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Development of the Selective NOS Inhibitors Based on Novel Reaction Mechanism

Research Project

Project/Area Number 12672063
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Chemical pharmacy
Research InstitutionSHOWA UNIVERSITY

Principal Investigator

OHSAWA Akio  SHOWA UNIVERSITY SCHOOL OF PHAMACEUTICAL SCIENCES PROFESSOT, 薬学部, 教授 (00102369)

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)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsnitvic oxide / azaaromatic / N-amino compound / NO scavenger / NOS inhibitor
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.

Report

(2 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • Research Products

    (4 results)

All Other

All Publications (4 results)

  • [Publications] A.Ohsawa., et al.: "Cleavage of S-S Bond by Nitric Oxide (NO) in the Presence of Oxygen : A Disproportionation Reaction of Two Disulfides"Chem. Pharm. Bull. 48. 1524-1528 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] A.Ohsawa., et al.: "Radical Scavenging by N-Aminoazaaromatics"Bioorg. Med. Chem. 8. 1983-1989 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] N. Tsutsumi, T. Itoh, and A. Ohsawa: "Cleveage of S-S Bond by Nitric Oxide(NO) in the Presence of Oxygen : A Didproportionation Reaction of Two Disulfides"Chem. Pharm. Bull.. 48. 1524-1528 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T. Itoh, M. Miyazawaki, H. Maeta, Y. Mtsuya, K. Nagata, and A. Ohsawa: "Radical Scavenging by N-Aminoazaaromatics."Bioorg. Med. Cham.. 8. 1983-1989 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary

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Published: 2000-04-01   Modified: 2016-04-21  

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