Aljuaid Abdulelah, Abdulaziz Osama, Allahyani Mamdouh, Almehmadi Mazen, Alzahrani Abdullah Yahya Abdullah, Verma Shivani, Yusuf Mohd, Asif Mohammad
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Kingdom of Saudi Arabia.
Department of Chemistry, Faculty of Science and Arts, King Khalid University, Mohail Assir, Saudi Arabia.
CNS Neurol Disord Drug Targets. 2024 Oct 25. doi: 10.2174/0118715273315412241009092249.
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.
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.
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.
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.
阿尔茨海默病（AD）是一种常见的神经退行性疾病，其特征是由于脑神经元的退化和死亡导致进行性认知衰退和记忆障碍。乙酰胆碱酯酶（AChE）抑制剂被用于多种神经退行性疾病的一线药物治疗，因为它们能够调节对认知功能至关重要的乙酰胆碱水平。最近，喹唑啉衍生物已成为神经退行性疾病治疗的一个引人注目的模型，展现出有前景的药理学特性。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的潜在疗效和安全性的兴趣。将喹唑啉衍生物作为一种潜在的治疗方法进行研究凸显了持续深入探索的必要性。它们多方面的作用机制以及针对神经退行性变中涉及的各种途径的能力为开发新型、有效且耐受性良好的治疗方法提供了令人兴奋的前景。进一步研究它们的药理活性和确切治疗作用对于增进我们对神经退行性疾病病理生理学的理解以及推动应对这一关键医学挑战的现代治疗策略的发展至关重要。
喹唑啉衍生物已展现出显著的乙酰胆碱酯酶（AChE）抑制活性。它们有效调节AChE活性的能力使其成为治疗神经系统疾病，特别是阿尔茨海默病（AD）的有前景的候选药物。它们复杂的分子结构赋予了对AChE的选择性和亲和力，为开发针对胆碱能途径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[环烷烃 - 1,2'-喹唑啉]衍生物（1 - 6），通过对接至活性位点来评估它们可能的AChE抑制能力。
通过对AChE活性位点的对接研究探索了螺环[环烷烃 - 1,2'-喹唑啉]衍生物（1 - 6）的AChE抑制潜力。研究结果显示出显著的抑制活性，并突出了这些衍生物的前景。
合成的螺环[环烷烃 - 1,2'-喹唑啉]衍生物（1 - 6）展现出作为AChE抑制剂的显著潜力。观察到的显著抑制活性表明，这些衍生物作为AChE抑制途径中治疗药物的候选物值得进一步探索。本研究强调了喹唑啉衍生物在寻找神经系统疾病，特别是与胆碱能功能障碍相关疾病的新型治疗方法中的相关性，并且它们可能是一种有用的替代治疗药物。
