| Project/Area Number |
60560132
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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 |
製造化学・食品
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| Research Institution | The University of Tokyo |
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Principal Investigator |
YOSHIDA Shigeo The University of Tokyo, Assistant, 農学部, 助手 (50011987)
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| Project Period (FY) |
1985 – 1986
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1986: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1985: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | Respiratory inhibitors / NADH oxidase / Drug / 分子プローブ |
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| Research Abstract |
Structure-activity relationships of specific inhibitors for NADH oxidase in respiratory (mitochondrial) electron transport system were studied. The design of bioactive substances was considered on the structural resemblance between piericidins and rotenones. Target molecules were generally synthesized by path ways involving an unique cyclization of ethyl -(N-methoxyacetyl)aminocrotate to form the pyridine ring. The synthetic compounds are classified into three types according to their lipophilic part structures; strait side-chain (I), arylic side-chain (II) and cyclic (III) compounds. Bio-assay for those compounds was carried out by the use of mitochondria of rat liver and/or bovine heart. Among the synthetic compounds, type (I) was confirmed to be totally inactive since the branched structure like the side-chain of piericidins was thought to be essential for the activity. On the other hand, some of compounds in types (II) and (III) showed remarkable inhibition at NADH oxidase site. this fact means that we have found very effective "molecular probes" to examine the spacious size of inhibitor-binding-site in NADH oxidase. Especially the activity in type (III) has rationalized our speculation; "combination of the pyridine ring part of piericidins and the cyclic part of lipophilic functions of rotenone should cause the specific inhibition at NADH oxidation".
In conclusion of this research, it is very important to continue structure-activity studies for novel type inhibitors of NADH oxidase so that higher activity of synthetic compounds will be found in those mitochondrial bio-assay system. Furthermore, it is suggested that we should consider about in vivo activity by the use of insects and/or fungi to to develop new chemicals such as insecticides and/or fungicides.
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