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
Ali Asadipour,
Yaghoub Pourshojaei,
Moein Mansouri,
Elham Mahdavizadeh,
Cambyz Irajie,
Javad Mottaghipisheh,
Ehsan Faghih-Mirzaei,
Mohammad Mahdavi,
Aida Iraji
Affiliations
Ali Asadipour
Department of Medicinal Chemistry, Faculty of Pharmacy, Kerman University of Medical Sciences
Yaghoub Pourshojaei
Department of Medicinal Chemistry, Faculty of Pharmacy, Kerman University of Medical Sciences
Moein Mansouri
Department of Medicinal Chemistry, Faculty of Pharmacy, Kerman University of Medical Sciences
Elham Mahdavizadeh
Department of Medicinal Chemistry, Faculty of Pharmacy, Kerman University of Medical Sciences
Cambyz Irajie
Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences
Javad Mottaghipisheh
Department of Aquatic Sciences and Assessment, Swedish University of Agricultural Sciences
Ehsan Faghih-Mirzaei
Department of Medicinal Chemistry, Faculty of Pharmacy, Kerman University of Medical Sciences
Mohammad Mahdavi
Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences
Aida Iraji
Research Center for Traditional Medicine and History of Medicine, Department of Persian Medicine, School of Medicine, Shiraz University of Medical Sciences
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 K i 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.
