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Synthesis and biological evaluation of substituted acetamide derivatives as potential butyrylcholinestrase inhibitors.
- Source :
-
Scientific reports [Sci Rep] 2023 Mar 25; Vol. 13 (1), pp. 4877. Date of Electronic Publication: 2023 Mar 25. - Publication Year :
- 2023
-
Abstract
- Alzheimer's disease (AD) is the most common type of age-related dementia. Inhibition of butyrylcholinesterase (BChE) emerge as an effective therapeutic target for AD. A series of new substituted acetamide derivatives were designed, synthesized and evaluated for their ability to inhibit BChE. The bioassay results revealed that several compounds displayed attractive inhibition against BChE). Among them, compound 8c exhibited the highest BChE inhibition with IC <subscript>50</subscript> values of 3.94 μM. Lineweaver Burk plot indicated that 8c acted as a mixed-type BChE inhibitor. In addition, docking studies confirmed the results obtained through in vitro experiments, and showed that 8c bound to the catalytic anionic site (CAS) and peripheral anionic site (PAS) of BChE active site. Meanwhile, its ADME parameters were approximated using in silico method. Molecular dynamics simulation studies on the complex of 8c-BChE were performed, RMSD, RMSF, Rg, SASA, and the number of hydrogen bonds were calculated as well. These results implied that 8c could serve as appropriate lead molecule for the development of BChE inhibitor.<br /> (© 2023. The Author(s).)
- Subjects :
- Humans
Acetylcholinesterase metabolism
Molecular Docking Simulation
Cholinesterase Inhibitors chemistry
Amides therapeutic use
Acetamides pharmacology
Acetamides therapeutic use
Structure-Activity Relationship
Molecular Structure
Butyrylcholinesterase metabolism
Alzheimer Disease drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 13
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 36966194
- Full Text :
- https://doi.org/10.1038/s41598-023-31849-5