Design,Synthesis, and Biological Evaluation of Scutellarein Carbamate Derivatives as Potential Multifunctional Agents for the Treatment of Alzheimer's Disease |
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| Authors: | Zhi‐pei Sang Xiao‐ming Qiang Yan Li Bei Wu Hui Zhang Ming‐gao Zhao Yong Deng |
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| Institution: | 1. Department of Medicinal Chemistry, Key Laboratory of Drug Targeting and Drug Delivery System of the Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu, China;2. Department of Pharmacology, Fourth Military Medical University, Xi'an, China |
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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. |
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| Keywords: | AChE inhibitors Alzheimer's disease antioxidant metal chelator neuroprotective effects scutellarein carbamates synthesis |
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