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转铁蛋白包被的负载苯妥英的固体脂质纳米粒与癫痫分子靶点的计算机辅助分子对接和分子动力学模拟

In Silico molecular docking and molecular dynamic simulation of transferrin coated Phenytoin loaded SLNs with molecular targets of epilepsy.

作者信息

Zeb Ahmad, Ali Hussain, Khan Jehan Zeb, Shah Fawad Ali, Alattar Abdullah, Alanazi Fawaz E

机构信息

Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad Pakistan.

Department of Pharmacology and Toxicology, College of Pharmacy, Prince Sattam bin Abdulaziz University, Al-Kharj, Saudi Arabia.

出版信息

PLoS One. 2025 Jun 20;20(6):e0325772. doi: 10.1371/journal.pone.0325772. eCollection 2025.

DOI:10.1371/journal.pone.0325772
PMID:40540445
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12180723/
Abstract

Epilepsy is a chronic neurological disorder characterized by recurrent seizures, affecting millions of people worldwide. Phenytoin is a widely used antiepileptic drug, but its therapeutic efficacy is limited by poor brain penetration and undesirable side effects. We have investigated the drug against the selected candidate's protein target using Insilco analysis to check the mode of action in real time system. This makes Phenytoin a promising therapeutic drug for the management of different targets involved in Epilepsy disease. Considering this, using a wide range of computer aided drug-designing approaches, high interactions with the protein targets have been inferred against drug molecule Phenytoin. Eight receptors against Phenytoin molecules showed binding interactions during molecular docking but the top four i.e. Bcl-2, BDNF, IL-1β and Caspase showed high binding affinities with docking score of 7.8 kcal/mol, 7.7. kcal/mol. 7.4 kcal/mol and 7.1 kcal/mol respectively. The compound Phenytoin interacts with several important active side residues in the active domain of all the receptors which was further validated via molecular dynamic simulations for 100 ns time intervals. Furthermore, the complexes of Phenytoin reveal very stable dynamics with average RMSD, RMSF and ROG values with stable carbon-alpha atoms confirmation at different intervals. In conclusion, these molecules are promising and require experimental validation to prove them as epilepsy inhibitors.

摘要

癫痫是一种慢性神经疾病,其特征为反复发作的癫痫,全球数百万人受其影响。苯妥英是一种广泛使用的抗癫痫药物,但其治疗效果受到脑渗透率低和不良副作用的限制。我们使用计算机模拟分析针对选定候选蛋白靶点研究了该药物,以实时系统检查其作用模式。这使得苯妥英成为一种有望用于治疗癫痫疾病中不同靶点的治疗药物。考虑到这一点,使用多种计算机辅助药物设计方法,已推断出药物分子苯妥英与蛋白靶点具有高度相互作用。在分子对接过程中,针对苯妥英分子的八种受体显示出结合相互作用,但排名前四位的即Bcl-2、脑源性神经营养因子(BDNF)、白细胞介素-1β(IL-1β)和半胱天冬酶显示出高结合亲和力,对接分数分别为7.8千卡/摩尔、7.7千卡/摩尔、7.4千卡/摩尔和

7.1千卡/摩尔。化合物苯妥英与所有受体活性域中的几个重要活性侧链残基相互作用,这通过100纳秒时间间隔的分子动力学模拟得到进一步验证。此外,苯妥英的复合物显示出非常稳定的动力学,具有平均均方根偏差(RMSD)、均方根波动(RMSF)和回转半径(ROG)值,在不同时间间隔有稳定的碳α原子确认。总之,这些分子很有前景,需要进行实验验证以证明它们是癫痫抑制剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83a7/12180723/2eff9bb2b09b/pone.0325772.g009.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83a7/12180723/2eff9bb2b09b/pone.0325772.g009.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83a7/12180723/2eff9bb2b09b/pone.0325772.g009.jpg

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本文引用的文献

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Biomolecular mechanisms of epileptic seizures and epilepsy: a review.癫痫发作和癫痫的生物分子机制:综述
Acta Epileptol. 2023 Nov 15;5(1):28. doi: 10.1186/s42494-023-00137-0.
2
Epilepsy Treatment and Diagnosis Enhanced by Current Nanomaterial Innovations: A Comprehensive Review.当前纳米材料创新助力癫痫治疗与诊断:综述
Mol Neurobiol. 2025 Jan;62(1):946-961. doi: 10.1007/s12035-024-04328-9. Epub 2024 Jun 29.
3
Intranasal delivery of phenytoin loaded layered double hydroxide nanoparticles improves therapeutic effect on epileptic seizures.
鼻腔内递送达泊西酚负载层状双氢氧化物纳米颗粒可提高癫痫发作的治疗效果。
J Nanobiotechnology. 2024 Apr 2;22(1):144. doi: 10.1186/s12951-024-02405-8.
4
Adrenergic receptor system as a pharmacological target in the treatment of epilepsy (Review).肾上腺素能受体系统作为癫痫治疗的药理学靶点(综述)。
Med Int (Lond). 2024 Feb 27;4(2):20. doi: 10.3892/mi.2024.144. eCollection 2024 Mar-Apr.
5
NF-κB in biology and targeted therapy: new insights and translational implications.生物学与靶向治疗中的核因子-κB:新见解与转化意义
Signal Transduct Target Ther. 2024 Mar 4;9(1):53. doi: 10.1038/s41392-024-01757-9.
6
The role of HIF-1α/HO-1 pathway in hippocampal neuronal ferroptosis in epilepsy.缺氧诱导因子-1α/血红素加氧酶-1通路在癫痫海马神经元铁死亡中的作用
iScience. 2023 Sep 29;26(11):108098. doi: 10.1016/j.isci.2023.108098. eCollection 2023 Nov 17.
7
Solid Lipid Nanoparticles: Review of the Current Research on Encapsulation and Delivery Systems for Active and Antioxidant Compounds.固体脂质纳米粒:活性和抗氧化化合物包封与递送系统的当前研究综述
Antioxidants (Basel). 2023 Mar 3;12(3):633. doi: 10.3390/antiox12030633.
8
Surface-modified lipid nanocarriers for crossing the blood-brain barrier (BBB): A current overview of active targeting in brain diseases.表面修饰的脂质纳米载体穿越血脑屏障(BBB):脑疾病中主动靶向的最新综述。
Colloids Surf B Biointerfaces. 2023 Jan;221:112999. doi: 10.1016/j.colsurfb.2022.112999. Epub 2022 Nov 2.
9
Astrocytes in the initiation and progression of epilepsy.星形胶质细胞在癫痫的发生和发展中的作用。
Nat Rev Neurol. 2022 Dec;18(12):707-722. doi: 10.1038/s41582-022-00727-5. Epub 2022 Oct 24.
10
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Front Chem. 2022 Aug 17;10:908386. doi: 10.3389/fchem.2022.908386. eCollection 2022.