1995 Fiscal Year Final Research Report Summary
Synthesis and Characterization of Biologically Active NO-donors
| Project/Area Number |
06672245
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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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 |
MIYATA Naoki National Institute of Health Sciences, Div.of Org., Head, 有機化学部, 部長 (50114674)
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| 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)
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| Project Period (FY) |
1994 – 1995
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| Keywords | NO / Nitric Oxide / N-nitroso compound / NO-donor / N-nitroso urea / Cytotoxicity / Griess-Salzman method |
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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.
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
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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
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Research Products
(12 results)
