Search for multifunctional agents against Alzheimer’s disease among nonimidazole histamine H3 receptor ligands. In vitro and in vivo pharmacological evaluation and computational studies of piperazine derivatives
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023752%3A_____%2F19%3A43919919" target="_blank" >RIV/00023752:_____/19:43919919 - isvavai.cz</a>
Alternative codes found
RIV/00179906:_____/19:10396494
Result on the web
<a href="https://www.sciencedirect.com/science/article/abs/pii/S0045206819302287?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/abs/pii/S0045206819302287?via%3Dihub</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.bioorg.2019.103084" target="_blank" >10.1016/j.bioorg.2019.103084</a>
Alternative languages
Result language
angličtina
Original language name
Search for multifunctional agents against Alzheimer’s disease among nonimidazole histamine H3 receptor ligands. In vitro and in vivo pharmacological evaluation and computational studies of piperazine derivatives
Original language description
In the search for new treatments for complex disorders such as Alzheimer’s disease the Multi-Target-Directed Ligands represent a very promising approach. The aim of the present study was to identify multifunctional compounds among several series of non-imidazole histamine H3 receptor ligands, derivatives of 1-[2-thiazol-5-yl-(2-aminoethyl)]-4-n-propylpiperazine, 1-[2-thiazol-4-yl-(2-aminoethyl)]-4-n-propylpiperazine and 1-phenoxyalkyl-4-(amino)alkylopiperazine using in vitro and in vivo pharmacological evaluation and computational studies. Performed in vitro assays showed moderate potency of tested compounds against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Molecular modeling studies have revealed possible interactions between the active compounds and both AChE and BuChE as well as the human H3 histamine receptor. Computational studies showed the high drug-likeness of selected compounds with very good physicochemical profiles. The parallel artificial membrane permeation assay proved outstanding blood–brain barrier penetration in test conditions. The most promising compound, A12, chemically methyl(4-phenylbutyl){2-[2-(4-propylpiperazin-1-yl)-1,3-thiazol-5-yl]ethyl}amine, possesses good balanced multifunctional profile with potency toward studied targets - H3 antagonist activity (pA2 = 8.27), inhibitory activity against both AChE (IC50 = 13.96 μM), and BuChE (IC50 = 14.62 μM). The in vivo pharmacological studies revealed the anti-amnestic properties of compound A12 in the passive avoidance test on mice.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10401 - Organic chemistry
Result continuities
Project
<a href="/en/project/EF16_025%2F0007444" target="_blank" >EF16_025/0007444: PharmaBrain</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
Bioorganic Chemistry
ISSN
0045-2068
e-ISSN
—
Volume of the periodical
90
Issue of the periodical within the volume
September
Country of publishing house
NL - THE KINGDOM OF THE NETHERLANDS
Number of pages
14
Pages from-to
"Article Number: 103084"
UT code for WoS article
000479184600043
EID of the result in the Scopus database
—