| Project/Area Number |
62570946
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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 |
Chemical pharmacy
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| Research Institution | Nagoya City University |
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Principal Investigator |
SAKAKIBARA Jinsaku Faculty of pharmaceutical Sciences, Nagoya City University, 薬学部, 教授 (70080182)
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| Co-Investigator(Kenkyū-buntansha) |
NAGAI Shin-ichi Faculty of Pharmaceutical Sciences, Nagoya City University, 薬学部, 助手 (40080212)
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| Project Period (FY) |
1987 – 1988
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1988: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1987: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | Proscillaridin / 1,4-Cycloaddition / Inhibitory activity of Na^+,K^+-ATPase / Chemical modification of monensin / NaBr complex / 擬環状構造 / ラクタム / ディールスアルダー反応 / van der Waals volume / Na^+,K^+,ーATPase / モネンシルアミノ酸 / ^<23>NaーNMR / カチオン捕捉能 / 化学修飾 / ナトリウム・カリウムATPase / モルモット乳頭筋 / ファンデァワールス分子容積 / モネンシン / ナトリウムイオン輸送能 / 核磁気共鳴法 |
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| Research Abstract |
As an extension of our continuing program directed towards the further development of new proscillaridin analogs with a lower risk of toxicity, we undertook the chemical transformation of the lactone ring, such as 1, 4-cycloaddition with active acetylene or lactonization with alkylamines, together with the chemical modification of monensin, which increases the intracellular Na ions as well as proscillaridin.
The biological activities of proscillaridin analogs were evaluated by measurement of the enzyme inhibitory activity (pIC_<50>) of a Na^+, K^+-adenosine triphosphatase preparetion from dog kidney. New compounds were generally less potent than proscillaridin, whereas a few of lactams or 1, 4-cycloadduct showed moderately potent activity.
An X-ray crystallographic study on NaBr complexes of monensins, modified with optically active amino acids, clarified that their pseudocyclic conformations differed from that of the corresponding monensin NaBr complex.
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