| Project/Area Number |
12672078
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Chemical pharmacy
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| Research Institution | Kobe Pharmaceutical University |
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Principal Investigator |
IWASA Kuniko Kobe Pharmaceutical University, Pharmacy, Associate Professor, 薬学部, 助教授 (30068340)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIYAMA Yumi Kobe Pharmaceutical University, Pharmacy, Assistant, 薬学部, 助手 (30248116)
ICHIMURA Momoyo Kobe Pharmaceutical University, Pharmacy, Lecturer, 薬学部, 講師 (00175259)
MORIYASU Masataka Kobe Pharmaceutical University, Pharmacy, Professor, 薬学部, 教授 (40102107)
WATAYA Yusuke Okayama University, Pharmacy, Professor, 薬学部, 教授 (90127598)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2002: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2001: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2000: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | isoquinoline alkaloids / biological activity / structure-activity relationship / plant tissue cultures / metabolites / biotransformation / structural analysis / LC / NMR-LC / MS / イソキノリン アルカロイド / 抗酸化活性 / 発がんプロモーション抑制活性 / 構造-活性相関 / 植物組織培養細胞 / 代謝物の構造解析 / isoquinoline alkaloids / antimalarial activity / antitumor activity / antiHIV activity / antimicrobial activity / structure-activity relationships |
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| Research Abstract |
1. Biological Activity of Isoquinoline Alkaloids
(1) Cytotoxicity of the Protoberberine-Type Alkaloids
Cytotoxic activities of twenty four quaternary protoberberine alkaloids related to berberine have been evaluated using a human cancer cell line panel coupled with a drug sensitivity database. Extending the alkyl chain at position 8 or 13 strongly influenced the cytotoxic activity, that is, relative lipophilicity as well as the size of the substituent affects cytotoxicity. The highest level of activity was observed in 8- or 13-hexyl substituted derivatives of berberine.
(2) Biological Activity of Simple Isoquinoline and Benzylisoquinoline Alkaloids
Twenty-six simple isoquinolines and 21 benzylisoquinolines were tested for antimicrobial, antimalarial, cytotoxic, and anti-HIV activities. Some simple isoquinoline alkaloids significantly active in each assay, and may be useful as lead compounds for developing potential chemotherapeutic agents. A quatemary nitrogen atom of isoquinolinium type m
… More
ay contribute to enhanced potency in the first three types activities. In contrast, anti-HIV activity was found with tetrahydroisoquinoline-type salts.
(3) Fungicidal and Herbicidal Activities of Berberine Related Alkaloids
The 23 quaternary and tertiary protoberberines related to berberine were tested for in vitro and/or in vivo fungicidal and herbicidal activities. Among the compounds tested, there was some activity observed with some of only the protoberberiniumsalts, but not sufficiently strong or broad spectrum for agrochemical utility. From the structure-activity point of view, some features can be pointed out.
2. Structural Analysis of Alkaloid Metabolites in Cell Culture of Corydalis Species by LC/NMR and LC/MS
The biotransformations of 1-benzyltetrahydroisoquinolines in the cultured cells of Corydalis species were studied. Identification of metabolites was performed using LC/MS and LC/NMR techniques. These techniques enabled us to assign rapidly structures to these metabolites while avoiding the isolation of individual compounds. It was found that some metabolites were new 2, 3, 10, 11-oxygenated protoberberines. Less
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