Potential therapeutic antioxidants that combine the radical scavenging ability of myricetin and the lipophilic chain of vitamin E to effectively inhibit microsomal lipid peroxidation
Potential therapeutic antioxidants that combine the radical scavenging ability of myricetin and the lipophilic chain of vitamin E to effectively inhibit microsomal lipid peroxidation
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DOI：
10.1016/j.bmc.2004.02.031
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发表时间：
2004-05-01
影响因子：
3.5
通讯作者：
Hartley, RC
中科院分区：
文献类型：
--
作者：
Bennett, CJ;Caldwell, ST;Hartley, RC
黄酮醇杨梅素与氧中心的galvinoxyl自由基反应的速度比d-α-生育酚（维生素E）快28倍，后者是生物膜中主要的脂溶性抗氧化剂。此外，每个杨梅素分子减少的自由基是维生素E的两倍。然而，杨梅素未能保护维生素E缺乏的微粒体免受脂质过氧化，如通过硫代巴比妥酸反应物质（TBARS）的形成所评估的。已经制备了新的和潜在的治疗性抗氧化剂，其将杨梅素样头部基团的自由基清除能力与类似于维生素E的亲脂链相结合。C-6-C-12烷基链连接到3，3 ′，4 ′，5 ′-四羟基黄酮或3，2 ′，4 ′，5 ′-四羟基黄酮头基的A-环上，得到亲脂性黄酮（Clog P = 4 - 10），其显著抑制微粒体制剂的铁-ADP催化氧化。头部基团的方向以及总亲脂性是抗氧化剂功效的重要决定因素。MM 2模型表明，我们最好的直链7-烷基类黄酮嵌入膜中的深度与维生素E相同。类黄酮头部基团通过羟醛缩合，然后通过Algar-Flynn-Oyamada（AFO）氧化或通过Baker-Venkataraman重排来制备。烷基尾通过Suzuki或Negishi钯催化的交叉偶联或通过由第一代Grubbs催化剂催化的交叉复分解引入，其耐受酚羟基和酮基团。(C)2004 Elsevier Ltd.保留所有权利。
The flavonol myricetin, reacts with oxygen-centred galvinoxyl radicals 28 times faster than d-alpha-tocopherol (vitamin E), the main lipid-soluble antioxidant in biological membranes. Moreover, each myricetin molecule reduces twice as many such radicals as vitamin E. However, myricetin fails to protect vitamin E-deficient microsomes from lipid peroxidation as assessed by the formation of thiobarbituric acid reactive substances (TBARS). Novel and potentially therapeutic antioxidants have been prepared that combine the radical-scavenging ability of a myricetin-like head group with a lipophilic chain similar to that of vitamin E. C-6-C-12 alkyl chains are attached to the A-ring of either a 3,3',4',5'-tetrahydroxyflavone or a 3,2',4',5'-tetrahydroxyflavone head group to give lipophilic flavonoids (Clog P = 4 to 10) that markedly inhibit iron-ADP catalysed oxidation of microsomal preparations. Orientation of the head group as well as total lipophilicity are important determinants of antioxidant efficacy. MM2 models indicate that our best straight chain 7-alkylflavonoids embed to the same depth in the membrane as vitamin E. The flavonoid head groups are prepared by aldol condensation followed by Algar-Flynn-Oyamada (AFO) oxidation or by Baker-Venkataraman re-arrangement. The alkyl tails are introduced by Suzuki or Negishi palladium-catalysed cross-coupling or by cross-metathesis catalysed by first generation Grubbs catalyst, which tolerate phenolic hydroxyl and ketone groups. (C) 2004 Elsevier Ltd. All rights reserved.