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7055240 
Journal Article 
Design, synthesis and biological evaluation of novel donepezil-coumarin hybrids as multi-target agents for the treatment of Alzheimer's disease 
Venerando, A; Cesaro, L; Marin, O; Donella-Deana, A; Xie, S; Lan, J; Wang, X; Wang, Z; Jiang, N; Li, Fan; Wu, J; Wang, Jin; Kong, LYi; , 
2016 
Yes 
Bioorganic & Medicinal Chemistry
ISSN: 0968-0896
EISSN: 1464-3391 
PERGAMON-ELSEVIER SCIENCE LTD 
OXFORD 
24 
7 
1528-1539 
English 
26917219 
WOS:000371772300013 
Combining N-benzylpiperidine moiety of donepezil and coumarin into in a single molecule, novel hybrids with ChE and MAO-B inhibitory activity were designed and synthesized. The biological screening results indicated that most of compounds displayed potent inhibitory activity for AChE and BuChE, and clearly selective inhibition to MAO-B. Of these compounds, 5m was the most potent inhibitor for eeAChE and eqBuChE (0.87 mu M and 0.93 mu M, respectively), and it was also a good and balanced inhibitor to hChEs and hMAO-B (1.37 mu M for hAChE; 1.98 mu M for hBuChE; 2.62 mu M for hMAO-B). Molecular modeling and kinetic studies revealed that 5m was a mixed-type inhibitor, which bond simultaneously to CAS, PAS and mid-gorge site of AChE, and it was also a competitive inhibitor, which occupied the active site of MAO-B. In addition, 5m showed good ability to cross the BBB and had no toxicity on SH-SY5Y neuroblastoma cells. Collectively, all these results suggested that 5m might be a promising multi-target lead candidate worthy of further pursuit. (C) 2016 Elsevier Ltd. All rights reserved.