Journal
FUTURE MEDICINAL CHEMISTRY
Volume 9, Issue 10, Pages 953-963Publisher
FUTURE SCI LTD
DOI: 10.4155/fmc-2017-0039
Keywords
acetylcholinesterase inhibitors; Alzheimer's disease; amyloid aggregation; multitarget compounds; nicotinic receptors
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Funding
- University of Bologna (RFO)
- CNR Research Project on Aging
- Italian Institute of Technology
- Majlis Amanah Rakyat scholarship from the Malaysian Government
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Aim: Alzheimer pathogenesis has been associated with a network of processes working simultaneously and synergistically. Over time, much interest has been focused on cholinergic transmission and its mutual interconnections with other active players of the disease. Besides the cholinesterase mainstay, the multifaceted interplay between nicotinic receptors and amyloid is actually considered to have a central role in neuroprotection. Thus, the multitarget drug-design strategy has emerged as a chance to face the disease network. Methods: By exploiting the multitarget approach, hybrid compounds have been synthesized and studied in vitro and in silico toward selected targets of the cholinergic and amyloidogenic pathways. Results: The new molecules were able to target the cholinergic system, by joining direct nicotinic receptor stimulation to acetylcholinesterase inhibition, and to inhibit amyloid-beta aggregation. Conclusion: The compounds emerged as a suitable starting point for a further optimization process. [GRAPHICS]
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