DC pole | Wartość | Język |
dc.contributor.author | Pizova, Hana | - |
dc.contributor.author | Havelkova, Marketa | - |
dc.contributor.author | Stepankova, Sarka | - |
dc.contributor.author | Bąk, Andrzej | - |
dc.contributor.author | Kauerova, Tereza | - |
dc.contributor.author | Kozik, Violetta | - |
dc.contributor.author | Oravec, Michal | - |
dc.contributor.author | Imramovsky, Ales | - |
dc.contributor.author | Kollar, Peter | - |
dc.contributor.author | Bobal, Pavel | - |
dc.contributor.author | Jampilek, Josef | - |
dc.date.accessioned | 2019-04-06T12:32:52Z | - |
dc.date.available | 2019-04-06T12:32:52Z | - |
dc.date.issued | 2017 | - |
dc.identifier.citation | Molecules (Basel), 2017, iss. 11, art. no 1969 | pl_PL |
dc.identifier.issn | 1420-3049 | - |
dc.identifier.uri | http://hdl.handle.net/20.500.12128/8754 | - |
dc.description.abstract | Series of twenty-five benzyl (2S)-2-(arylcarbamoyl)pyrrolidine-1-carboxylates was prepared
and completely characterized. All the compounds were tested for their in vitro ability to
inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), and the selectivity of
compounds to individual cholinesterases was determined. Screening of the cytotoxicity of all
the compounds was performed using a human monocytic leukaemia THP-1 cell line, and the
compounds demonstrated insignificant toxicity. All the compounds showed rather moderate
inhibitory effect against AChE; benzyl (2S)-2-[(2-chlorophenyl)carbamoyl]pyrrolidine-1-carboxylate
(IC50 = 46.35 M) was the most potent agent. On the other hand, benzyl (2S)-2-[(4-bromophenyl)-] and
benzyl (2S)-2-[(2-bromophenyl)carbamoyl]pyrrolidine-1-carboxylates expressed anti-BChE activity
(IC50 = 28.21 and 27.38 M, respectively) comparable with that of rivastigmine. The ortho-brominated
compound as well as benzyl (2S)-2-[(2-hydroxyphenyl)carbamoyl]pyrrolidine-1-carboxylate
demonstrated greater selectivity to BChE. The in silico characterization of the structure–inhibitory
potency for the set of proline-based carbamates considering electronic, steric and lipophilic properties
was provided using comparative molecular surface analysis (CoMSA) and principal component
analysis (PCA). Moreover, the systematic space inspection with splitting data into the training/test
subset was performed to monitor the statistical estimators performance in the effort to map the
probability-guided pharmacophore pattern. The comprehensive screening of the AChE/BChE profile
revealed potentially relevant structural and physicochemical features that might be essential for
mapping of the carbamates inhibition efficiency indicating qualitative variations exerted on the
reaction site by the substituent in the 30-/40-position of the phenyl ring. In addition, the investigation
was completed by a molecular docking study of recombinant human AChE. | pl_PL |
dc.language.iso | en | pl_PL |
dc.rights | Uznanie autorstwa 3.0 Polska | * |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/pl/ | * |
dc.subject | proline | pl_PL |
dc.subject | carbamates | pl_PL |
dc.subject | in vitro cholinesterase inhibition | pl_PL |
dc.subject | in vitro cytotoxicity assay | pl_PL |
dc.subject | CoMSA | pl_PL |
dc.subject | IVE-PLS | pl_PL |
dc.subject | molecular docking study | pl_PL |
dc.title | Proline-based carbamates as cholinesterase inhibitors | pl_PL |
dc.type | info:eu-repo/semantics/article | pl_PL |
dc.relation.journal | Molecules (Basel) | pl_PL |
dc.identifier.doi | 10.3390/molecules22111969 | - |
Pojawia się w kolekcji: | Artykuły (WNŚiT)
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