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Pregled bibliografske jedinice broj: 954675

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


Bosak, Anita; Ramić, Alma; Šmidlehner, Tamara; Hrenar, Tomica; Primožič, Ines; Kovarik, Zrinka
Design and evaluation of selective butyrylcholinesterase inhibitors based on Cinchona alkaloid scaffold // PLoS One, 1 (2018), 1; 1-18 doi:10.1371/journal.pone.0205193 (međunarodna recenzija, članak, znanstveni)


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) 1 (2018), 1; 1-18

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



POVEZANOST RADA


Projekt / tema
HRZZ-IP-2013-11-4307 - Dizajn, sinteza i evaluacija novih protuotrova kod trovanja živčanim bojnim otrovima i pesticidima (Zrinka Kovarik, )
HRZZ-IP-2016-06-3775 - Aktivnošću i in silico usmjeren dizajn malih bioaktivnih molekula (Tomica Hrenar, )

Časopis indeksira:


  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE


Citati