Publication Date:
2018-10-06
Description:
by Anita Bosak, Alma Ramić, Tamara Šmidlehner, Tomica Hrenar, Ines Primožič, Zrinka Kovarik 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 K i 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.
Electronic ISSN:
1932-6203
Topics:
Medicine
,
Natural Sciences in General
