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Synthesis and neuroprotective activity of 3-aryl-3-azetidinyl acetic acid methyl ester derivatives
U. Šachlevičiūtė, G. Gonzalez, M. Kvasnicová, Š. Štěpánková, N. Kleizienė, A. Bieliauskas, M. Zatloukal, M. Strnad, FA. Sløk, M. Kvasnica, A. Šačkus, A. Žukauskaitė
Jazyk angličtina Země Německo
Typ dokumentu časopisecké články
Grantová podpora
Doctoral Fund of Kaunas University of Technology No. A-410, Approved 26 June 2019
Vipergen ApS
CZ.02.1.01/0.0/0.0/16_019/0000868
European Regional Development Fund
23-05389S
Czech Science Foundation
PubMed
37797174
DOI
10.1002/ardp.202300378
Knihovny.cz E-zdroje
- MeSH
- acetylcholinesterasa metabolismus MeSH
- Alzheimerova nemoc * farmakoterapie MeSH
- butyrylcholinesterasa metabolismus MeSH
- cholinesterasové inhibitory chemie MeSH
- glutamáty terapeutické užití MeSH
- lidé MeSH
- neuroprotektivní látky * farmakologie chemie MeSH
- simulace molekulového dockingu MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
A library of 3-aryl-3-azetidinyl acetic acid methyl ester derivatives was prepared from N-Boc-3-azetidinone employing the Horner-Wadsworth-Emmons reaction, rhodium(I)-catalyzed conjugate addition of arylboronic acids, and subsequent elaborations to obtain N-unprotected hydrochlorides, N-alkylated and N-acylated azetidine derivatives. The compounds were evaluated for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity, revealing several derivatives to possess AChE inhibition comparable to that of the AChE inhibitor rivastigmine. The binding mode of the AChE inhibitor donepezil and selected active compounds 26 and 27 within the active site of AChE was studied using molecular docking. Furthermore, the neuroprotective activity of the prepared compounds was evaluated in models associated with Parkinson's disease (salsolinol-induced) and aspects of Alzheimer's disease (glutamate-induced oxidative damage). Compound 28 showed the highest neuroprotective effect in both salsolinol- and glutamate-induced neurodegeneration models, and its protective effect in the glutamate model was revealed to be driven by a reduction in oxidative stress and caspase-3/7 activity.
Department of Chemical Biology Faculty of Science Palacký University Olomouc Czech Republic
Institute of Synthetic Chemistry Kaunas University of Technology Kaunas Lithuania
Citace poskytuje Crossref.org
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