Novel multitarget-directed ligands aiming at symptoms and causes of Alzheimer's disease

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60162694%3AG44__%2F18%3A43889536" target="_blank" >RIV/60162694:G44__/18:43889536 - isvavai.cz</a>

Alternative codes found

RIV/00179906:_____/18:10375712

Result on the web

<a href="https://pubs.acs.org/doi/10.1021/acschemneuro.8b00024" target="_blank" >https://pubs.acs.org/doi/10.1021/acschemneuro.8b00024</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acschemneuro.8b00024" target="_blank" >10.1021/acschemneuro.8b00024</a>

Result language

angličtina

Original language name

Novel multitarget-directed ligands aiming at symptoms and causes of Alzheimer's disease

Original language description

Alzheimer&apos;s disease (AD) is a major public health problem, which is due to its increasing prevalence and lack of effective therapy or diagnostics. The complexity of the AD pathomechanism requires complex treatment, e.g. multifunctional ligands targeting both the causes and symptoms of the disease. Here, we present new multitarget-directed ligands combining pharmacophore fragments that provide a blockade of serotonin 5-HT(6 )receptors, acetyl/butyrylcholinesterase inhibition, and amyloid beta antiaggregation activity. Compound 12 has displayed balanced activity as an antagonist of 5-HT(6 )receptors (K-i= 18 nM) and noncompetitive inhibitor of cholinesterases (IC50hAChE = 14 nM, IC50eqBuChE = 22 nM). In further in vitro studies, compound 12 has shown amyloid beta antiaggregation activity (IC50 = 1.27 mu M) and ability to permeate through the blood-brain barrier. The presented findings may provide an excellent starting point for further studies and facilitate efforts to develop new effective anti-AD therapy.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30107 - Medicinal chemistry

Project

—

Continuities

N - Vyzkumna aktivita podporovana z neverejnych zdroju

Publication year

2018

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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

20

Pages from-to

1195-1214

UT code for WoS article

000432752400031

EID of the result in the Scopus database

2-s2.0-85047154588