Mechanism of Antioxidative Activity of Fluvastatin-Determination of the Active Position

• Published in: Chemical & pharmaceutical bulletin Vol. 48; no. 2; pp. 235 - 237
• Main Authors: NAKAMURA, Takashi, NISHI, Hiroyuki, KOKUSENYA, Yoshio, HIROTA, Kenichi, MIURA, Yozo
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 01.02.2000; Maruzen; Japan Science and Technology Agency
• Subjects: 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor; Anticholesteremic Agents - chemistry; Anticholesteremic Agents - pharmacology; Antioxidants - chemistry; Antioxidants - pharmacology; antioxidative activity; Biological and medical sciences; Chromatography, Liquid; Cyclic N-Oxides; Esters - chemistry; Fatty Acids, Monounsaturated - chemistry; Fatty Acids, Monounsaturated - pharmacology; Fluvastatin; Free Radicals; General and cellular metabolism. Vitamins; Hydrogen - chemistry; hydrogen-atom abstration; Indicators and Reagents; Indoles - chemistry; Indoles - pharmacology; Magnetic Resonance Spectroscopy; Medical sciences; Pharmacology. Drug treatments; Spectrophotometry, Ultraviolet; Spin Labels; Spin Trapping; Diol; Alkoxyl; Active site; Alcohol; Antioxidant; Spin trapping; Allylic compound; Fluvastatin; Hydroxyacid; Organic free radical; Indole derivatives; Mechanism of action; Antilipemic agent
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.48.235

In order to clarify the mechanism of action for the antioxidative activity of fluvastatin sodium (FLV, (±)-sodium (3RS, 5RS, 6E)-7-[3-(4-fluorophenyl)-1-(1-methylethyl)-1H-indol-2-yl]-3, 5-dihydroxy-6-heptanoate) and its derivatives, reaction of the corresponding methyl ester of FLV with di-tert-butyl diperoxyxalate was examined, and the corresponding keto derivative was isolated from the reaction mixture. On the basis of this result, it was concluded that the active site is the allylic carbon conjugated with the indole ring.