| Title : Design and evaluation of selective butyrylcholinesterase inhibitors based on Cinchona alkaloid scaffold - Bosak_2018_PLoS.One_13_e0205193 |
| Author(s) : Bosak A , Ramic A , Smidlehner T , Hrenar T , Primozic I , Kovarik Z |
| Ref : PLoS ONE , 13 :e0205193 , 2018 |
| 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. |
| ESTHER : Bosak_2018_PLoS.One_13_e0205193 |
| PubMedSearch : Bosak_2018_PLoS.One_13_e0205193 |
| PubMedID: 30289893 |
Bosak A, Ramic A, Smidlehner T, Hrenar T, Primozic I, Kovarik Z (2018)
Design and evaluation of selective butyrylcholinesterase inhibitors based on Cinchona alkaloid scaffold
PLoS ONE
13 :e0205193
Bosak A, Ramic A, Smidlehner T, Hrenar T, Primozic I, Kovarik Z (2018)
PLoS ONE
13 :e0205193