N-alkylated tacrine derivatives as potential agents in Alzheimer's disease therapy
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F19%3A10394461" target="_blank" >RIV/00179906:_____/19:10394461 - isvavai.cz</a>
Alternative codes found
RIV/60162694:G44__/19:00536742 RIV/62690094:18470/19:50015597 RIV/00216208:11150/19:10394461 RIV/61988987:17110/19:A21026Z2
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=OuJ8bls4jX" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=OuJ8bls4jX</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.2174/1567205016666190314163942" target="_blank" >10.2174/1567205016666190314163942</a>
Alternative languages
Result language
angličtina
Original language name
N-alkylated tacrine derivatives as potential agents in Alzheimer's disease therapy
Original language description
Background: Based on the prevalence studies, the number of people suffering from dementia will almost double every 20 years, to 65.7 million in 2030 and 115.4 million in 2050, assuming no changes in mortality, effective preventative measures, definitive diagnostic guidelines or curative treatment. From the above-mentioned epidemiological data, it is obvious that dementia constitutes a major public health problem not only at present, but unfortunately also in the future. Objectives and Methods: Several N-alkylated tacrine (THA) derivatives have already been synthesized by Pomponi et al., in 1997. However, these compounds were tested for their anti-AChE activity using enzyme isolated from Electrophorus electricus. For this reason, we have decided to extend the previously reported series of THA derivatives and consequently test them in the battery of experiments, the results of which have served to more relevant evaluation of these compounds from the perspective of Alzeimer's disease compared to that published by Pomponi. Results and Conclusion: In summary, all compounds of interest effectively inhibited ChEs in vitro. One of the most promising derivatives 8 bearing an N-octyl chain showed 2.5-fold higher AChE inhibitory activity in relation to tacrine. With respect to blood-brain barrier (BBB) penetration, it can be claimed that synthesized analogues are presumably able to cross the BBB. From the point of view of hepatotoxicity, selected N-alkylated tacrine derivatives exerted worse results compared to tacrine. However, in vitro results are only illustrative, therefore, only in vivo experiments could determine the real value of selected N-alkylated THA derivatives.
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
30103 - Neurosciences (including psychophysiology)
Result continuities
Project
<a href="/en/project/GA16-08554S" target="_blank" >GA16-08554S: Novel hybrid compounds in the cognitive decline caused by neurodegeneration</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2019
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
16
Issue of the periodical within the volume
4
Country of publishing house
NL - THE KINGDOM OF THE NETHERLANDS
Number of pages
11
Pages from-to
333-343
UT code for WoS article
000465506200006
EID of the result in the Scopus database
2-s2.0-85066403647