INSTITUTO DE QUIMICA, FISICA DE LOS MATERIALES, MEDIOAMBIENTE Y ENERGIA
Unidad Ejecutora - UE
Structural Determinants of the Multifunctional Profile of Dual Binding Site Acetylcholinesterase Inhibitors as Anti-Alzheimer Agents
CARLES GALDEANO, ELISABET VIAYNA, PAU ARROYO, AXEL BIDON-CHANAL, J. RAMÓN BLAS, DIEGO MUÑOZ- TORRERO, AND F. JAVIER LUQUE
CURRENT PHARMACEUTICAL DESIGN.
BENTHAM SCIENCE PUBL LTD
Año: 2010 vol. 16 p. 2818 - 2818
Dual binding site acetylcholinesterase inhibitors have recently emerged as a new class of anti-Alzheimer agents with potentialto 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 Alzheimers disease (AD). The primary target of these compounds is the enzyme acetylcholinesterase (AChE). Interaction of dual binding site AChE inhibitors withAChE results in a potent inhibitory activity of AChE and AChE-induced -amyloid peptide (A ) 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 A 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.