Design and evaluation of selective butyrylcholinesterase inhibitors based on Cinchona alkaloid scaffold.
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...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC6173406?pdf=render |
| _version_ | 1819099224859475968 |
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| author | Anita Bosak Alma Ramić Tamara Šmidlehner Tomica Hrenar Ines Primožič Zrinka Kovarik |
| author_facet | Anita Bosak Alma Ramić Tamara Šmidlehner Tomica Hrenar Ines Primožič Zrinka Kovarik |
| author_sort | Anita Bosak |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T00:43:29Z |
| format | Article |
| id | doaj.art-20c29f790a65481facfcc9745baaefa0 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T00:43:29Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-20c29f790a65481facfcc9745baaefa02022-12-21T18:44:37ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-011310e020519310.1371/journal.pone.0205193Design and evaluation of selective butyrylcholinesterase inhibitors based on Cinchona alkaloid scaffold.Anita BosakAlma RamićTamara ŠmidlehnerTomica HrenarInes PrimožičZrinka KovarikThis 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.http://europepmc.org/articles/PMC6173406?pdf=render |
| spellingShingle | Anita Bosak Alma Ramić Tamara Šmidlehner Tomica Hrenar Ines Primožič Zrinka Kovarik Design and evaluation of selective butyrylcholinesterase inhibitors based on Cinchona alkaloid scaffold. PLoS ONE |
| title | Design and evaluation of selective butyrylcholinesterase inhibitors based on Cinchona alkaloid scaffold. |
| title_full | Design and evaluation of selective butyrylcholinesterase inhibitors based on Cinchona alkaloid scaffold. |
| title_fullStr | Design and evaluation of selective butyrylcholinesterase inhibitors based on Cinchona alkaloid scaffold. |
| title_full_unstemmed | Design and evaluation of selective butyrylcholinesterase inhibitors based on Cinchona alkaloid scaffold. |
| title_short | Design and evaluation of selective butyrylcholinesterase inhibitors based on Cinchona alkaloid scaffold. |
| title_sort | design and evaluation of selective butyrylcholinesterase inhibitors based on cinchona alkaloid scaffold |
| url | http://europepmc.org/articles/PMC6173406?pdf=render |
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