Computationally Designed Sesamol Derivatives Proposed as Potent Antioxidants
Computationally Designed Sesamol Derivatives Proposed as Potent Antioxidants
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DOI：
10.1021/acsomega.0c00898
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发表时间：
2020-04-28
期刊：
影响因子：
4.1
通讯作者：
Galano, Annia
中科院分区：
文献类型：
--
作者：
Castro-Gonzalez, Laura M.;Raul Alvarez-Idaboy, Juan;Galano, Annia
氧化应激已被认为在帕金森病和阿尔茨海默病等多种疾病中发挥着重要作用，这证明了抗氧化剂在改善这些健康疾病的有害影响方面具有有益作用。特别是芝麻酚，由于其抗氧化特性，已被研究用于治疗多种疾病。本文报道了新芝麻酚衍生物的合理计算设计。它们是通过在芝麻酚分子框架的三个不同位置添加四个官能团（-OH、-NH2、-COOH 和 -SH）而构建的。总共获得了 50 种单、二和三取代化合物的衍生物。所有衍生物均经过评估并与商业神经保护药物参考集进行比较。估计的特性包括吸收、分布、代谢、排泄、毒性和合成可及性。选择和淘汰分数用于选择第一组有前途的候选人。然后使用密度泛函理论估计酸基性能和反应性指数。最终选择了四种芝麻酚衍生物，它们被认为是有效的抗氧化剂，甚至比芝麻酚和 Trolox 更好。
Oxidative stress has been recognized to play an important role in several diseases, such as Parkinson's and Alzheimer's disease, which justifies the beneficial effects of antioxidants in ameliorating the deleterious effects of these health disorders. Sesamol, in particular, has been investigated for the treatment of several conditions because of its antioxidant properties. This article reports a rational computational design of new sesamol derivatives. They were constructed by adding four functional groups (-OH, -NH2, -COOH, and -SH) in three different positions of the sesamol molecular framework. A total of 50 derivatives between mono-, di-, and trisubstituted compounds were obtained. All the derivatives were evaluated and compared with a reference set of commercial neuroprotective drugs. The estimated properties are absorption, distribution, metabolism, excretion, toxicity, and synthetic accessibility. Selection and elimination scores were used to choose a first set of promising candidates. Acid-based properties and reactivity indexes were then estimated using the density functional theory. Four sesamol derivatives were finally selected, which are hypothesized to be potent antioxidants, even better than sesamol and Trolox for that purpose.