期刊
BIOORGANIC CHEMISTRY
卷 71, 期 -, 页码 305-314出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bioorg.2017.02.016
关键词
Alzheimer's disease; Pyridoxine-Resveratrol hybrids; Mannich base derivatives; AChE inhibitors; MAO-B inhibitors; Antioxidant; Metal-chelating
资金
- Chinese National Natural Science Foundation [20872099]
- Research Fund for the Doctoral Program of Higher Education [20110181110079]
- National Science and Technology Major Project on Key New Drug Creation and Manufacturing Program [2013ZX09301304-002]
A series of pyridoxine-resveratrol hybrids Mannich base derivatives as multifunctional agents have been designed, synthesized and evaluated for cholinesterase (ChE) and monoamine oxidase (MAO) inhibitory activity. To further explore the multifunctional properties of the new derivatives, their antioxidant activities and metal-chelating properties were also tested. The results showed that most of these compounds could selectively inhibit acetylcholinesterase (AChE) and MAO-B. Among them, compounds 7d and 8b exhibited the highest potency for AChE inhibition with IC50 values of 2.11 mu M and 1.56 mu M, respectively, and compound 7e exhibited the highest MAO-B inhibition with an IC50 value of 2.68 mu M. The inhibition kinetic analysis revealed that compound 7d showed a mixed-type inhibition, binding simultaneously to the CAS and PAS of AChE. Molecular modeling study was also performed to investigate the binding mode of these hybrids with MAO-B. In addition, all target compounds displayed good antioxidant and metal-chelating properties. Taken together, these preliminary findings can be a new starting point for further development of multifunctional agents for Alzheimer's disease. (C) 2017 Elsevier Inc. All rights reserved.
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