Design, synthesis and evaluation of rivastigmine and curcumin hybrids as site-activated multitarget-directed ligands for Alzheimer's disease therapy

作者：Li, Yujie; Peng, Peng; Tang, Li; Hu, Yunzhen; Hu, Yongzhou; Sheng, Rong^*

来源：Bioorganic & Medicinal Chemistry, 2014, 22(17): 4717-4725.

DOI：10.1016/j.bmc.2014.07.009

• Multitarget-directed ligands
• AChE/BuChE inhibitor
• Radical scavenger
• Metal chelator
• A beta self-aggregation inhibitor

A series of novel 2-methoxy-phenyl dimethyl-carbamate derivatives were designed, synthesized and evaluated as site-activated MTDLs based on rivastigmine and curcumin. Most of them exhibited good to excellent AChE and BuChE inhibitory activities with sub-micromolar IC50 values. Among all the compounds, 6a demonstrated the most potent AChE inhibition with IC50 value of 0.097 mu M, which is about 20-fold than that of rivastigmine. In addition, the three selected compounds 5a, 6a and 6e demonstrated inhibitory activity against A beta self-aggregation similar to cucurmin in TEM assay, which is obviously different from the weak activity of rivastigmine. Moreover, the hydrolysate of 6a (compound 7) also showed potent ABTS(center dot+) scavenging and moderate copper ion chelating activity in vitro.

• 出版日期2014-9-1
• 单位浙江大学