Institute of Neurobiology, Bulgarian Academy of Sciences, Acad. G. Bonchev St., Block 23, 1113 Sofia, Bulgaria.
Department of Pharmacology, Toxicology, and Pharmacotherapy, Faculty of Pharmacy, Medical University, 9002 Varna, Bulgaria.
Molecules. 2022 Aug 25;27(17):5456. doi: 10.3390/molecules27175456.
Alzheimer's disease (AD) is a neurodegenerative disease associated with memory impairment and other central nervous system (CNS) symptoms. Two myrtenal-adamantane conjugates (MACs) showed excellent CNS potential against Alzheimer's models. Adamantane is a common pharmacophore for drug design, and myrtenal (M) demonstrated neuroprotective effects in our previous studies. The aim of this study is to evaluate the MACs' neuroprotective properties in dementia.
Scopolamine (Scop) was applied intraperitoneally in Wistar rats for 11 days, simultaneously with MACs or M as a referent, respectively. Brain acetylcholine esterase (AChE) activity, noradrenaline and serotonin levels, and oxidative brain status determination followed behavioral tests on memory abilities. Molecular descriptors and docking analyses for AChE activity center affinity were performed.
M derivatives have favorable physicochemical parameters to enter the CNS. Both MACs restored memory damaged by Scop, showing significant AChE-inhibitory activity in the cortex, in contrast to M, supported by the modeling analysis. Moderate antioxidant properties were manifested by glutathione elevation and catalase activity modulation. MACs also altered noradrenaline and serotonin content in the hippocampus.
For the first time, neuroprotective properties of two MACs in a rat dementia model were observed. They were stronger than the natural M effects, which makes the substances promising candidates for AD treatment.
阿尔茨海默病（AD）是一种与记忆障碍和其他中枢神经系统（CNS）症状相关的神经退行性疾病。两种薄荷烷-金刚烷缀合物（MACs）在阿尔茨海默病模型中表现出优异的中枢神经系统潜力。金刚烷是药物设计的常见药效团，而薄荷烷（M）在我们之前的研究中表现出神经保护作用。本研究旨在评估 MACs 在痴呆症中的神经保护特性。
腹腔内给予东莨菪碱（Scop），连续 11 天，同时给予 MACs 或 M 作为对照。脑乙酰胆碱酯酶（AChE）活性、去甲肾上腺素和 5-羟色胺水平以及氧化脑状态测定，随后进行记忆能力行为测试。进行了针对 AChE 活性中心亲和力的分子描述符和对接分析。
M 衍生物具有有利的物理化学参数，可进入中枢神经系统。两种 MACs 均能恢复 Scop 引起的记忆损伤，与 M 相反，在皮层中表现出显著的 AChE 抑制活性，这得到了建模分析的支持。通过增加谷胱甘肽和调节过氧化氢酶活性，表现出适度的抗氧化特性。MACs 还改变了海马中的去甲肾上腺素和 5-羟色胺含量。
首次观察到两种 MACs 在大鼠痴呆模型中的神经保护特性。它们比天然 M 效果更强，这使这些物质成为治疗 AD 的有前途的候选药物。
