螺喹唑啉化合物作为乙酰胆碱酯酶抑制剂防治阿尔茨海默病的硅学和 ADMET 研究。

Abdulelah Aljuaid, Osama Abdulaziz, Mamdouh Allahyani, Mazen Almehmadi, Abdullah Yahya Abdullah Alzahrani, Shivani Verma, Mohd Yusuf, Mohammad Asif
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引用次数: 0

摘要

背景:阿尔茨海默病(AD)是一种常见的神经退行性疾病,其特征是由于大脑神经元的变性和死亡而导致的进行性认知能力下降和记忆障碍。乙酰胆碱酯酶(AChE)抑制剂可调节对认知功能至关重要的乙酰胆碱水平,因此被用于多种神经退行性疾病的主要药物治疗。最近,喹唑啉衍生物作为一种引人注目的神经退行性疾病治疗模式出现了,并展示出良好的药理特性。它们独特的结构特征和药代动力学特征引发了人们对其在各种神经退行性疾病中潜在疗效和安全性的兴趣。喹唑啉衍生物作为一种潜在的治疗方法,强调了继续研究探索的必要性。喹唑啉衍生物具有多方面的作用机制,能够靶向与神经退行性病变有关的各种途径,为开发新型、有效、耐受性良好的治疗方法提供了令人振奋的前景。进一步研究喹唑啉衍生物的药理活性和确切的治疗作用,对于增进我们对神经退行性疾病病理生理学的了解和促进现代治疗策略的开发以应对这一严峻的医学挑战至关重要:喹唑啉衍生物具有显著的乙酰胆碱酯酶(AChE)抑制活性。喹唑啉衍生物能有效调节乙酰胆碱酯酶的活性,因此有望用于治疗神经系统疾病,尤其是阿尔茨海默病(AD)。它们错综复杂的分子结构赋予了对 AChE 的选择性和亲和性,为开发针对胆碱能通路的新型治疗药物提供了潜力。因此,在本研究中,我们设计、合成并表征了一系列螺[环卡拉烷-1,2'-喹唑啉衍生物(1-6),利用与活性位点的对接来评估它们可能的 AChE 抑制能力:结果:通过对 AChE 活性位点的对接研究,探讨了螺[环烷烃-1,2'-喹唑啉衍生物 (1-6) 的 AChE 抑制潜力。研究结果表明,这些衍生物具有明显的抑制活性,并凸显了其广阔的前景:结论:合成的螺[环烷-1,2'-喹唑啉衍生物(1-6)显示了其作为 AChE 抑制剂的显著潜力。观察到的明显抑制活性表明,这些衍生物值得进一步探索,以开发 AChE 抑制途径的候选治疗药物。这项研究强调了喹唑啉衍生物在寻找神经系统疾病(尤其是与胆碱能功能障碍有关的疾病)的新型治疗方法方面的相关性,它们可以成为一种有用的替代治疗剂。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
In Silico and ADMET Studies of Spiro-Quinazoline Compounds as Acetylcholine Esterase Inhibitors Against Alzheimer's Disease.

Background: Alzheimer's disease (AD) is a prevalent neurodegenerative condition characterized by progressive cognitive decline and memory impairment resulting from the degeneration and death of brain neurons. Acetylcholinesterase (AChE) inhibitors are used in primary pharmacotherapy for numerous neurodegenerative conditions, providing their capacity to modulate acetylcholine levels crucial for cognitive function. Recently, quinazoline derivatives have emerged as a compelling model for neurodegenerative disease treatment, showcasing promising pharmacological features. Their unique structural features and pharmacokinetic profiles have sparked interest in their potential efficacy and safety across diverse neurodegenerative disorders. The exposure of quinazoline derivatives as a potential therapeutic way underscores the imperative for continued research exploration. Their multifaceted mechanisms of action and ability to target various pathways implicated in neurodegeneration offer exciting prospects for developing novel, effective, and well-tolerated treatments. Further investigations into their pharmacological activities and precise therapeutic roles are essential to advance our understanding of neurodegenerative disease pathophysiology and promote the development of modern therapeutic strategies to address this critical medical challenge.

Methods: Quinazoline derivatives have gained eminent acetylcholinesterase (AChE) inhibitory activity. Their ability to effectively modulate AChE activity makes them promising candidates for treating neurological disorders, particularly Alzheimer's disease (AD). Their intricate molecular structures confer selectivity and affinity for AChE, offering potential for the development of novel therapeutic agents targeting cholinergic pathways. Hence, in this study, we designed, synthesized, and characterized a series of spiro[cycloalakane-1,2'-quinazoline derivatives (1-6) to assess their possible AChE inhibiting ability using docking into the active sites.

Results: The AChE inhibitory potential of spiro[cycloalkane-1,2'-quinazoline derivatives (1-6) was explored via docking studies of the AChE active site. The findings revealed significant inhibitory activity and highlighted the promising nature of these derivatives.

Conclusion: The synthesized spiro[cycloalkane-1,2'-quinazoline derivatives (1-6) exhibited their notable potential as AChE inhibitors. The observed significant inhibitory activity suggested that these derivatives warrant further exploration as candidates for developing therapeutic agents in AChE inhibitory pathways. This study emphasizes the relevance of quinazoline derivatives in searching for novel treatments for neurological disorders, particularly associated with cholinergic dysfunction, and they could be a useful alternative therapeutic agent.

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