Design, Synthesis, and Biological Evaluation of (E)-3,4-Dihydroxystyryl Aralkyl Sulfones and Sulfoxides as Novel Multifunctional Neuroprotective Agents
Design, Synthesis, and Biological Evaluation of (E)-3,4-Dihydroxystyryl Aralkyl Sulfones and Sulfoxides as Novel Multifunctional Neuroprotective Agents
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作为新型多功能神经保护剂的 (E)-3,4-二羟基苯乙烯基芳烷基砜和亚砜的设计、合成和生物学评价
DOI：
10.1021/jm500258v
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发表时间：
2014-05-22
影响因子：
7.3
通讯作者：
Liu, Junyi
中科院分区：
文献类型：
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作者：
Ning, Xianling;Guo, Ying;Liu, Junyi
设计并合成了新的（E）-3，4-二羟基苯乙烯基芳烷基砜和亚砜作为1的新类似物，其显示出有趣的多功能神经保护作用，包括抗氧化和抗神经炎症性质。具体而言，目标化合物在清除反应性自由基方面显示出优异的效力，并在不同类型的神经元细胞中表现出对各种毒性（包括H2 O2、6-羟基多巴胺和脂多糖）的有效作用。目标化合物的抗氧化性能比1更强，而抗神经炎症性能不如1。根据血脑屏障的平行人工膜渗透测定，目标化合物具有大于1的血脑屏障（BBB）渗透性。简而言之，由于抗氧化作用、稳定性和BBB通透性的改善，（E）-3，4-二羟基苯乙烯基芳烷基砜和亚砜因此可以被认为是潜在的多功能神经保护剂，并作为治疗神经退行性疾病的新的主要候选物。
Novel (E)-3,4-dihydroxystyryl aralkyl sulfones and sulfoxides were designed and synthesized as new analogues of 1, which showed interesting multifunctional neuroprotective effects, including antioxidative and antineuroinflammatory properties. Specifically, target compounds display excellent potency in scavenging reactive free radicals and demonstrate potent effects against various kinds of toxicities, including H2O2, 6-hydroxydopamine, and lipopolysaccharide in different types of neuronal cells. The antioxidative properties of the target compounds are more potent than that of 1, and the antineuroinflammatory properties are less strong than that of 1. According to the parallel artificial membrane permeation assay for the blood brain barrier, target compounds possess greater blood brain barrier (BBB) permeability than 1. In short, due to improvement of the antioxidative effect, stability, and BBB permeability, (E)-3,4-dihydroxystyryl aralkyl sulfones and sulfoxides can thus be considered as potential multifunctional neuroprotective agents and serve as new lead candidates in the treatment of neurodegenerative diseases.