@article {507,
	title = {Structural determinants of the multifunctional profile of dual binding site acetylcholinesterase inhibitors as anti-Alzheimer agents},
	journal = {Current pharmaceutical design},
	volume = {16},
	year = {2010},
	month = {2010///},
	pages = {2818 - 2836},
	abstract = {Dual binding site acetylcholinesterase inhibitors have recently emerged as a new class of anti-Alzheimer agents with potential to positively modify the course of the disease. These compounds exhibit a multifunctional pharmacological profile arising from interaction with several biological targets involved upstream and downstream in the neurodegenerative cascade of Alzheimer{\textquoteright}s disease (AD). The primary target of these compounds is the enzyme acetylcholinesterase (AChE). Interaction of dual binding site AChE inhibitors with AChE results in a potent inhibitory activity of AChE and AChE-induced beta-amyloid peptide (Abeta) aggregation. Some dual binding site AChE inhibitors take on added value a significant ability to additionally inhibit the enzymes butyrylcholinesterase and BACE-1, involved in the co-regulation of the hydrolysis of the neurotransmitter acetylcholine and in Abeta formation, respectively. The structural determinants which mediate the interaction of dual binding site AChE inhibitors with these three important enzymes for AD treatment are herein reviewed.},
	keywords = {Acetylcholinesterase/chemistry; Alzheimer Disease/drug therapy; Amyloid Precursor Protein Secretases/antagonists \& inhibitors/chemistry; Animals; Aspartic Acid Endopeptidases/antagonists \& inhibitors/chemistry; Binding Sites/drug effects; Butyrylcholinest, Molecular; Molecular Structure},
	author = {Galdeano,C. and Viayna,E. and Arroyo,P. and A. Bidon-Chanal and Blas,J. R. and Munoz-Torrero,D. and F. J. Luque}
}
