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Synthesis and neuroprotective activity of 3-aryl-3-azetidinyl acetic acid methyl ester derivatives.
- Source :
-
Archiv der Pharmazie [Arch Pharm (Weinheim)] 2023 Dec; Vol. 356 (12), pp. e2300378. Date of Electronic Publication: 2023 Oct 05. - Publication Year :
- 2023
-
Abstract
- 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.<br /> (© 2023 The Authors. Archiv der Pharmazie published by Wiley-VCH GmbH on behalf of Deutsche Pharmazeutische Gesellschaft.)
- Subjects :
- Humans
Butyrylcholinesterase metabolism
Acetylcholinesterase metabolism
Molecular Docking Simulation
Structure-Activity Relationship
Cholinesterase Inhibitors chemistry
Glutamates therapeutic use
Alzheimer Disease drug therapy
Neuroprotective Agents pharmacology
Neuroprotective Agents chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1521-4184
- Volume :
- 356
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Archiv der Pharmazie
- Publication Type :
- Academic Journal
- Accession number :
- 37797174
- Full Text :
- https://doi.org/10.1002/ardp.202300378