2001 Fiscal Year Final Research Report Summary
Development of the Selective NOS Inhibitors Based on Novel Reaction Mechanism
| Project/Area Number |
12672063
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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 |
Chemical pharmacy
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| Research Institution | SHOWA UNIVERSITY |
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Principal Investigator |
OHSAWA Akio SHOWA UNIVERSITY SCHOOL OF PHAMACEUTICAL SCIENCES PROFESSOT, 薬学部, 教授 (00102369)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAZAKI Michiko SHOWA UNITV SCHOOL OF PHAM, Sci, ASSISTANT, 薬学部, 助手 (00266165)
NAGATA Kazuhiro SHOWA UNITV SCHOOL OF PHAM, Sci, ASSOIATE LECTURER, 薬学部, 講師 (20208010)
ITOH Takashi SHOWA UNITV SCHOOL OF PHAM, Sci, ASSOIATE PROFESSOR, 薬学部, 助教授 (40159885)
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| Project Period (FY) |
2000 – 2001
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| Keywords | nitvic oxide / azaaromatic / N-amino compound / NO scavenger / NOS inhibitor |
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| Research Abstract |
Although nitric oxide (NO) plays a variety of roles in biological systems, formation of NO in high concentration causes cytotoxicity. Thus, it is necessary to develop chemicals which quench NO only when NO is produced excessively. For developing such chemicals, we have investigated the reaction of NO with various heterocyclic compounds and found that N-aminopyridinium perchlorate reacted with NO rapidly even in water and that NO was transformed to the form of N_<2O>. This finding suggests that NO is completely detoxified via this reaction. With this precedent in hand, we further investigated the reaction of various kinds of N-anminoazaaromatics with NO, and found most of all the compounds were good scavengers of NO. Moreover, it was found that these compounds were reacted with superoxide smoothly to quench this active oxygen species. Therefore, N-aminoazaaromatics were found to be good scavengers for both NO and superoxide, both of which play a criticai role in oxidative damage in biological systems. In addition, we also found that N-alkylazaaromatic quaternary salts functioned as activators of superoxide to oxidatively cleavage C=C double bond.
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Research Products
(4 results)
