Asadipour Ali, Pourshojaei Yaghoub, Mansouri Moein, Mahdavizadeh Elham, Irajie Cambyz, Mottaghipisheh Javad, Faghih-Mirzaei Ehsan, Mahdavi Mohammad, Iraji Aida
Department of Medicinal Chemistry, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran.
Extremophile and Productive Microorganisms Research Center, Kerman University of Medical Sciences, Kerman, Iran.
BMC Chem. 2024 Apr 10;18(1):70. doi: 10.1186/s13065-024-01170-x.
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 (IC = 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 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.
在本文中，我们展示了氨基-7,8-二氢-4H-色原酮衍生物的设计与合成，这些衍生物可能作为乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BChE）的抑制剂，用于治疗阿尔茨海默病（AD）。对目标化合物进行了体外抗AChE和BChE评估，与用作阳性对照的多奈哌齐相比，4k对BChE表现出良好的活性（IC = 0.65 ± 0.13 µM）。动力学研究表明，化合物4k表现出竞争性抑制类型，K值为0.55 µM。分子对接和分子动力学模拟进一步支持了我们设计策略的合理性，因为4k与BChE的活性位点显示出有前景的结合相互作用。总体而言，我们的研究结果突出了氨基-7,8-二氢-4H-色原酮衍生物作为开发针对胆碱酯酶的新型疗法以治疗AD的有前景候选物的潜力。
