Tacrine-coumarin and Tacrine-7-chloroquinoline Hybrids with Thiourea Linkers: Cholinesterase Inhibition Properties, Kinetic Study, Molecular Docking and Permeability Assay for Blood-brain Barrier
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F18%3A50014989" target="_blank" >RIV/62690094:18470/18:50014989 - isvavai.cz</a>
Alternative codes found
RIV/00179906:_____/18:10382435 RIV/60162694:G44__/18:43889627
Result on the web
<a href="http://dx.doi.org/10.2174/1567205015666180711110750" target="_blank" >http://dx.doi.org/10.2174/1567205015666180711110750</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.2174/1567205015666180711110750" target="_blank" >10.2174/1567205015666180711110750</a>
Alternative languages
Result language
angličtina
Original language name
Tacrine-coumarin and Tacrine-7-chloroquinoline Hybrids with Thiourea Linkers: Cholinesterase Inhibition Properties, Kinetic Study, Molecular Docking and Permeability Assay for Blood-brain Barrier
Original language description
Background: The design of new heterodimeric dual binding site acetylcholinesterase inhibitors constitutes the main goal-directed to the development of new anticholinesterase agents with the expanded pharmacological profile. Multi-target compounds are usually designed by combining in a hybrid molecule with two or more pharmacophoric moieties that are known to enable interaction with the selected molecular targets.Methods: All compounds were tested for their inhibitory activity on human AChE/BChE. The Ellman's method was used to determine inhibition kinetics and IC50 values. In order to predict passive blood-brain penetration of novel compounds, modification of the parallel artificial membrane permeation assay has been used. Docking studies were performed in order to predict the binding modes of new hybrids with hAChE/hBChE respectively.Results: In this study, we described the design, synthesis, and evaluation of series tacrine-coumarin and tacrine-quinoline compounds which were found to show potential inhibition of ChEs and penetration of the blood-brain barrier.Conclusion: Tacrine-quinoline hybrids 7a exhibited the highest activity towards hBChE (IC50 = 0.97 tmol) and 7d towards hAChE (IC50 = 0.32 tmol). Kinetic and molecular modelling studies revealed that 7d was a mixed-type AChE inhibitor (K-i = 1.69 tmol) and 7a was a mixed-type BChE inhibitor (K-i = 1.09 mu mol). Moreover, hybrid 5d and 7c could penetrate the CNS.
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
30210 - Clinical neurology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2018
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Current Alzheimer research
ISSN
1567-2050
e-ISSN
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Volume of the periodical
15
Issue of the periodical within the volume
12
Country of publishing house
AE - UNITED ARAB EMIRATES
Number of pages
10
Pages from-to
1096-1105
UT code for WoS article
000448421000002
EID of the result in the Scopus database
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