Novel Sulfonamide-Based Carbamates as Selective Inhibitors of BChE
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216275%3A25310%2F21%3A39917742" target="_blank" >RIV/00216275:25310/21:39917742 - isvavai.cz</a>
Result on the web
<a href="https://www.mdpi.com/1422-0067/22/17/9447" target="_blank" >https://www.mdpi.com/1422-0067/22/17/9447</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.3390/ijms22179447" target="_blank" >10.3390/ijms22179447</a>
Alternative languages
Result language
angličtina
Original language name
Novel Sulfonamide-Based Carbamates as Selective Inhibitors of BChE
Original language description
A series of 14 target benzyl [2-(arylsulfamoyl)-1-substituted-ethyl]carbamates was prepared by multi-step synthesis and characterized. All the final compounds were tested for their ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in vitro, and the selectivity index (SI) was determined. Except for three compounds, all compounds showed strong preferential inhibition of BChE, and nine compounds were even more active than the clinically used rivastigmine. Benzyl {(2S)-1-[(2-methoxybenzyl)sulfamoyl]-4-methylpentan-2-yl}carbamate, benzyl {(2S)-1-[(4-chlorobenzyl)sulfamoyl]-4-methylpentan-2-yl}carbamate, and benzyl [(2S)-1-(benzylsulfamoyl)-4-methylpentan-2-yl]carbamate showed the highest BChE inhibition (IC50 = 4.33, 6.57, and 8.52 mu M, respectively), indicating that the last two derivatives had approximately 5-fold higher inhibitory activity against BChE than rivastigmine, and the first one was even 9-fold more effective than rivastigmine. In addition, the selectivity index was approx. 10 or 34, respectively. The process of carbamylation and reactivation of BChE was studied for the most active derivatives 5k, 5j. The detailed information about the mode of binding of these compounds to the active site of both BChE and AChE was obtained in a molecular modeling study. In this study, combined techniques (docking, molecular dynamic simulations, and QTAIM (quantum theory of atoms in molecules) calculations) were employed.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10401 - Organic chemistry
Result continuities
Project
<a href="/en/project/GA18-03847S" target="_blank" >GA18-03847S: Pseudopeptide proteasome inhibitors</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
International Journal of Molecular Sciences
ISSN
1661-6596
e-ISSN
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Volume of the periodical
22
Issue of the periodical within the volume
17
Country of publishing house
CH - SWITZERLAND
Number of pages
30
Pages from-to
9447
UT code for WoS article
000694302900001
EID of the result in the Scopus database
2-s2.0-85114049409