Artículo
A hybrid of 1-deoxynojirimycin and benzotriazole induces preferential inhibition of butyrylcholinesterase (BuChE) over acetylcholinesterase (AChE).
Autor/es | Evangelista, Tereza Cristina Santos
López López, Óscar Puerta, Adrián Fernandes, Miguel X. Ferreira, Sabrina Baptista Fernández-Bolaños Guzmán, José María Lindback, Emil |
Departamento | Universidad de Sevilla. Departamento de Química orgánica |
Fecha de publicación | 2022 |
Fecha de depósito | 2023-06-02 |
Publicado en |
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Resumen | The synthesis of four heterodimers in which the copper(I)-catalysed azide-alkyne cycloaddition wasemployed to connect a 1-deoxynojirimycin moiety with a benzotriazole scaffold is reported. The hetero-dimers were investigated ... The synthesis of four heterodimers in which the copper(I)-catalysed azide-alkyne cycloaddition wasemployed to connect a 1-deoxynojirimycin moiety with a benzotriazole scaffold is reported. The hetero-dimers were investigated as inhibitors against acetylcholinesterase (AChE) and butyrylcholinesterase(BuChE). The heterodimers displayed preferential inhibition (>9) of BuChE over AChE in the micromolarconcentration range (IC50¼7–50mM). For the most potent inhibitor of BuChE, Cornish-Bowden plots wereused, which demonstrated that it behaves as a mixed inhibitor. Modelling studies of the same inhibitordemonstrated that the benzotriazole and 1-deoxynojirimycin moiety is accommodated in the peripheralanionic site and catalytic anionic site, respectively, of AChE. The binding mode to BuChE was different asthe benzotriazole moiety is accommodated in the catalytic anionic site. |
Agencias financiadoras | Ministerio de Ciencia e Innovación (MICIN). España Agencia Estatal de Investigación. España Junta de Andalucía |
Identificador del proyecto | D2020-116460RB-I00
FQM-134 |
Cita | Evangelista, T.C.S., López López, Ó., Puerta, A., Fernandes, M.X., Ferreira, S.B., Fernández-Bolaños Guzmán, J.M. y Lindback, E. (2022). A hybrid of 1-deoxynojirimycin and benzotriazole induces preferential inhibition of butyrylcholinesterase (BuChE) over acetylcholinesterase (AChE).. Journal of Enzyme Inhibition and Medicinal Chemistry, 37 (1), 2395-2402. https://doi.org/10.1080/14756366.2022.2117912. |
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