School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Bioorg Med Chem Lett. 2013 Dec 15;23(24):6737-42. doi: 10.1016/j.bmcl.2013.10.034. Epub 2013 Oct 29.
A series of tacrine-ebselen hybrids were synthesised and evaluated as possible multifunctional anti-Alzheimer's disease (AD) agents. Compound 6i, which is tacrine linked with 5,6-dimethoxybenzo[d][1,2]selenazol-3(2H)-one by a six-carbon spacer, was the most potent acetylcholinesterase (AChE) and butylcholinesterase (BuChE) inhibitor, with IC50 values of 2.55 and 2.80 nM, respectively. Furthermore, this compound demonstrated similar hydrogen peroxide and peroxynitrite scavenging activity as ebselen by horseradish peroxidase assay and peroxynitrite scavenging activity assay, indicating that this hybrid is a good multifunctional drug candidate for the treatment of AD.
一系列的他克林-依布硒啉杂合体被合成并评估为具有潜在多功能的抗阿尔茨海默病（AD）药物。其中化合物 6i 是通过一个六碳间隔基将他克林与 5,6-二甲氧基苯并[d][1,2]硒唑-3（2H）-酮连接起来的，是最有效的乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BuChE）抑制剂，IC50 值分别为 2.55 和 2.80 nM。此外，通过辣根过氧化物酶测定法和过氧亚硝酸盐清除活性测定法，该化合物显示出与依布硒啉相似的过氧化氢和过氧亚硝酸盐清除活性，表明该杂合体是治疗 AD 的一种良好的多功能药物候选物。
