Design, Synthesis, and Biological Evaluation of Novel Indanone Derivatives as Cholinesterase Inhibitors for Potential Use in Alzheimer's Disease.

Autor: Etemadi A; Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.; Department of Medicinal Chemistry, School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran., Hemmati S; Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran., Shahrivar-Gargari M; Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.; Pharmaceutical Analysis Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran., Abibiglue YT; Department of Medicinal Chemistry, School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran., Bavili A; Department of Medicinal Chemistry, School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran., Hamzeh-Mivehroud M; Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.; Department of Medicinal Chemistry, School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran., Dastmalchi S; Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.; Department of Medicinal Chemistry, School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.; Faculty of Pharmacy, Near East University, POBOX: 99138, Nicosia, Turkey.
Jazyk: angličtina
Zdroj: Chemistry & biodiversity [Chem Biodivers] 2023 Aug; Vol. 20 (8), pp. e202300075. Date of Electronic Publication: 2023 Jul 27.
DOI: 10.1002/cbdv.202300075
Abstrakt: Indanone derivatives containing meta/para-substituted aminopropoxy benzyl/benzylidene moieties were designed based on the structures of donepezil and ebselen analogs as the cholinesterase inhibitors. The designed compounds were synthesized and their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities were measured. Inhibitory potencies (IC 50 values) for the synthesized compounds ranged from 0.12 to 11.92 μM and 0.04 to 24.36 μM against AChE and BChE, respectively. Compound 5 c showed the highest AChE inhibitory potency with IC 50 value of 0.12 μM, whereas the highest BChE inhibition was achieved by structure 7 b (IC 50 =0.04 μM). Structure-activity relationship (SAR) analysis revealed that there is no significant difference between meta and para-substituted derivatives in AChE and BChE inhibition. However, the most potent AChE inhibitor 5 c belongs to meta-substituted compounds, while the most active BChE inhibitor is para-substituted derivative 7 b. The order of enzyme inhibition potency based on the substituted amine group is dimethyl amine>piperidine>morpholine. Compounds containing C=C linkage are more potent AChE inhibitors than the corresponding saturated structures. Molecular docking studies indicated that 5 c interacts with AChE in a very similar way to that observed experimentally for donepezil. The introduced indanone-aminopropoxy benzylidenes could be used in drug-discovery against Alzheimer's disease.
(© 2023 Wiley-VHCA AG, Zurich, Switzerland.)
Databáze: MEDLINE
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