A design strategy to convert a dual-binding site AChE inhibitor into triple functional compounds with promising in vitro profile against multifactorial syndromes, such as Alzheimer's disease, is proposed. The lead compound bis(7)-tacrine ( 2) was properly modified to confer to the new molecules the ability of chelating metals, involved in the neurodegenerative process. The multifunctional compounds show activity against human AChE, are able to inhibit the AChE-induced amyloid-beta aggregation, and chelate metals, such as iron and copper
Bolognesi ML, Cavalli A, Valgimigli L, Bartolini M, Rosini M, Andrisano V, et al. (2007). Multi-Target-Directed Drug Design Strategy: From a Dual Binding Site Acetylcholinesterase Inhibitor to a Trifunctional Compound against Alzheimer's Disease. JOURNAL OF MEDICINAL CHEMISTRY, 50, 6446-6449 [10.1021/jm701225u].
Multi-Target-Directed Drug Design Strategy: From a Dual Binding Site Acetylcholinesterase Inhibitor to a Trifunctional Compound against Alzheimer's Disease
BOLOGNESI, MARIA LAURA;CAVALLI, ANDREA;VALGIMIGLI, LUCA;BARTOLINI, MANUELA;ROSINI, MICHELA;ANDRISANO, VINCENZA;RECANATINI, MAURIZIO;MELCHIORRE, CARLO
2007
Abstract
A design strategy to convert a dual-binding site AChE inhibitor into triple functional compounds with promising in vitro profile against multifactorial syndromes, such as Alzheimer's disease, is proposed. The lead compound bis(7)-tacrine ( 2) was properly modified to confer to the new molecules the ability of chelating metals, involved in the neurodegenerative process. The multifunctional compounds show activity against human AChE, are able to inhibit the AChE-induced amyloid-beta aggregation, and chelate metals, such as iron and copperI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
