (60171914)
FUKUHARA Kiyoshi NIHS, Div.of Org., Senior Researcher, 有機化学部, 主任研究官 (70189968)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Nitric Oxide / Amidoxime / Hydroxy-L-arginine / Smooth muscular relaxation action / シアノトリアゼン |
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| 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.
1. Synthesis of amidoxime derivatives as a biotransformation model compound : We synthesized several compounds having an N-hydroxyamidino group, -C(=NOH)NH_2, which is a partial structure of N^ω-hydeoxy-L-arginine (NOHA, a key intermediate in the biosynthesis of NO from L-arginine). N-Hydroxyamidines were prepared by the reaction of nitriles or cyanamides with hydroxylamine in dioxane.
2. Determination of NO generated from the NO donor : The quantity of generated NO at 25℃ was measured using the Griess-Saltzman method. The generation of NO from these compounds was about 1-3 fold higher compared with that from NOHA.
3. An examination of vasorelaxation rate by bioassay : Arterial smooth muscle relaxation was examined using rat aortic rings which were precontracted using phenylephrine in the modified Krebs buffer before being treated with the test chemicals. The vasorelaxation rate caused by the N-hydroxyamidinotriazeno derivatives surpassed than that of NOHA in accordance with their higher NO generation ability.
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