期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 177, 期 -, 页码 198-211出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2019.05.055
关键词
Alzheimer's disease; Rutacecarpine; Multitarget-directed ligands; Cholinesterases; Docking study; Drug-likeness prediction
资金
- China Postdoctoral Science Foundation [2015M571916]
- National Nature Science Foundation of China [81302701]
A series of 3-amino-substituted rutacecarpine derivatives were synthesized to identify novel multitarget-directed ligands (MTDLs) for the treatment of Alzheimer's disease (AD). Biological evaluation showed that most of the synthesized compounds inhibited butyrylcholinesterase (BuChE) and exerted antioxidant effects. Among the synthesized compounds, 6n was subjected to further biological evaluation. Lineweaver-Burk plotting and molecular modeling illustrated that 6n bound simultaneously to the peripheral anionic site (PAS) and catalytic sites (CAS) of BuChE. Furthermore, 6n modulated A beta aggregation; chelated biometals; presented good absorption, distribution, metabolism, excretion, and toxicity properties; and showed remarkable neuroprotective activity. Previous research has shown that the optimized compound 6n has considerable potential for development as an MTDL for the treatment of AD. (C) 2019 Elsevier Masson SAS. All rights reserved.
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