| Project/Area Number |
62570931
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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 | Tokyo University of Information Sciences (1988)
Chiba University (1987) |
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Principal Investigator |
MAEBAYASHI Yukio Tokyo University of Information Sciences, 経営情報学部, 助教授 (00111435)
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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 |
¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1988: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1987: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Monoamine oxidase (MAO) inhibitor / Fungal metabolites / Kinetic study / Emericella navahoensis / Emericella navahoensis / Talaromyces luteus / モノアミン酸化酵素(MAO) / 阻害物質 / Emericella narahoensis / Enericella navrhoensis |
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| Research Abstract |
During a survey of monoamine oxidase(MAO) inhibitors of fungi, 220 strains of 140 species, norsolorinic acid(NSA) from Emericellla navahoensis and a new compound, tentatively named TL-1 from Talaromyces luteus were isolated as MAO inhibitors. The IC_<50>of NSA and TL-1 to MAOo were found to be 1.1 x 10^<-7> g/ml and 2.3 x 10^<-6> g/ml, respectively. When the activities of MAO-A and MAO-B in mouse brain, heart and liver homogenate were measured in the presence of NSA or TL-1. NSA and TL-1 more potently inhibited MAO-B than MAO-A. The lineweaver-Burk plots of inhibition suggested that inhibition pattern of NSA in above organs were various. On the other hand, TL-1 showed only mixed-type inhibition of MAO. The preincubation of mouse liver homogenate with NSA or TL-1 suggested that NSA inhibited MAO irreversibly and TL-1 inhibited MAO reversibly.
As NSA ontains an anthraquinone skeleton, the inhibitory potencies towards MAO of 16 fungal anthraquinones and 3 derivatives were examined. The results suggested that the presence of an anthraquinone skeleton and a side chain of six carbons with a conjugated electron system at the -position would be required for inhibitory potency. Among six TL-1 related compounds, TL-1-monoacetate and-diacetate inhibited the enzyme efficiently. TL-1 derivative with hybrogenated side chain and sclerotiorin had no effect. Azaphillon ring system like TL-1 and side chain with conjugated souble bonds would be required for inhibitory potency. It was thus domonstrated that NSA and TL-1 are new type potent inhibitor of MAO-B.
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