Development of tacrine clusters as positively cooperative systems for the inhibition of acetylcholinesterase

The synthesis of four tetra-tacrine clusters where the tacrine binding units are attached to a central scaffold via linkers of variable lengths is described. The multivalent inhibition potencies for the tacrine clusters were investigated for the inhibition of acetylcholinesterase. Two of the tacrine...

Descripción completa

Detalles Bibliográficos
Autores: Evangelista, Tereza Cristina Santos, López López, Óscar, Ferreira, Sabrina Baptista, Fernández-Bolaños Guzmán, José María, Sydnes, Magne O., Lindbäck, Emil
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/131938
Acceso en línea:https://hdl.handle.net/11441/131938
https://doi.org/10.1080/14756366.2021.1954917
Access Level:acceso abierto
Palabra clave:Acetylcholinesterase
CuAAC
multivalent interactions
multivalent inhibition potency
tacrine
Descripción
Sumario:The synthesis of four tetra-tacrine clusters where the tacrine binding units are attached to a central scaffold via linkers of variable lengths is described. The multivalent inhibition potencies for the tacrine clusters were investigated for the inhibition of acetylcholinesterase. Two of the tacrine clusters displayed a small but significant multivalent inhibition potency in which the binding affinity of each of the tacrine binding units increased up to 3.2 times when they are connected to the central scaffold.