Naslov
Design and evaluation of selective butyrylcholinesterase inhibitors based on Cinchona alkaloid scaffold

Autori
Bosak, Anita ; Ramić, Alma ; Šmidlehner, Tamara ; Hrenar, Tomica ; Primožič, Ines ; Kovarik, Zrinka

Izvornik
PLoS One (1932-6203) (2018); E0205193, 11

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
cinchonine, cinchonidine, selectivity, stereoselectivity, inhibition constants

Sažetak
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 K(I) 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

Izvorni jezik
Engleski

Znanstvena područja
Kemija

POVEZANOST RADA