Design, synthesis and evaluation of rivastigmine and curcumin hybrids as site-activated multitarget-directed ligands for Alzheimer's disease therapy
Design, synthesis and evaluation of rivastigmine and curcumin hybrids as site-activated multitarget-directed ligands for Alzheimer's disease therapy
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DOI：
10.1016/j.bmc.2014.07.009
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发表时间：
2014-09-01
影响因子：
3.5
通讯作者：
Sheng, Rong
中科院分区：
文献类型：
--
作者：
Li, Yujie;Peng, Peng;Sheng, Rong
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. (C) 2014 Elsevier Ltd. All rights reserved.
