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Synthesis and In Vitro Screening of Novel Heterocyclic β-d-Gluco- and β-d-Galactoconjugates as Butyrylcholinesterase Inhibitors


Baumann, Krešimir; Kordić, Lorena; Močibob, Marko; Šinko, Goran; Tomić, Srđanka
Synthesis and In Vitro Screening of Novel Heterocyclic β-d-Gluco- and β-d-Galactoconjugates as Butyrylcholinesterase Inhibitors // Molecules, 24 (2019), 15; 2833, 14 doi:10.3390/molecules24152833 (međunarodna recenzija, članak, znanstveni)


Naslov
Synthesis and In Vitro Screening of Novel Heterocyclic β-d-Gluco- and β-d-Galactoconjugates as Butyrylcholinesterase Inhibitors

Autori
Baumann, Krešimir ; Kordić, Lorena ; Močibob, Marko ; Šinko, Goran ; Tomić, Srđanka

Izvornik
Molecules (1420-3049) 24 (2019), 15; 2833, 14

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Anticholinesterase ; butyrylcholinesterase ; glucose ; galactose ; heterocycles

Sažetak
The development of selective butyrylcholinesterase (BChE) inhibitors may improve the treatment of Alzheimer’s disease by increasing lower synaptic levels of the neurotransmitter acetylcholine, which is hydrolysed by acetylcholinesterase, as well as by overexpressed BChE. An increase in the synaptic levels of acetylcholine leads to normal cholinergic neurotransmission and improved cognitive functions. A series of 14 novel heterocyclic β-d-gluco- and β-d-galactoconjugates were designed and screened for inhibitory activity against BChE. In the kinetic studies, 4 out of 14 compounds showed an inhibitory effect towards BChE, with benzimidazolium and 1-benzylbenzimidazolium substituted β-d-gluco- and β-d-galacto-derivatives in a 10–50 micromolar range. The analysis performed by molecular modelling indicated key residues of the BChE active site, which contributed to a higher affinity toward the selected compounds. Sugar moiety in the inhibitor should enable better blood–brain barrier permeability, and thus increase bioavailability in the central nervous system of these compounds.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Farmacija



POVEZANOST RADA


Projekt / tema
HRZZ-IP-2014-09-7899 - Sinteza, strukturna analiza i biološka evaluacija peptidomimetika i glikonjugata (Srđanka Tomić-Pisarović, )

Ustanove
Institut za medicinska istraživanja i medicinu rada, Zagreb,
Prirodoslovno-matematički fakultet, Zagreb

Časopis indeksira:


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


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