Simple view
Full metadata view
Authors
Statistics
Development of multifunctional, heterodimeric isoindoline-1,3-dione derivatives as cholinesterase and β-amyloid aggregation inhibitors with neuroprotective properties
Na publikacji autorka Szałaj Natalia podpisana jako Guzior Natalia.
The presented study describes the synthesis, pharmacological evaluation (AChE and BuChE inhibition, beta amyloid anti-aggregation effect and neuroprotective effect), molecular modeling and crystallographic studies of a novel series of isoindoline-1,3-dione derivatives. The target compounds were designed as dual binding site acetylcholinesterase inhibitors with an arylalkylamine moiety binding at the catalytic site of the enzyme and connected via an alkyl chain to a heterocyclic fragment, capable of binding at the peripheral anionic site of AChE. Among these molecules, compound 15b was found to be the most potent and selective AChE inhibitor (IC50EeAChE = 0.034 μM). Moreover, compound 13b in addition to AChE inhibition (IC50 EeAChE = 0.219 μM) possesses additional properties, such as the ability to inhibit Aβ aggregation (65.96% at 10 μM) and a neuroprotective effect against Aβ toxicity at 1 and 3 μM. Compound 13b emerges as a promising multi-target ligand for the further development of the therapy for age-related neurodegenerative disorders.
dc.abstract.en | The presented study describes the synthesis, pharmacological evaluation (AChE and BuChE inhibition, beta amyloid anti-aggregation effect and neuroprotective effect), molecular modeling and crystallographic studies of a novel series of isoindoline-1,3-dione derivatives. The target compounds were designed as dual binding site acetylcholinesterase inhibitors with an arylalkylamine moiety binding at the catalytic site of the enzyme and connected via an alkyl chain to a heterocyclic fragment, capable of binding at the peripheral anionic site of AChE. Among these molecules, compound 15b was found to be the most potent and selective AChE inhibitor (IC50EeAChE = 0.034 μM). Moreover, compound 13b in addition to AChE inhibition (IC50 EeAChE = 0.219 μM) possesses additional properties, such as the ability to inhibit Aβ aggregation (65.96% at 10 μM) and a neuroprotective effect against Aβ toxicity at 1 and 3 μM. Compound 13b emerges as a promising multi-target ligand for the further development of the therapy for age-related neurodegenerative disorders. | pl |
dc.affiliation | Wydział Farmaceutyczny : Zakład Fizykochemicznej Analizy Leku | pl |
dc.affiliation | Wydział Chemii : Zakład Krystalochemii i Krystalofizyki | pl |
dc.cm.id | 70304 | |
dc.contributor.author | Szałaj, Natalia - 140437 | pl |
dc.contributor.author | Bajda, Marek - 165281 | pl |
dc.contributor.author | Skrok, Mirosław | pl |
dc.contributor.author | Kurpiewska, Katarzyna - 142859 | pl |
dc.contributor.author | Lewiński, Krzysztof - 129948 | pl |
dc.contributor.author | Brus, Boris | pl |
dc.contributor.author | Pišlar, Anja | pl |
dc.contributor.author | Kos, Janko | pl |
dc.contributor.author | Gobec, Stanislav | pl |
dc.contributor.author | Malawska, Barbara - 130819 | pl |
dc.date.accessioned | 2015-07-02T10:15:22Z | |
dc.date.available | 2015-07-02T10:15:22Z | |
dc.date.issued | 2015 | pl |
dc.description.additional | Na publikacji autorka Szałaj Natalia podpisana jako Guzior Natalia. | pl |
dc.description.physical | 738-749 | pl |
dc.description.volume | 92 | pl |
dc.identifier.doi | 10.1016/j.ejmech.2015.01.027 | pl |
dc.identifier.eissn | 1768-3254 | pl |
dc.identifier.issn | 0223-5234 | pl |
dc.identifier.uri | http://ruj.uj.edu.pl/xmlui/handle/item/11196 | |
dc.language | eng | pl |
dc.language.container | eng | pl |
dc.rights.licence | Bez licencji otwartego dostępu | |
dc.subtype | Article | pl |
dc.title | Development of multifunctional, heterodimeric isoindoline-1,3-dione derivatives as cholinesterase and β-amyloid aggregation inhibitors with neuroprotective properties | pl |
dc.title.journal | European Journal of Medicinal Chemistry | pl |
dc.type | JournalArticle | pl |
dspace.entity.type | Publication |
* The migration of download and view statistics prior to the date of April 8, 2024 is in progress.
Views
16
Views per month
Views per city
No access