Design, synthesis and evaluation of novel 5,6,7-trimethoxyflavone-6-chlorotacrine hybrids as potential multifunctional agents for the treatment of Alzheimer's disease
Design, synthesis and evaluation of novel 5,6,7-trimethoxyflavone-6-chlorotacrine hybrids as potential multifunctional agents for the treatment of Alzheimer's disease
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DOI：
10.1016/j.bmcl.2015.02.015
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发表时间：
2015-04-01
影响因子：
2.7
通讯作者：
Deng, Zhennan
中科院分区：
文献类型：
--
作者：
Liao, Shixian;Deng, Hui;Deng, Zhennan
设计、合成了一系列 5,6,7-三甲氧基黄酮-6-氯他克林杂合体，并作为治疗阿尔茨海默病 (AD) 的多功能药物进行了评估。结果表明，目标化合物表现出良好的乙酰胆碱酯酶（AChE）抑制效力，对AChE的选择性高于丁酰胆碱酯酶（BuChE），潜在的抗氧化活性以及对自诱导β-淀粉样肽（Aβ）聚集的显着抑制效力。特别是，化合物14c具有最强的AChE抑制活性，IC50值为12.8 nM，有效抑制自身诱导的A beta(1-42)聚集，在25 mu M时抑制率为33.8%。此外，化合物14c还充当抗氧化剂和神经保护剂。此外，14c 在体外可以穿过血脑屏障 (BBB)。结果表明，化合物 14c 可能是治疗 AD 的潜在多功能候选药物。 (C) 2015 Elsevier Ltd. 保留所有权利。
A series of 5,6,7-trimethoxyflavone-6-chlorotacrine hybrids were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease (AD). The results showed that the target compounds exhibited good acetylcholinesterase (AChE) inhibitory potencies, high selectivity toward AChE over butyrylcholinesterase (BuChE), potential antioxidant activities and significant inhibitory potencies of self-induced beta-amyloid peptide (A beta) aggregation. In particular, compound 14c had the strongest AChE inhibitory activity with IC50 value of 12.8 nM, potent inhibition of self-induced A beta(1-42) aggregation with inhibition ratio of 33.8% at 25 mu M. Moreover, compound 14c acted as an antioxidant, as well as a neuroprotectant. Furthermore, 14c could cross the blood-brain barrier (BBB) in vitro. The results showed that compound 14c might be a potential multifunctional candidate for the treatment of AD. (C) 2015 Elsevier Ltd. All rights reserved.