Department of Pharmaceutical Chemistry, Drug Analyses and Radiopharmacy, Faculty of Pharmacy, Medical University of Lodz, Lodz, Poland.
Department of Medicinal Chemistry, Faculty of Pharmacy, Medical University of Lublin, Lublin, Poland.
J Enzyme Inhib Med Chem. 2023 Dec;38(1):2158822. doi: 10.1080/14756366.2022.2158822.
Alzheimer's disease (AD) is a progressive neurodegenerative brain disease. Thus, drugs including donepezil, rivastigmine, and galantamine are not entirely effective in the treatment of this multifactorial disease. The present study evaluates eight derivatives (-) as candidates with stronger anti-AD potential but with less side effects. Reactive oxygen species (ROS) assays were used to assess oxidative stress which involve in the neurodegeneration. The neuroprotective properties of 3e against oxidative stress were done in three experiments using MTT test. The anti-AD potential was determined based on their anticholinesterase inhibition ability, determined using Ellman's method, Aβ aggregation potential according to thioflavin (Th) fluorescence assay, and their antioxidative and anti-inflammatory activities. Compound exhibited moderate cholinesterase inhibition activity (AChE, IC = 0.131 µM; BuChE, IC = 0.116 µM; SI = 1.13), significant inhibition of Aβ(1-42) aggregation (55.7%, at 5 µM) and acceptable neuroprotective activity. Extensive analysis of in vitro and in vivo assays indicates that new cyclopentaquinoline derivatives offer promise as candidates for new anti-AD drugs.
阿尔茨海默病（AD）是一种进行性神经退行性脑疾病。因此，包括多奈哌齐、加兰他敏和利伐斯的明在内的药物在治疗这种多因素疾病方面并非完全有效。本研究评估了八种（-）衍生物作为具有更强的抗 AD 潜力但副作用较小的候选药物。使用 MTT 试验在三个实验中进行了 3e 对氧化应激的神经保护特性研究，评估了涉及神经退行性变的活性氧（ROS）。根据噻唑（Th）荧光测定法，根据其对乙酰胆碱酯酶抑制能力（用 Ellman 法测定）、Aβ 聚集潜力和抗氧化和抗炎活性，确定了 3e 的抗 AD 潜力。化合物表现出中等的乙酰胆碱酯酶抑制活性（AChE，IC = 0.131 μM；BuChE，IC = 0.116 μM；SI = 1.13），对 Aβ（1-42）聚集的显著抑制作用（在 5 μM 时为 55.7%）和可接受的神经保护活性。体外和体内研究的广泛分析表明，新型环戊并喹啉衍生物具有作为新型抗 AD 药物候选物的潜力。
