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Design, Synthesis, and Biological Evaluation of Scutellarein Carbamate Derivatives as Potential Multifunctional Agents for the Treatment of Alzheimer's Disease
Author(s) -
Sang Zhipei,
Qiang Xiaoming,
Li Yan,
Wu Bei,
Zhang Hui,
Zhao Minggao,
Deng Yong
Publication year - 2015
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12580
Subject(s) - acetylcholinesterase , butyrylcholinesterase , chemistry , neuroprotection , pharmacology , antioxidant , tacrine , trolox , cholinesterase , in vivo , potency , aché , biochemistry , in vitro , enzyme , medicine , biology , antioxidant capacity , microbiology and biotechnology
A series of scutellarein carbamate derivatives were designed and synthesized based on the multitarget‐directed drug design strategy for treatment of Alzheimer's disease. Their acetylcholinesterase and butyrylcholinesterase inhibitory activities, antioxidant activities, metals chelation, and neuroprotective effects against hydrogen peroxide‐induced PC12 cell injury were evaluated in vitro . The preliminary results indicated that compound 7b exhibited good inhibitory potency toward AChE and BuChE with IC 50 values of 1.2 ± 0.03 μ m and 22.1 ± 0.15 μ m , respectively, possessed the strong antioxidant potency (10.3 trolox equivalents), as well as acted as a selective metal chelator and neuroprotective agent. Furthermore, 7b could improve memory impairment induced by scopolamine, ethanol, and sodium nitrite using the step‐down passive avoidance task in vivo and could remarkably decrease the activity of acetylcholinesterase in mice brain. This study indicated that 7b could be considered as a potential multitarget agent against AD.