الفهرس 
Title : Design, synthesis and biological evaluation of novel coumarin derivatives targeting acetylcholinesterase as neuroprotective against Alzheimer’s disease
ContentsOnly 14 pages are availabe for public view
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Abstract
Alzheimer{u2019}s disease (AD) is a neurodegenerative disease characterized by loss of memory and cognitive abilities. According to cholinergic hypothesis, reduced levels of acetylcholine (ACh) is contributed significantly to the cognitive symptoms associated with AD and advanced age. Accordingly, the mainstream direction for AD therapy is slowing the breakdown of ACh by the use of acetylcholinesterase inhibitors (AChEIs). Primarily, AChEIs have been considered only as a symptomatic therapy for AD, however recent studies have suggested that AChEIs can act as a disease-modifying agents by inhibition of the amyloid cascade. Coumarin is an interesting bioactive scaffold eliciting a wide range of biological activities including anticancer, antibacterial, anti-inflammatory and anticoagulant. A structural survey of AChEIs revealed that a number of naturally occurring and synthetic coumarin analogues exhibited potent AChE inhibitory activity. Among these inhibitors AP2238 and ensaculin which have distinct scaffold with a coumarin moiety. Moreover, it has been demonstrated that AChEIs with coumarin moiety primarily interact with the peripheral anionic site (PAS) of AChE enzyme.These findings prompt medicinal chemists to design dual inhibitors of AChE by incorporating a catalytic site interacting moiety with coumarin through an appropriate linker. In this regard, the AChE inhibitory activity of the coumarin nucleus notably 7-benzyloxycoumarin derivatives was highlighted