TY - JOUR
T1 - Multitarget drug design strategy in Alzheimer's disease
T2 - Focus on cholinergic transmission and amyloid-β aggregation
AU - Simoni, Elena
AU - Bartolini, Manuela
AU - Abu, Izuddin F.
AU - Blockley, Alix
AU - Gotti, Cecilia
AU - Bottegoni, Giovanni
AU - Caporaso, Roberta
AU - Bergamini, Christian
AU - Andrisano, Vincenza
AU - Cavalli, Andrea
AU - Mellor, Ian R.
AU - Minarini, Anna
AU - Rosini, Michela
PY - 2017/6/1
Y1 - 2017/6/1
N2 - 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-β aggregation. Conclusion: The compounds emerged as a suitable starting point for a further optimization process.
AB - 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-β aggregation. Conclusion: The compounds emerged as a suitable starting point for a further optimization process.
KW - acetylcholinesterase inhibitors
KW - Alzheimer's disease
KW - amyloid aggregation
KW - multitarget compounds
KW - nicotinic receptors
UR - http://www.scopus.com/inward/record.url?scp=85021275057&partnerID=8YFLogxK
U2 - 10.4155/fmc-2017-0039
DO - 10.4155/fmc-2017-0039
M3 - Article
C2 - 28632446
AN - SCOPUS:85021275057
SN - 1756-8919
VL - 9
SP - 953
EP - 963
JO - Future Medicinal Chemistry
JF - Future Medicinal Chemistry
IS - 10
ER -