PDF(Pubmed)
Abstract：
Alzheimer\'s disease (AD) is an age-related neurodegenerative disorder that is the leading cause of dementia in elderly individuals. Currently, there is no permanent treatment option available for this disorder, and the existing drug regimens are associated with limited effectiveness and side effects. To evaluate the neuroprotective effect of rosemary compounds, an extensive study was started with gas chromatography-mass spectrometry (GC-MS) analysis. GC-MS was performed to study the composition of rosemary essential oil and a total of 120 volatile compounds were identified. The 36 compounds from GC-MS data of rosemary essential oil having > 1% concentration in the oil were selected along with 3 already reported well-known non-volatile compounds of rosemary. se39 bioactive natural compounds of rosemary were docked against ACE, BACE1, GSK3, and TACE proteins, which are involved in AD progression. The top 3 compounds against each target protein were selected based on their binding energies and a total of 6 compounds were found as best candidates to target the AD; α Amyrin, Rosmanol, Androsta-1,4-dien-3-one,16,17-dihydroxy-(16.beta.,17.beta), Benzenesulfonamide,4-methyl-N-(5-nitro-2-pyridinyl), Methyl abietate, and Rosmarinic acid were the best compounds. The binding energy of α-Amyrin, Rosmanol, and Androsta-1,4-dien-3-one,16,17-dihydroxy-(16.beta.,17.beta) to ACE target is -10 kcal/mol, -9.3 kcal/mol, and - 9.3 kcal/mol, respectively. The best binding affinity was shown by complexes formed between GSK3-α-Amyrin (-9.1 kcal/mol), BACE1- α-Amyrin (-9.9 kcal/mol), and TACE- Benzenesulfonamide,4-methyl-N-(5-nitro-2-pyridinyl) (-9.1 kcal/mol). The comparative analysis between known inhibitors/ drugs of target proteins and the rosemary compound that shows the highest binding affinity against each protein also revealed the higher potential of rosemary natural compounds in terms of binding energy. The drug-likeliness properties like Lipinski\'s rule of five and the ADME/T analysis of top-selected compounds were screened through PkCSM and Deep-PK tools. The findings from this study suggested that rosemary compounds have the potential as a therapeutic lead for treating AD. This kind of experimental confirmation can lead to novel drug candidates against the pharmacological targets of AD.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s40203-024-00238-9.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s40203-024-00238-9.
摘要：
阿尔茨海默病（AD）是一种与年龄相关的神经退行性疾病，是老年人痴呆的主要原因。目前,这种疾病没有永久的治疗选择，和现有的药物方案与有限的有效性和副作用有关。为了评估迷迭香化合物的神经保护作用，从气相色谱-质谱（GC-MS）分析开始了广泛的研究。进行GC-MS以研究迷迭香精油的组成，并鉴定了总共120种挥发性化合物。选择来自GC-MS数据的在油中具有>1%浓度的迷迭香精油的36种化合物以及已经报道的迷迭香的3种熟知的非挥发性化合物。SE39迷迭香的生物活性天然化合物与ACE对接，BACE1、GSK3和TACE蛋白，与AD进展有关。根据其结合能选择针对每种靶蛋白的前3种化合物，总共6种化合物被发现是靶向AD的最佳候选物；αAmyrin，Rosmanol,Androsta-1,4-dien-3-one,16,17-二羟基-（16。beta。,17.beta),苯磺酰胺,4-甲基-N-(5-硝基-2-吡啶基),松香酸甲酯,迷迭香酸是最好的化合物。α-Amyrin的结合能,Rosmanol,和Androsta-1,4-dien-3-1,16,17-二羟基-（16。beta。,17.β)对ACE目标的影响为-10千卡/摩尔，-9.3千卡/摩尔，和-9.3千卡/摩尔，分别。GSK3-α-Amyrin（-9.1kcal/mol）之间形成的复合物显示出最佳的结合亲和力，BACE1-α-淀粉蛋白（-9.9千卡/摩尔），和TACE-苯磺酰胺，4-甲基-N-(5-硝基-2-吡啶基)(~9.1kcal/mol)。靶蛋白的已知抑制剂/药物与迷迭香化合物之间的比较分析显示出对每种蛋白的最高结合亲和力,也揭示了迷迭香天然化合物在结合能方面的更高潜力。通过PkCSM和Deep-PK工具筛选了诸如Lipinski的5法则和顶级选择化合物的ADME/T分析之类的药物相似特性。这项研究的结果表明，迷迭香化合物具有治疗AD的潜力。这类试验证实可以招致针对AD药理靶点的新型候选药物。
■在线版本包含补充材料，可在10.1007/s40203-024-00238-9获得。
■在线版本包含补充材料，可在10.1007/s40203-024-00238-9获得。
