Guzmán-López Eduardo Gabriel, Reina Miguel, Hernández-Ayala Luis Felipe, Galano Annia
Departamento de Química, Universidad Autónoma Metropolitana-Iztapalapa, Av. Ferrocarril San Rafael Atlixco 186, Col. Leyes de Reforma 1A Sección, Alcaldía Iztapalapa, Mexico City 09310, Mexico.
Departamento de Química Inorgánica y Nuclear, Facultad de Química, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico.
Antioxidants (Basel). 2023 Jun 11;12(6):1256. doi: 10.3390/antiox12061256.
Ferulic acid has numerous beneficial effects on human health, which are frequently attributed to its antioxidant behavior. In this report, many of them are reviewed, and 185 new ferulic acid derivatives are computationally designed using the CADMA-Chem protocol. Consequently, their chemical space was sampled and evaluated. To that purpose, selection and elimination scores were used, which are built from a set of descriptors accounting for ADME properties, toxicity, and synthetic accessibility. After the first screening, 12 derivatives were selected and further investigated. Their potential role as antioxidants was predicted from reactivity indexes directly related to the formal hydrogen atom transfer and the single electron transfer mechanisms. The best performing molecules were identified by comparisons with the parent molecule and two references: Trolox and α-tocopherol. Their potential as polygenic neuroprotectors was investigated through the interactions with enzymes directly related to the etiologies of Parkinson's and Alzheimer's diseases. These enzymes are acetylcholinesterase, catechol-O-methyltransferase, and monoamine oxidase B. Based on the obtained results, the most promising candidates (FA-26, FA-118, and FA-138) are proposed as multifunctional antioxidants with potential neuroprotective effects. The findings derived from this investigation are encouraging and might promote further investigations on these molecules.
阿魏酸对人体健康有诸多有益影响，这些影响通常归因于其抗氧化行为。在本报告中，对其中许多影响进行了综述，并使用CADMA-Chem协议通过计算设计了185种新的阿魏酸衍生物。因此，对它们的化学空间进行了采样和评估。为此，使用了选择和排除分数，这些分数是根据一组描述符构建的，这些描述符考虑了药物代谢动力学性质、毒性和合成可及性。经过首次筛选，选择了12种衍生物并进行了进一步研究。从与形式氢原子转移和单电子转移机制直接相关的反应性指数预测了它们作为抗氧化剂的潜在作用。通过与母体分子以及两种参考物质：Trolox和α-生育酚进行比较，确定了性能最佳的分子。通过与直接与帕金森病和阿尔茨海默病病因相关的酶相互作用，研究了它们作为多基因神经保护剂的潜力。这些酶是乙酰胆碱酯酶、儿茶酚-O-甲基转移酶和单胺氧化酶B。根据获得的结果，提出了最有前景的候选物（FA-26、FA-118和FA-138）作为具有潜在神经保护作用的多功能抗氧化剂。这项研究得出的结果令人鼓舞，可能会促进对这些分子的进一步研究。
