利用东莨菪碱小鼠痴呆模型评估氨基嘧啶衍生物的记忆增强作用

IF 2.9 3区 医学 Q2 NEUROSCIENCES
Behnaz Landi, Mona Khoramjouy, Alireza Ghavami Lahij, Sajjad Fazelkia, Salimeh Amidi, Farzad Kobarfard, Mehrdad Faizi
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引用次数: 0

摘要

近年来,氨基嘧啶类化合物由于其多靶点分子的出现,在药物发现领域获得了广泛的关注。这使他们成为认知能力提高的完美人选,因为认知能力下降是一个多方面的情况。我们的目标是评估它们增强记忆的潜力,特别是通过它们的胆碱能特性。本研究考察了七种氨基嘧啶衍生物的性质及其对记忆获得和保持的影响。这些化合物在东莨菪碱诱导健忘症后给予NMRI小鼠,并以药物多奈哌齐为阳性对照组,通过被动回避和自发交替试验评估记忆损伤和改善。这些化合物还通过对接和ADME预测研究进行分析,以确定与乙酰胆碱酯酶的潜在亲和力,并分别表征药代动力学性质。此外,体外抑制胆碱酯酶进行了评估。结果显示,在两项行为测试中,七种化合物中的三种显著提高了认知能力。软件分析表明,乙酰胆碱酯酶具有变构抑制或调节作用,这表明这些化合物具有进一步优化和最终用于治疗认知障碍病例的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Evaluation of the Memory Enhancement Effects of Aminopyrimidine Derivatives Using the Scopolamine Model of Dementia in Mice.

Aminopyrimidine compounds have been gaining traction in the field of drug discovery in recent years due to their emergence as multi-targeted molecules. This makes them perfect candidates as agents for cognitive improvement, as cognitive decline is a multifaceted condition. We aim to evaluate their potential for memory enhancement, specifically through their cholinergic properties. This work examines the properties of seven aminopyrimidine derivatives and their effects on memory acquisition and retention. These compounds were administered to NMRI mice after the induction of amnesia by scopolamine, and memory impairment and improvement were assessed using passive avoidance and spontaneous alternation tests with the drug donepezil as the positive control group. These compounds were also analyzed using docking and ADME prediction studies to determine potential affinity to the acetylcholinesterase enzyme, and characterize pharmacokinetic properties, respectively. Additionally, in vitro inhibition of cholinesterase was evaluated. Results showed that three of the seven compounds significantly increased cognition in both behavioral tests. Software analysis suggested allosteric inhibition or modulation of acetylcholinesterase, signifying the potential of these compounds for further optimization and eventual utilization for treatment of cognitive impairment cases.

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来源期刊
Neurotoxicity Research
Neurotoxicity Research 医学-神经科学
CiteScore
7.70
自引率
5.40%
发文量
164
审稿时长
6-12 weeks
期刊介绍: Neurotoxicity Research is an international, interdisciplinary broad-based journal for reporting both basic and clinical research on classical neurotoxicity effects and mechanisms associated with neurodegeneration, necrosis, neuronal apoptosis, nerve regeneration, neurotrophin mechanisms, and topics related to these themes. Published papers have focused on: NEURODEGENERATION and INJURY Neuropathologies Neuronal apoptosis Neuronal necrosis Neural death processes (anatomical, histochemical, neurochemical) Neurodegenerative Disorders Neural Effects of Substances of Abuse NERVE REGENERATION and RESPONSES TO INJURY Neural Adaptations Neurotrophin mechanisms and actions NEURO(CYTO)TOXICITY PROCESSES and NEUROPROTECTION Excitatory amino acids Neurotoxins, endogenous and synthetic Reactive oxygen (nitrogen) species Neuroprotection by endogenous and exogenous agents Papers on related themes are welcome.
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