Novel Drug Delivery Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Iran J Basic Med Sci. 2013 Oct;16(10):1049-54.
OBJECTIVE(S): Alzheimer's disease (AD) is a neurodegenerative disorder in elderly patients. Decrease in cholinergic neurotransmission is the main known cause in the pathophysiology of the disease. Improvement and potentiation of the cholinergic system could be beneficial for treatment of the AD. Acetylcholinesterase inhibitors such as donepezil can enhance the duration of action of acetylcholine (Ach) and therefore, through this mechanism improve the symptoms of AD.
In the current study, based on the potential inhibitory activity of phthalimide derivatives towards acetylcholinesterase enzyme, a new series of phthalimide-based compounds were synthesized (4a-4e) and anti-acetylcholinesterase effect was assessed using Ellman's test. Compound 4b with 4-Fluorophenyl moiety was the most potent derivative in this series (IC50 = 16.42 ± 1.07 µM). It was shown that, none of the synthesized compounds showed superior inhibitory potency compared to donepezil (0.41 ± 0.09 µM) as a reference drug.
The new synthesized phthalimide based analogs could function as potential acetylcholinesterase inhibitors. Further studies are necessary for development of potent analogs.
阿尔茨海默病（AD）是一种老年患者的神经退行性疾病。胆碱能神经传递的减少是疾病病理生理学的主要已知原因。改善和增强胆碱能系统可能有益于 AD 的治疗。乙酰胆碱酯酶抑制剂，如多奈哌齐，可以增强乙酰胆碱（Ach）的作用持续时间，因此通过这种机制可以改善 AD 的症状。
在本研究中，基于邻苯二甲酰亚胺衍生物对乙酰胆碱酯酶的潜在抑制活性，合成了一系列新的邻苯二甲酰亚胺类化合物（4a-4e），并使用 Ellman 试验评估了它们的抗乙酰胆碱酯酶作用。在该系列中，具有 4-氟苯基部分的化合物 4b 是最有效的衍生物（IC50=16.42±1.07µM）。结果表明，与作为参考药物的多奈哌齐（0.41±0.09µM）相比，没有一种合成化合物表现出更高的抑制活性。
新合成的邻苯二甲酰亚胺类类似物可以作为潜在的乙酰胆碱酯酶抑制剂。需要进一步的研究来开发有效的类似物。
