Novel neuroprotective 5,6-dihydropyrido[2′,1':2,3]imidazo[4,5-c] quinoline derivatives acting through cholinesterase inhibition and CB2 signaling modulation
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389030%3A_____%2F24%3A00601083" target="_blank" >RIV/61389030:_____/24:00601083 - isvavai.cz</a>
Alternative codes found
RIV/61989592:15110/24:73625290 RIV/61989592:15310/24:73625290 RIV/00216275:25310/24:39921852 RIV/00098892:_____/24:10158701
Result on the web
<a href="https://doi.org/10.1016/j.ejmech.2024.116592" target="_blank" >https://doi.org/10.1016/j.ejmech.2024.116592</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.ejmech.2024.116592" target="_blank" >10.1016/j.ejmech.2024.116592</a>
Alternative languages
Result language
angličtina
Original language name
Novel neuroprotective 5,6-dihydropyrido[2′,1':2,3]imidazo[4,5-c] quinoline derivatives acting through cholinesterase inhibition and CB2 signaling modulation
Original language description
A novel group of 5,6-dihydropyrido [2 ',1':2,3]imidazo [4,5-c]quinolines was prepared via a microwave assisted one-pot telescopic approach. The synthetic sequence involves the formation of an amine precursor of imidazo [1,2-a]pyridine via condensation and reduction under microwave irradiation. Subsequently, the Pictet-Spengler cyclisation reaction occurs with ketones (cyclic or acyclic) to obtain substituted 5,6-dihydropyrido [2 ',1':2,3] imidazo [4,5-c]quinolines in excellent yields. The compounds were tested as neuroprotective agents. Observed protection of neuron-like cells, SH-SY5Y differentiated with ATRA, in Parkinson's and Huntington's disease models inspired further mechanistic studies of protective activity against damage induced by 1-methyl-4-phenylpyridinium (MPP+), a compound causing Parkinson's disease. The novel compounds exhibit similar or higher potency than ebselen, an established drug with antioxidant activity, in the cells against MPP +induced total cellular superoxide production and cell death. However, they exhibit a significantly higher capacity to reduce mitochondrial superoxide and preserve mitochondrial membrane potential. We also observed marked differences between a selected derivative and ebselen in terms of normalizing MPP +induced phosphorylation of Akt and ERK1/2. The cytoprotective activity was abrogated when signaling through cannabinoid receptor CB2 was blocked. The compounds also inhibit both acetylcholine and butyrylcholine esterases. Overall the data show that novel 5,6-dihydropyrido [2 ',1':2,3]imidazo [4,5-c]quinoline have a broad cytoprotective activity which is mediated by several mechanisms including mitoprotection.
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
10608 - Biochemistry and molecular biology
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
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
European Journal of Medicinal Chemistry
ISSN
0223-5234
e-ISSN
1768-3254
Volume of the periodical
276
Issue of the periodical within the volume
OCT 5
Country of publishing house
NL - THE KINGDOM OF THE NETHERLANDS
Number of pages
15
Pages from-to
116592
UT code for WoS article
001271874400001
EID of the result in the Scopus database
2-s2.0-85198538522