THE GENERATION OF ACTIVE OXYGEN SPECIES BASED ON UNIQUE REACTIVITIES OF HETEROCYCLIC N-OXIDES AND ITS APPLICATIONS
| Project/Area Number |
08672564
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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 | GIFU PHARMACEUTICAL UNIVERSITY |
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Principal Investigator |
SAKO Magoichi GIFU PHARMACEUTICAL UNIVERSITY,DEPARTMENT OF PUBLIC HEALTH PHARMACY,ASSOCIATED PROFESSOR, 薬学部, 講師 (10137060)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1996: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | PYRIMIDO [5,4-G] PTERIDINE N-OXIDE / HYDROXYL RADICAL / DNA PHOTO-CLEAVING AGENT / PYRIMIDO [3,4-D] FUROXAN / FACILE SYNTHETIC METHOD / NITRIC OXIDE / 含窒素複素環N-オキシド / 光反応特性 / DNA鎖切断 / グアノシン / 8-ヒドロキシグアノシン / 光化学的反応性 / DNA鎖切断剤 / 活性酸素種 / 気管支拡張作用 |
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| Research Abstract |
Previously, we have demonstrated that a lipophilic pyrimido [5,4-g] pteridinetetraone 5-oxide behaves as an effective oxygen-atom transfer agent to electron-rich substrates under photochemical conditions in an aprotic solvent, of which reactions proceed via a single-electron transfer process in a manner similar to that of biological monooxygenations catalyzed by cytochrome P-450, and that a hydrophilic pyrimido [5,4-g] pteridinetetraone 5-oxide generates cleanly and effectively hydroxyl radicals under the photochemical conditions in an aqueous solvent to serve as a photochemical DNA-cleaving agent.
In this research project, it has been documented that the water-soluble N-oxide preferentially degradates cytidine among the employed nucleosides including 2'-deoxycytidine, adenosines and guanosines leading to cytosine in a high yield under the photochemical conditions. This fact clearly indicates that the hydrophilic pyrimido [5,4-g] pteridinetetraone 5-oxide serves as the photochemical RNA-strand cleaving agent with a high selectivity.
Pyrimidofuroxans have been well established to be a useful synthon for the preparation of fused pyrimidines such as purines and pteridines which are compounds of ubiquitous natural occurrence and extreme biological importance. In this research project, a facile synthetic method for the pyrimidofuroxans has been accomplished. The method involves an oxidative intramolecular cyclization of appropriate 6-amino-5-nitropyrimidines with iodosylbenzene diacetate in the presence of lithium hydride. The pyrimidofuroxans generate effectively nitric oxide and related species in the presence of N-acylated cysteamines such as N-acetylcysteamine and glutathione under physiological conditions.
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Report
(3 results)
Research Products
(9 results)
