@article {271,
	title = {Design, synthesis, and biological evaluation of dual binding site acetylcholinesterase inhibitors: new disease-modifying agents for Alzheimer{\textquoteright}s disease},
	journal = {Journal of medicinal chemistry},
	volume = {48},
	year = {2005},
	month = {2005/11/17/},
	pages = {7223 - 7233},
	abstract = {New dual binding site acetylcholinesterase (AChE) inhibitors have been designed and synthesized as new potent drugs that may simultaneously alleviate cognitive deficits and behave as disease-modifying agents by inhibiting the beta-amyloid (A beta) peptide aggregation through binding to both catalytic and peripheral sites of the enzyme. Particularly, compounds 5 and 6 emerged as the most potent heterodimers reported so far, displaying IC50 values for AChE inhibition of 20 and 60 pM, respectively. More importantly, these dual AChE inhibitors inhibit the AChE-induced A beta peptide aggregation with IC50 values 1 order of magnitude lower than that of propidium, thus being the most potent derivatives with this activity reported up to date. We therefore conclude that these compounds are very promising disease-modifying agents for the treatment of Alzheimer{\textquoteright}s disease (AD).},
	keywords = {Acetylcholinesterase/chemistry; Alzheimer Disease/drug therapy; Amyloid beta-Protein/antagonists \& inhibitors/chemistry; Animals; Binding Sites; Butyrylcholinesterase/chemistry; Cattle; Cell Line, Molecular; Nootropic Agents/chemical synthesis/chemistry/toxicity; Protein Binding; Structure-Activity Relationship; Tacrine/analogs \& derivatives/chemical synthesis/chemistry/toxicity, Tumor; Cholinesterase Inhibitors/chemical synthesis/chemistry/toxicity; Dimerization; Drug Design; Erythrocytes/enzymology; Fluorometry; Humans; Models},
	author = {Munoz-Ruiz,P. and Rubio,L. and Garcia-Palomero,E. and Dorronsoro,I. and Monte-Millan,M. del and Valenzuela,R. and Usan,P. and Austria,C. de and Bartolini,M. and Andrisano,V. and A. Bidon-Chanal and M. Orozco and F. J. Luque and Medina,M. and Martinez,A.}
}
