Chemical Biology & Drug Design 2015-11-01

Design, synthesis, and biological evaluation of scutellarein carbamate derivatives as potential multifunctional agents for the treatment of Alzheimer's disease.

Zhi-Pei Sang, Xiao-Ming Qiang, Yan Li, Bei Wu, Hui Zhang, Ming-Gao Zhao, Yong Deng

Index: Chem. Biol. Drug Des. 86 , 1168-77, (2015)

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Abstract

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 IC50 values of 1.2 ± 0.03 μm and 22.1 ± 0.15 μm, 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. © 2015 John Wiley & Sons A/S.