Although experiments have long provided empirical evidence that statins can suppress various oxidation pathways, theoretical attempts to quantify the antioxidant activity of statins (read, atorvastatin ATV, the only one studied so far) are not published until last year. Extensive results reported here for pitavastatin (PVT) and derivatives include the thermodynamic antioxidant descriptors (bond dissociation enthalpy [BDE], adiabatic ionization potential [IP], proton dissociation enthalpy [PDE], proton affinity [PA], and electron transfer enthalpy [ETE]) related to the three antioxidant mechanisms (hydrogen atom transfer [HAT], stepwise electron transfer proton transfer [SETPT], sequential proton loss electron transfer [SPLET]). The particular emphasis is on the PVT's hydroxylated derivatives wherein a hydroxy group replaces a hydrogen atom either on the quinoline core (Q-hydroxylated metabolites) or on the fluorophenyl ring (F-hydroxylated metabolites). The calculations indicate that both the Q- and F-hydroxylated derivatives possess antioxidant properties superior to the parent PVT molecule. Given the fact that, to the best of the knowledge, no experimental data for the antioxidant potency of PVT and its hydroxylated derivatives exist, this is a theoretical prediction for the validation of which it is aimed hereby to stimulate companion experimental in vivo and in vitro investigations and inspire pharmacologists in further drug developments.

中文翻译：

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通过自由基清除匹伐他汀及其羟基化衍生物的抗氧化活性：旨在协助药物开发的量子化学尝试

尽管实验长期以来提供了他汀类药物可以抑制各种氧化途径的经验证据，但量化他汀类药物抗氧化活性的理论尝试（即阿托伐他汀ATV，迄今为止唯一研究的一种）直到去年才发表。这里报告的匹伐他汀 (PVT) 和衍生物的广泛结果包括热力学抗氧化剂描述符（键解离焓 [BDE]、绝热电离势 [IP]、质子解离焓 [PDE]、质子亲和力 [PA] 和电子转移焓 [ETE] ]）与三种抗氧化机制（氢原子转移[HAT]、逐步电子转移质子转移[SETPT]、连续质子损失电子转移[SPLET]）相关。特别强调的是PVT的羟基化衍生物，其中羟基取代了喹啉核心（Q-羟基化代谢物）或氟苯环（F-羟基化代谢物）上的氢原子。计算表明，Q-和F-羟基化衍生物均具有优于母体PVT分子的抗氧化性能。鉴于据所知，不存在 PVT 及其羟基化衍生物的抗氧化效力的实验数据，这是一个理论预测，旨在刺激体内和体外的配套实验进行验证。调查并激励药理学家进一步开发药物。