Ning Xianling, Guo Ying, Wang Xiaowei, Ma Xiaoyan, Tian Chao, Shi Xueqi, Zhu Renzong, Cheng Can, Du Yansheng, Ma Zhizhong, Zhang Zhili, Liu Junyi
Department of Chemical Biology, School of Pharmaceutical Sciences, ‡State Key Laboratory of Natural and Biomimetic Drugs, and §Department of the Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University , Beijing 100191, China.
J Med Chem. 2014 May 22;57(10):4302-12. doi: 10.1021/jm500258v. Epub 2014 May 6.
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.
设计并合成了新型（E）-3,4-二羟基苯乙烯基芳烷基砜和亚砜作为化合物1的新类似物，它们表现出有趣的多功能神经保护作用，包括抗氧化和抗神经炎症特性。具体而言，目标化合物在清除活性自由基方面表现出优异的效力，并对包括H2O2、6-羟基多巴胺和脂多糖在内的不同类型神经元细胞中的各种毒性表现出强效作用。目标化合物的抗氧化特性比化合物1更强，而抗神经炎症特性比化合物1弱。根据血脑屏障的平行人工膜渗透测定，目标化合物比化合物1具有更高的血脑屏障（BBB）通透性。简而言之，由于抗氧化作用、稳定性和BBB通透性的提高，（E）-3,4-二羟基苯乙烯基芳烷基砜和亚砜因此可被视为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先导候选物。
