Design and evaluation of selective butyrylcholinesterase inhibitors based on Cinchona alkaloid scaffold.
PLoS One
; 13(10): e0205193, 2018.
Article
en En
| MEDLINE
| ID: mdl-30289893
ABSTRACT
This paper describes the synthesis and anticholinesterase potency of Cinchona-based alkaloids; ten quaternary derivatives of cinchonines and their corresponding pseudo-enantiomeric cinchonidines. The quaternization of quinuclidine moiety of each compound was carried out with groups diverse in their size methyl, benzyl and differently meta- and para-substituted benzyl groups. All of the prepared compounds reversibly inhibited human butyrylcholinesterase and acetylcholinesterase with Ki constants within nanomolar to micromolar range. Five cinchonidine derivatives displayed 95-510 times higher inhibition selectivity to butyrylcholinesterase over acetylcholinesterase and four were potent butyrylcholinesterase inhibitors with Ki constants up to 100 nM, of which N-para-bromobenzyl cinchonidinium bromide can be considered a lead for further modifications and optimizations for possible use in the treatment of neurodegenerative diseases.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Butirilcolinesterasa
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Diseño de Fármacos
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Inhibidores de la Colinesterasa
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Alcaloides de Cinchona
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Enfermedades Neurodegenerativas
Límite:
Humans
Idioma:
En
Año:
2018
Tipo del documento:
Article