Design, synthesis, and biological evaluation of 1-benzylamino-2-hydroxyalkyl derivatives as new potential disease-modifying multifunctional anti-Alzheimer's agents
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60162694%3AG44__%2F18%3A43889537" target="_blank" >RIV/60162694:G44__/18:43889537 - isvavai.cz</a>
Alternative codes found
RIV/00179906:_____/18:10375709
Result on the web
<a href="https://pubs.acs.org/doi/10.1021/acschemneuro.7b00461" target="_blank" >https://pubs.acs.org/doi/10.1021/acschemneuro.7b00461</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acschemneuro.7b00461" target="_blank" >10.1021/acschemneuro.7b00461</a>
Alternative languages
Result language
angličtina
Original language name
Design, synthesis, and biological evaluation of 1-benzylamino-2-hydroxyalkyl derivatives as new potential disease-modifying multifunctional anti-Alzheimer's agents
Original language description
The multitarget approach is a promising paradigm in drug discovery, potentially leading to new treatment options for complex disorders, such as Alzheimer's disease. Herein, we present the discovery of a unique series of 1-benzylamino-2-hydroxyalkyl derivatives combining inhibitory activity against butyrylcholinesterase, beta-secretase, amyloid, and tau protein aggregation, all related to mechanisms which underpin Alzheimer's disease. Notably, diphenylpropylamine derivative 10 showed balanced activity against both disease-modifying targets, inhibition of beta-secretase (IC50 hBACE-1 = 41.60 mu M), inhibition of amyloid beta aggregation (IC50, beta = 3.09 mu M), inhibition of tau aggregation (55% at 10 mu M); as well as against symptomatic targets, butyrylcholinesterase inhibition (IC50 (hBuchE) = 7.22 mu M). It might represent an encouraging starting point for development of multifunctional disease-modifying anti-Alzheimer's agents.
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
30104 - Pharmacology and pharmacy
Result continuities
Project
—
Continuities
N - Vyzkumna aktivita podporovana z neverejnych zdroju
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
ACS Chemical Neuroscience
ISSN
1948-7193
e-ISSN
—
Volume of the periodical
9
Issue of the periodical within the volume
5
Country of publishing house
US - UNITED STATES
Number of pages
21
Pages from-to
1074-1094
UT code for WoS article
000432752400021
EID of the result in the Scopus database
2-s2.0-85047190249