An in Vitro Study of the Hydroxyl Radical Scavengin Property of Fluvastatin, and HMG-CoA Reductase Inhibitor

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概要

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• We investigated the in vitro hydroxyl radical scavengig activity of fluvastatin, a 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitor. Fluvastain showed hydroxyl redical scavenging activity as potent as that of dimethylthiourea and α-tocopherol, which are well-known respectively, as a hydroxyl radical scavenger and a natural antioxidant. Since this effect was not observed in other HMG-CoA reductase inhibitors, such as pravastain and simvastatin, the scavenging effect of fluvastatin on hydroxyl radicals would not be a common property of HMG-CoA reductase inhibitors, but is derived from the unique chemical structure of fluvastatin. The hydroxyl radical scavenging activities of human metabolites of fluvastatin were also determined. All the tested metabolites possessing the fluorophenyl indole moiety showed activity. Among them, the metabolites which possess a phenolic hydroxyl group on the indole moiety showed stronger effects than that of fluvastatin. We suggest that the fluorophenyl indole moiety of fluvastatin is important for manifestation of the activity and that the phenolic hydroxyl group enhances the potency.

• 公益社団法人日本薬学会の論文
• 1999-07-15

著者

• 斎藤 徹

  Faculty Of Pharmaceutical Sciences Kanazawa University

• Tanaka K

  Department Of Molecular Engineering Graduate School Of Engineering Kyoto University

• Suzuki T

  Drug Discovery Research Laboratory Sanwa Kagaku Kenkyusho Co. Ltd.

• Narita H

  Discovery Research Laboratory Tanabe Seiyaku Co. Ltd.

• Tanaka Ken-ichiro

  Faculty Of Pharmaceutical Sciences Okayama University

• 鈴木 徳治

  千葉大 薬

• Suzuki T

  Laboratory Of Biopharmaceutics Faculty Of Pharmaceutical Sciences Chiba University

• Saito T

  Research And Development Headquarters Hokurikit Seiyaku Co. Ltd.

• Saito Takako

  Research And Development Laboratories Maruho Co. Ltd.

• Suzuki Toshikazu

  Discovery Research Laboratory Tanabe Seiyaku Co. Ltd.

• Tanaka Katsuyuki

  Dept. Biol. Sci. Fac. Sci. Hiroshima Univ.

• SUZUMURA Kuniharu

  Descovery Research Laboratory, Tanabe Seiyaku Co., Ltd.,

• YASUHARA Mikiko

  Descovery Research Laboratory, Tanabe Seiyaku Co., Ltd.,

• TANAKA Keiko

  Descovery Research Laboratory, Tanabe Seiyaku Co., Ltd.,

• ODAWARA Akio

  Descovery Research Laboratory, Tanabe Seiyaku Co., Ltd.,

• NARITA Hiroshi

  Descovery Research Laboratory, Tanabe Seiyaku Co., Ltd.,

• SUZUKI Toshikazu

  Descovery Research Laboratory, Tanabe Seiyaku Co., Ltd.,

• Odawara A

  Tanabe Seiyaku Co. Ltd. Saitama Jpn

• Tanaka K

  Dept. Biol. Sci. Fac. Sci. Hiroshima Univ.

• Suzuki T

  Research Unit Of Pharmaceutics College Of Pharmacy Nihon University

• Sugihara T

  Faculty Of Pharmaceutical Sciences Tokushima Bunri University

• Saito T

  Research And Development Laboratories Maruho Co. Ltd.

• Yasuhara M

  Discovery Research Laboratory Tanabe Seiyaku Co. Ltd.

• Suzumura Kuniharu

  Discovery Research Laboratory Tanabe Seiyaku Co. Ltd.

• Suzumura Kuniharu

  Faculty Of Pharmaceutical Sciences Chiba University

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