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Amino-7,8-Dihydro-4H-Chromenone Derivatives As Potential Inhibitors of Acetylcholinesterase and Butyrylcholinesterase for Alzheimer’S Disease Management; in Vitro and in Silico Study Publisher



Asadipour A1 ; Pourshojaei Y1, 2 ; Mansouri M1 ; Mahdavizadeh E1 ; Irajie C3 ; Mottaghipisheh J4, 5 ; Faghihmirzaei E1 ; Mahdavi M6 ; Iraji A5, 7
Authors
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Authors Affiliations
  1. 1. Department of Medicinal Chemistry, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran
  2. 2. Extremophile and Productive Microorganisms Research Center, Kerman University of Medical Sciences, Kerman, Iran
  3. 3. Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
  4. 4. Department of Aquatic Sciences and Assessment, Swedish University of Agricultural Sciences, Uppsala, 75007, Sweden
  5. 5. Research Center for Traditional Medicine and History of Medicine, Department of Persian Medicine, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
  6. 6. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
  7. 7. Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

Source: BMC Chemistry Published:2024


Abstract

In this article, we present the design and synthesis of amino-7,8-dihydro-4H-chromenone derivatives as possible inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) for the management of Alzheimer’s disease (AD). The target compounds were evaluated against AChE and BChE in vitro, and 4k exhibited good potency against BChE (IC50 = 0.65 ± 0.13 µM) compared with donepezil used as a positive control. Kinetic studies revealed that compound 4k exhibited a competitive-type inhibition with a Ki value of 0.55 µM. Molecular docking and molecular dynamics simulations further supported the rationality of our design strategy, as 4k showed promising binding interactions with the active sites of BChE. Overall, our findings highlight the potential of amino-7,8-dihydro-4H-chromenone derivatives as promising candidates for developing novel therapeutics targeting cholinesterase in managing AD. © The Author(s) 2024.
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