Suzumura K, Yasuhara M, Tanaka K, Odawara A, Narita H, Suzuki T
Discovery Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
Chem Pharm Bull (Tokyo). 1999 Jul;47(7):1010-2. doi: 10.1248/cpb.47.1010.
We investigated the in vitro hydroxyl radical scavenging activity of fluvastatin, a 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitor. Fluvastatin showed hydroxyl radical scavenging activity as potent as that of dimethylthiourea and alpha-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 pravastatin 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.
我们研究了氟伐他汀（一种3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂）的体外羟自由基清除活性。氟伐他汀表现出的羟自由基清除活性与二甲基硫脲和α-生育酚相当，二甲基硫脲和α-生育酚分别是著名的羟自由基清除剂和天然抗氧化剂。由于在其他HMG-CoA还原酶抑制剂（如普伐他汀和辛伐他汀）中未观察到这种效应，氟伐他汀对羟自由基的清除作用并非HMG-CoA还原酶抑制剂的共同特性，而是源自氟伐他汀独特的化学结构。我们还测定了氟伐他汀人体代谢产物的羟自由基清除活性。所有具有氟苯基吲哚部分的测试代谢产物均表现出活性。其中，在吲哚部分带有酚羟基的代谢产物表现出比氟伐他汀更强的作用。我们认为氟伐他汀的氟苯基吲哚部分对活性的表现很重要，并且酚羟基增强了效力。
