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

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.

SUBMITTER: Bosak A

PROVIDER: S-EPMC6173406 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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

Bosak Anita A Ramić Alma A Šmidlehner Tamara T Hrenar Tomica T Primožič Ines I Kovarik Zrinka Z

PloS one 20181005 10

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 ...[more]

PMID: 30289893

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