| Project/Area Number |
01470135
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Chemical pharmacy
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| Research Institution | Tohoku University |
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Principal Investigator |
NOZOE Shigeo Pharmaceutical Inst., Tohoku Univ., 薬学部, 教授 (50013305)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Akira Pharmaceutical Inst., research associate, 薬学部, 教務職員 (00216699)
FUSHIYA Shinji Pharmaceutical Inst., Instructor, 薬学部, 助手 (80108563)
OHTA Tomihisa Pharmaceutical Inst., Instructor, Assistant Prof., 薬学部・助手, 講師 (50108560)
KUSANO Genjiro Pharmaceutical Inst., Professor Associated Prof., 薬学部, 助教授 (90004598)
KONDO Yoshikazu Pharmaceutical Inst., Professor Associated Prof., 薬学部, 助教授 (30004584)
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| Project Period (FY) |
1989 – 1990
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| Project Status |
Completed (Fiscal Year 1990)
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| Budget Amount *help |
¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1990: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1989: ¥5,500,000 (Direct Cost: ¥5,500,000)
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| Keywords | anti-cancer / cytotoxic substances / Basidiomycetes / 5-lipoxygenase / calmodulin / glutamate / 5-リポキシゲネ-ス |
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| Research Abstract |
Research work which aimed for isolation of new medicinal active substances from the source of mushroom have been done in a period of 1989-1991. Following activities were tested in the screening. 1) Anticancer activity. 2) Calmodulin inhibitory activity. 3) 5-Lipoxygenase inhibitory acitivity. 4) Glutamine synthetase inhibitory as well as glutamate agonistic activity.
1) A substance which showed very potent cytotoxic activity against P388, L1210 and colon 26 (IC_<50>=0.004 mug/ml for P388) were isolated from the extract of Xerocomus nigromaculata (Kuroazaawatake). But this substance was found to be cytosine arabinoside (Ara-C) which is using clinically as a synthetic anticancer agent. The structural work is underinvestigation for the compounds obtained from Russula subnigricans (Nisekurohatsu).
2) Fasciculic acid A-C obtained from Naematoloma fasciculare (Nigakuritake) was found to be a potent calmodulin antagonist. Activity of fasciculic acid A against calmodulin dependent phosphodiesterase was about ten times as strong as the W-7, and was found to be specific to this enzyme.
3) Several substances which inhibit the action of 5-lipoxygenase were obtained from Boletopsis leucomelas. The structure and activity of each substances were studied.
4) Two new acromelic acid derivatives, acromelic acid C and D were isolated from extract of Clitocybe acromelalga (Dokusasako). The structure of these substances were determined. Substances which behave as glutamate antagonist and agonist have been found in the crude extract of of Amanita pantherina (Ibotengutake). Isolation and structure determination were under investigation.
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