当前位置: X-MOL 学术Drug Des. Dev. Ther. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Computational and Pharmacological Investigation of (E)-2-(4-Methoxybenzylidene)Cyclopentanone for Therapeutic Potential in Neurological Disorders
Drug Design, Development and Therapy ( IF 4.8 ) Pub Date : 2020-09-07 , DOI: 10.2147/dddt.s234345
Sabah Farooq 1 , Arif-Ullah Khan 1 , Muhammad Shahid Iqbal 2
Affiliation  

Purpose: This study involved the computational and pharmacological evaluation of (E)-2-(4-methoxybenzylidene)cyclopentan-1-one (A2K10).
Methods: In silico studies were conducted through virtual screening. Morris water and Y-maze tests were conducted to evaluate Alzheimer’s disease. Acute epilepsy haloperidol,and hyperalgesia were used to calculate the epilepsy model, with Parkinson’s disease and mechanical allodynia at a dose of 1– 10 mg/kg in the mouse model.
Results: A2K10 exhibited the highest binding affinity against α7 nicotinic acetylcholine receptors (− 256.02 kcal/mol). A2K10 decreased escape latency in the Morris water test during different trials. In the Y-maze test, A2K10 dose-dependently increased spontaneous alteration behavior, with maximum effect of 75.5%± 0.86%. Furthermore, A2K10 delayed onset of pentylenetetrazole-induced myoclonic jerks and tonic–clonic seizures and decreased duration of tonic–clonic convulsions in mice, with maximum effect of 93.8± 5.30, 77.8± 2.91, and 12.9± 1.99 seconds, respectively. In the haloperidol-induced Parkinson’s disease model, A2K10 significantly prolonged hanging time and reduced tardive dyskinesia. Moreover, A2K10 extended latency in hot-plate hyperalgesia and increased the paw-withdrawal threshold in mechanical allodynia. In toxicity studies, no mortality was observed.
Conclusion: Overall, the results indicated that A2K10 has potential as an anti-Alzheimer’s, antiepileptic, antiparkinsonian, and analgesic therapeutic compound.

Keywords: computational pharmacology, anti-Alzheimer, antiepileptic, antiparkinsonism , analgesic


中文翻译:

(E)-2-(4-甲氧基亚苄基)环戊酮在神经系统疾病中的治疗潜力的计算和药理学研究

目的:本研究涉及 (E)-2-(4-methoxybenzylidene)cyclopentan-1-one (A2K10) 的计算和药理学评估。
方法:通过虚拟筛选进行计算机研究。进行莫里斯水和 Y 迷宫测试以评估阿尔茨海默病。用急性癫痫氟哌啶醇和痛觉过敏计算癫痫模型,小鼠模型中帕金森病和机械性异常性疼痛的剂量为1-10 mg/kg。
结果: A2K10 对 α 7表现出最高的结合亲和力烟碱型乙酰胆碱受体 (− 256.02 kcal/mol)。在不同的试验中,A2K10 降低了莫里斯水测试中的逃生潜伏期。在 Y 迷宫测试中,A2K10 剂量依赖性地增加自发改变行为,最大效应为 75.5%±0.86%。此外,A2K10 延迟了戊四唑引起的肌阵挛和强直-阵挛性癫痫发作,并缩短了小鼠强直-阵挛抽搐的持续时间,最大效果分别为 93.8±5.30、77.8±2.91 和 12.9±1.99 秒。在氟哌啶醇诱导的帕金森病模型中,A2K10 显着延长悬吊时间并减少迟发性运动障碍。此外,A2K10 延长了热板痛觉过敏的潜伏期并增加了机械异常性疼痛的缩爪阈值。在毒性研究中,没有观察到死亡率。
结论:总体而言,结果表明 A2K10 具有作为抗阿尔茨海默病、抗癫痫、抗帕金森病和镇痛治疗化合物的潜力。

关键词:计算药理学,抗阿尔茨海默病,抗癫痫药,抗帕金森病,镇痛药
更新日期:2020-09-08
down
wechat
bug