计算机预测β-咔啉生物碱哈尔明和哈尔碱可作为治疗帕金森病的潜在药物候选物。
In-silico Prediction of the Beta-carboline Alkaloids Harmine and Harmaline as Potent Drug Candidates for the Treatment of Parkinson's disease.
机构信息
Eminent College of Pharmaceutical Technology, Barasat, Kolkata, India.
National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, India.
出版信息
Antiinflamm Antiallergy Agents Med Chem. 2021;20(3):250-263. doi: 10.2174/1871523019999201111192344.
BACKGROUND
Parkinson's disease (PD) is a progressive neurodegenerative disease manifested by core symptoms of loss of motor control and postural instability. Loss of dopaminergic neurons is the cause of PD, thus enhancing dopamine level by pharmacological treatment is one of the key treatment strategies for PD. However, the limitations of current treatment strategies open the possibility of novel drug candidates for the treatment of PD.
OBJECTIVE
To investigate the anti-PD potential of Harmine and Harmaline. We aim to evaluate the therapeutic potential of Harmine and Harmaline by in-silico approaches; molecular docking, pharmacokinetic and Prediction of Activity Spectra for Substances (PASS) analysis were used for evaluating the therapeutic potential of Harmine and Harmaline and standard drug levodopa (L-DOPA).
METHODS
Auto dock vina was used for molecular docking of all three compounds against D2- and D3- dopamine receptors. The pharmacokinetics (PKs) and toxicity profile were predicted by pkCSM, and the pharmacological activity was predicted by PASS analysis.
RESULTS
Molecular docking showed a higher binding affinity of Harmine and Harmaline as compared to L-DOPA, and these results were supported by in-silico pharmacokinetic and toxicity profiling. Moreover, PASS analysis showed anti-PD activity of Harmine and Harmaline.
CONCLUSION
Harmine and Harmaline exhibit higher binding affinity towards D2- and D3- dopamine receptors compared to L-DOPA, and PKs and toxicity profile support their potential as drug candidates for PD therapy.
背景
帕金森病（PD）是一种进行性神经退行性疾病，表现为运动控制丧失和姿势不稳定等核心症状。多巴胺能神经元的丧失是 PD 的病因，因此通过药物治疗提高多巴胺水平是 PD 的关键治疗策略之一。然而，目前治疗策略的局限性为 PD 的治疗提供了新的候选药物的可能性。
目的
研究哈美林和哈马灵的抗 PD 潜力。我们旨在通过计算方法评估哈美林和哈马灵的治疗潜力；分子对接、药代动力学和预测物质活性谱（PASS）分析用于评估哈美林和哈马灵以及标准药物左旋多巴（L-DOPA）的治疗潜力。
方法
使用 AutoDock Vina 对所有三种化合物进行与 D2-和 D3-多巴胺受体的分子对接。使用 pkCSM 预测药代动力学（PKs）和毒性概况，使用 PASS 分析预测药理活性。
结果
分子对接显示哈美林和哈马灵与 L-DOPA 相比具有更高的结合亲和力，这些结果得到了计算药理学 PKs 和毒性分析的支持。此外，PASS 分析显示哈美林和哈马灵具有抗 PD 活性。
结论
与 L-DOPA 相比，哈美林和哈马灵对 D2-和 D3-多巴胺受体表现出更高的结合亲和力，PKs 和毒性概况支持它们作为 PD 治疗候选药物的潜力。
Zotero 插件