NO-donating tacrine derivatives as potential butyrylcholinesterase inhibitors with vasorelaxation activity
作者： Yao Chen , Jianfei Sun , Zhangjian Huang , Hong Liao , Sixun Peng
DOI: 10.1016/J.BMCL.2013.04.008
关键词: Pharmacology 、 Acetylcholinesterase 、 Stereochemistry 、 Active site 、 Butyrylcholinesterase 、 Binding site 、 Cholinesterase 、 Structure–activity relationship 、 Tacrine 、 In vitro 、 Chemistry 、 Organic chemistry 、 Clinical biochemistry 、 Molecular medicine 、 Biochemistry 、 Molecular biology 、 Drug discovery 、 Pharmaceutical Science
摘要: To search for potent anti-Alzheimer's disease (AD) agents with multifunctional effects, 12 NO-donating tacrine-flurbiprofen hybrid compounds (2a-l) were synthesized and biologically evaluated. It was found that all the new target showed selective butyrylcholinesterase (BuChE) inhibitory activity in vitro comparable or higher than tacrine 1a-c, released moderate amount of NO vitro. The kinetic study suggests one most active highest BuChE 2d may not only compete substrate same catalytic site (CAS) but also interact a second binding site. Furthermore, 2l exhibited significant vascular relaxation effect, which is beneficial treatment AD. All results suggest might be promising lead further research.
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