Mirza Muhammad Usman, Mirza A Hammad, Ghori Noor-Ul-Huda, Ferdous Saba
Centre for Research in Molecular Medicine, The University of Lahore, Lahore, Pakistan.
Department of Bioscience, COMSATS Institute of Information Technology, Sahiwal, Pakistan.
Drug Des Devel Ther. 2014 Dec 18;9:187-98. doi: 10.2147/DDDT.S72794. eCollection 2015.
Parkinson's disease (PD) is caused by loss in nigrostriatal dopaminergic neurons and is ranked as the second most common neurodegenerative disorder. Dopamine receptor D3 is considered as a potential target in drug development against PD because of its lesser side effects and higher degree of neuro-protection. One of the prominent therapies currently available for PD is the use of dopamine agonists which mimic the natural action of dopamine in the brain and stimulate dopamine receptors directly. Unfortunately, use of these pharmacological therapies such as bromocriptine, apomorphine, and ropinirole provides only temporary relief of the disease symptoms and is frequently linked with insomnia, anxiety, depression, and agitation. Thus, there is a need for an alternative treatment that not only hinders neurodegeneration, but also has few or no side effects. Since the past decade, much attention has been given to exploitation of phytochemicals and their use in alternative medicine research. This is because plants are a cheap, indispensable, and never ending resource of active compounds that are beneficial against various diseases. In the current study, 40 active phytochemicals against PD were selected through literature survey. These ligands were docked with dopamine receptor D3 using AutoDock and AutoDockVina. Binding energies were compared to docking results of drugs approved by the US Food and Drug Administration against PD. The compounds were further analyzed for their absorption, distribution, metabolism, and excretion-toxicity profile. From the study it is concluded that glycyrrhetinic acid and E.resveratroloside are potent compounds having high binding energies which should be considered as potential lead compounds for drug development against PD.
帕金森病(PD)由黑质纹状体多巴胺能神经元缺失引起,是第二常见的神经退行性疾病。多巴胺受体D3因其副作用较小且神经保护程度较高,被认为是抗帕金森病药物研发的潜在靶点。目前治疗帕金森病的主要方法之一是使用多巴胺激动剂,这类药物可模拟多巴胺在大脑中的天然作用,直接刺激多巴胺受体。不幸的是,使用溴隐亭、阿扑吗啡和罗匹尼罗等药物治疗只能暂时缓解疾病症状,且常伴有失眠、焦虑、抑郁和激动等症状。因此,需要一种既能阻止神经退行性变,又几乎没有副作用的替代治疗方法。在过去十年中,植物化学物质的开发及其在替代医学研究中的应用受到了广泛关注。这是因为植物是一种廉价、不可或缺且源源不断的活性化合物来源,这些化合物对多种疾病有益。在本研究中,通过文献调研筛选出40种抗帕金森病的活性植物化学物质。使用AutoDock和AutoDockVina将这些配体与多巴胺受体D3进行对接。将结合能与美国食品药品监督管理局批准的抗帕金森病药物的对接结果进行比较。进一步分析这些化合物的吸收、分布、代谢和排泄毒性特征。研究得出结论,甘草次酸和白藜芦醇苷是具有高结合能的有效化合物,应被视为抗帕金森病药物研发的潜在先导化合物。