Institute of Drug Synthesis and Pharmaceutical Process, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Bioorg Med Chem. 2012 May 1;20(9):3038-48. doi: 10.1016/j.bmc.2012.02.059. Epub 2012 Mar 10.
A series of berberine-phenyl-benzoheterocyclic (26-29) and tacrine-phenyl-benzoheterocyclic hybrids (44-46) were synthesised and evaluated as multifunctional anti-Alzheimer's disease agents. Compound 44b, tacrine linked with phenyl-benzothiazole by 3-carbon spacers, was the most potent AChE inhibitor with an IC(50) value of 0.017 μM. This compound demonstrated similar Aβ aggregation inhibitory activity with cucurmin (51.8% vs 52.1% at 20 μM, respectively), indicating that this hybrid is an excellent multifunctional drug candidate for AD.
一系列小檗碱-苯并杂环（26-29）和他克林-苯并杂环杂合体（44-46）被合成并评估为多功能抗阿尔茨海默病药物。化合物 44b，通过 3-碳间隔基连接苯并噻唑的他克林，是最有效的乙酰胆碱酯酶抑制剂，IC（50）值为 0.017μM。该化合物在 20μM 时对 Aβ 聚集的抑制活性与姜黄素相似（分别为 51.8%和 52.1%），表明该杂合体是一种用于 AD 的优秀多功能药物候选物。
