Artículo
Tacrine-sugar mimetic conjugates as enhanced cholinesterase inhibitors
Autor/es | Oliveira de Santana, Quelli Larissa
Santos Evangelista, Tereza C. Imhof, Petra Ferreira, Sabrina Baptista Fernández-Bolaños Guzmán, José María Sydnes, Magne O. López López, Óscar Lindback, Emil |
Departamento | Universidad de Sevilla. Departamento de Química orgánica |
Fecha de publicación | 2021-03-14 |
Fecha de depósito | 2024-02-06 |
Publicado en |
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Resumen | We have used the Cu(i)-catalyzed azide-alkyne Huisgen cycloaddition reaction to obtain two families of bivalent heterodimers where tacrine is connected to an azasugar or iminosugar, respectively,vialinkers of variable ... We have used the Cu(i)-catalyzed azide-alkyne Huisgen cycloaddition reaction to obtain two families of bivalent heterodimers where tacrine is connected to an azasugar or iminosugar, respectively,vialinkers of variable length. The heterodimers were investigated as cholinesterase inhibitors and it was found that their activity increased with the length of the linker. Two of the heterodimers were significantly stronger acetylcholinesterase inhibitors than the monomeric tacrine. Molecular modelling indicated that the longer heterodimers fitted better into the active gorge of acetylcholinesterase than the shorter counterparts and the former provided more efficient simultaneous interaction with the tryptophan residues in the catalytic anionic binding site (CAS) and the peripheral anionic binding site (PAS). |
Agencias financiadoras | Dirección General de Investigación (DGI). España Junta de Andalucía |
Identificador del proyecto | CTQ2016-78703-P
FQM134 |
Cita | Oliveira de Santana, Q.L., Santos Evangelista, T.C., Imhof, P., Ferreira, S.B., Fernández-Bolaños Guzmán, J.M., Sydnes, M.O.,...,Lindback, E. (2021). Tacrine-sugar mimetic conjugates as enhanced cholinesterase inhibitors. Organic and Biomolecular Chemistry, 19 (10), 2322-2337. https://doi.org/10.1039/d0ob02588g. |
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